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Sample records for oxidized low-density lipoprotein-induced

  1. Oxidized low-density lipoprotein induces hematopoietic stem cell senescence.

    PubMed

    Zhang, Xian-Ping; Zhang, Gui-Hai; Wang, Yu-Ying; Liu, Jun; Wei, Qiang; Xu, Chun-Yan; Wang, Jian-Wei; Wang, Ya-Ping

    2013-09-01

    We have investigated oxidized low-density lipoprotein (ox-LDL) induced senescence in hematopoietic stem cells (HCs). Mouse Sca-1+ HCs were separated and purified using the magnetic activated cell sorting technique. Ox-LDL induced significant senescence in HCs measured by SA-β-Gal staining, and reduced CFU-Mix colony-forming capacity, arresting cells at G0/G1 phase. In agreement with the cell cycle arrest, ox-LDL markedly reduced the expression of CDK4, cyclin D, and cyclin E. As possible contributing factors for cell senescence, ox-LDL also induced cellular oxidative stress and reduced telomerase activity.

  2. Triolein and trilinolein ameliorate oxidized low-density lipoprotein-induced oxidative stress in endothelial cells.

    PubMed

    Luo, Ting; Deng, Ze-yuan; Li, Xiao-ping; Rao, Huan; Fan, Ya-wei

    2014-05-01

    Uptake of oxidized low-density lipoprotein by endothelial cells is a critical step for the initiation of atherosclerosis. Triacylglycerol uptake in these cells is understood to be a part of the process. The present investigation, comparison among the effects of simple acylglycerol, including tristearin, triolein, and trilinolein, upon oxidized low-density lipoprotein -induced oxidative stress was undertaken. Results indicated that trilinolein (78 % ± 0.02) and triolein (90 % ± 0.01) increased cell viability of endothelial cells exposed to oxidized low-density lipoprotein, whereas tristearin decreased the cell viability (55 % ± 0.03) (P < 0.05). Oxidized low-density lipoprotein treatment significantly increased apoptosis (23 %), compared to cells simultaneously exposed to trilinolein (19 %) or triolein (16 %), where apoptosis was reduced (P < 0.05). On the other hand, exposure to tristearin further increased oxidized low-density lipoprotein -induced cell apoptosis (34 %). Treatment with trilinolein or triolein on oxidized low-density lipoprotein -stimulated endothelial cells inhibited the expression of ICAM-1 and E-selectin mRNA. Moreover, both trilinolein and triolein demonstrated a strong antioxidant response to oxidative stress caused by oxidized low-density lipoprotein. Taken together, the results indicate trilinolein and triolein possess anti-inflammatory properties, which are mediated via the antioxidant defense system.

  3. Oxidized low-density lipoproteins induced inflammatory process during atherogenesis with aging

    NASA Astrophysics Data System (ADS)

    Larbi, Anis; Khalil, Abdelouahed; Douziech, Nadine; Guérard, Karl-Philippe; Fülöp, Tamàs

    2005-02-01

    Atherosclerosis is a chronic disease developing through decades with two life-threatening complications: myocardial infarction and stroke. Oxidized low-density lipoproteins (oxLDL) produced by oxidative modifications of LDL in the subendothelial space have been demonstrated to be critically involved in atherogenesis through their intensive pro-inflammatory activity. Recently, it was shown that oxLDL have an apoptosis-inducing effect in T cells depending on time and degree of oxidation. The goal of the current study is to elucidate the molecular mechanisms underlying the apoptotic-inducing effects of oxLDL on T lymphocytes. T cells of young and elderly subjects were incubated for various periods of time with LDL oxidized to various degrees. The proliferation, the apoptosis, the MAPK ERK1/2 activation and the expression of the Bcl-2 protein family members were measured upon different LDL treatments. Thus, more the LDL are oxidized more they induce apoptosis and this effect is highly accentuated with aging. The oxLDL decrease the activation of the surviving molecule ERK1/2 and modulate the ratio of Bax/Bcl-2 towards a pro-apoptotic profile, which is also accentuated with aging. These results partly explain why atherosclerosis is increasing with aging concomitantly to its complications.

  4. Protective effect of oleanolic acid on oxidized-low density lipoprotein induced endothelial cell apoptosis.

    PubMed

    Cao, Jianhua; Li, Guanghui; Wang, Meizhi; Li, Hui; Han, Zhiwu

    2015-10-01

    Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid, OA) is a naturally-occurring triterpenoid with various promising pharmacological properties. The present study was conducted to determine the protective effects of OA against oxidized low-density lipoprotein (ox-LDL) induced endothelial cell apoptosis and the possible underlying mechanisms. Our results showed that ox-LDL significantly decreased cell viability and induced apoptosis in human umbilical vein endothelial cells (HUVECs). OA in the co-treatment showed a protective effect against ox-LDL induced loss in cell viability and an increase in apoptosis, which was associated with the modulating effect of OA on ox-LDL induced hypoxia-inducible factor 1α(HIF-1α) expression. Moreover, our results showed that the modulating effect of OA against ox-LDL induced HIF-1α expression was obtained via inhibition of lipoprotein receptor 1 (LOX-1)/reactive oxygen species (ROS) signaling. Collectively, we suggested that the protective effect of OA against ox-LDL induced HUVEC apoptosis might, at least in part, be obtained via inhibition of the LOX-1/ROS/HIF-1α signaling pathway. PMID:26559024

  5. Rspo2 suppresses CD36-mediated apoptosis in oxidized low density lipoprotein-induced macrophages.

    PubMed

    Yan, Hui; Wang, Shuai; Li, Zhenwei; Sun, Zewei; Zan, Jie; Zhao, Wenting; Pan, Yanyun; Wang, Zhen; Wu, Mingjie; Zhu, Jianhua

    2016-10-01

    Oxidized low density lipoprotein (oxLDL)-induced apoptosis of macrophages contributes to the formation of atherosclerotic plaques. R‑spondin 2 (Rspo2), a member of the cysteine‑rich secreted proteins, has been shown to be involved in the oncogenesis of several types of cancer. It has also been found to be abundantly expressed among the four R‑spondin members in macrophages. The present study was performed to determine whether Rspo2 is involved in the ox‑LDL‑induced apoptosis of macrophages. It was identified that Rspo2 inhibited oxLDL‑induced apoptosis in the presence of endoplasmic reticulum (ER) stress activator using flow cytometry. In addition, Rspo2 was observed to suppress oxLDL‑induced ER stress and reactive oxygen species production as demonstrated by western blotting. Furthermore, analysis of the role of Rspo2 in macrophage lipid uptake identified that Rspo2 negatively regulated the Dil‑oxLDL uptake by inhibiting the expression of cluster of differentiation (CD)36, through the transcription factor, peroxisome proliferator‑activated receptor (PPAR)‑γ. The manipulation of Rspo2 had a direct effect on PPAR‑γ nuclear translocation. In addition, chromatin immunoprecipitation analysis revealed that Rspo2 manipulation led to regulation of the direct binding between PPAR‑γ and CD36. In conclusion, Rspo2 was found to have a negative regulatory effect during oxLDL‑induced macrophage apoptosis by regulating lipid uptake. PMID:27571704

  6. Protective effect of oleanolic acid on oxidized-low density lipoprotein induced endothelial cell apoptosis.

    PubMed

    Cao, Jianhua; Li, Guanghui; Wang, Meizhi; Li, Hui; Han, Zhiwu

    2015-10-01

    Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid, OA) is a naturally-occurring triterpenoid with various promising pharmacological properties. The present study was conducted to determine the protective effects of OA against oxidized low-density lipoprotein (ox-LDL) induced endothelial cell apoptosis and the possible underlying mechanisms. Our results showed that ox-LDL significantly decreased cell viability and induced apoptosis in human umbilical vein endothelial cells (HUVECs). OA in the co-treatment showed a protective effect against ox-LDL induced loss in cell viability and an increase in apoptosis, which was associated with the modulating effect of OA on ox-LDL induced hypoxia-inducible factor 1α(HIF-1α) expression. Moreover, our results showed that the modulating effect of OA against ox-LDL induced HIF-1α expression was obtained via inhibition of lipoprotein receptor 1 (LOX-1)/reactive oxygen species (ROS) signaling. Collectively, we suggested that the protective effect of OA against ox-LDL induced HUVEC apoptosis might, at least in part, be obtained via inhibition of the LOX-1/ROS/HIF-1α signaling pathway.

  7. Rspo2 suppresses CD36-mediated apoptosis in oxidized low density lipoprotein-induced macrophages

    PubMed Central

    Yan, Hui; Wang, Shuai; Li, Zhenwei; Sun, Zewei; Zan, Jie; Zhao, Wenting; Pan, Yanyun; Wang, Zhen; Wu, Mingjie; Zhu, Jianhua

    2016-01-01

    Oxidized low density lipoprotein (oxLDL)-induced apoptosis of macrophages contributes to the formation of atherosclerotic plaques. R-spondin 2 (Rspo2), a member of the cysteine-rich secreted proteins, has been shown to be involved in the oncogenesis of several types of cancer. It has also been found to be abundantly expressed among the four R-spondin members in macrophages. The present study was performed to determine whether Rspo2 is involved in the ox-LDL-induced apoptosis of macrophages. It was identified that Rspo2 inhibited oxLDL-induced apoptosis in the presence of endoplasmic reticulum (ER) stress activator using flow cytometry. In addition, Rspo2 was observed to suppress oxLDL-induced ER stress and reactive oxygen species production as demonstrated by western blotting. Furthermore, analysis of the role of Rspo2 in macrophage lipid uptake identified that Rspo2 negatively regulated the Dil-oxLDL uptake by inhibiting the expression of cluster of differentiation (CD)36, through the transcription factor, peroxisome proliferator-activated receptor (PPAR)-γ. The manipulation of Rspo2 had a direct effect on PPAR-γ nuclear translocation. In addition, chromatin immunoprecipitation analysis revealed that Rspo2 manipulation led to regulation of the direct binding between PPAR-γ and CD36. In conclusion, Rspo2 was found to have a negative regulatory effect during oxLDL-induced macrophage apoptosis by regulating lipid uptake. PMID:27571704

  8. [Oxidized low density lipoprotein induces macrophage endoplasmic reticulum stress via CD36.].

    PubMed

    Yao, Shu-Tong; Sang, Hui; Yang, Na-Na; Kang, Li; Tian, Hua; Zhang, Ying; Song, Guo-Hua; Qin, Shu-Cun

    2010-10-25

    The purpose of the present study is to explore the effect of oxidized low density lipoprotein (ox-LDL) on the induction of endoplasmic reticulum stress (ERS) and the underlying mechanisms in ox-LDL-induced macrophage foam-forming process. RAW264.7 macrophages were cultured in DMEM medium containing 10% fetal bovine serum, and then treated with ox-LDL (25, 50 and 100 mg/L), anti-CD36 monoclonal antibody+ox-LDL and tunicamycin (TM), respectively. After incubation for 24 h, the cells were collected. The cellular lipid accumulation was showed by oil red O staining and the content of cellular total cholesterol was quantified by enzymatic colorimetry. The expression of glucose-regulated protein 94 (GRP94), a molecular marker of ERS, was determined by immunocytochemistry assay. The levels of GRP94 protein, phosphorylated inositol-requiring enzyme 1 (p-IRE1) and X box binding protein 1 (XBP1) in RAW264.7 cells were detected by Western blotting. The results indicated that after incubation with ox-LDL (25, 50 and 100 mg/L) for 24 h, a large amount of lipid droplets were found in the cytoplasm, and the contents of cellular total cholesterol were increased by 2.1, 2.8 and 3.1 folds compared with the control, respectively. Anti-CD36 antibody decreased markedly the cellular lipid accumulation induced by ox-LDL at 100 mg/L. Both ox-LDL and TM, a specific ERS inducer, could up-regulate the protein expression of GRP94 in a dose-dependent manner. Furthermore, p-IRE1 and XBP1, two key components of the unfolded protein response, were also significantly induced by the treatment with ox-LDL. The up-regulations of the three proteins induced by ox-LDL were inhibited significantly when the macrophages were pre-incubated with anti-CD36 antibody. These results suggest that ox-LDL may induce ERS in a dose-dependent way and subsequently activate the unfolded protein response signaling pathway in RAW264.7 macrophages, which is potentially mediated by scavenger receptor CD36. PMID:20945046

  9. Oxidized low-density lipoprotein-induced apoptotic dendritic cells as a novel therapy for atherosclerosis.

    PubMed

    Frodermann, Vanessa; van Puijvelde, Gijs H M; Wierts, Laura; Lagraauw, H Maxime; Foks, Amanda C; van Santbrink, Peter J; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C A

    2015-03-01

    Modulation of immune responses may form a powerful approach to treat atherosclerosis. It was shown that clearance of apoptotic cells results in tolerance induction to cleared Ags by dendritic cells (DCs); however, this seems impaired in atherosclerosis because Ag-specific tolerance is lacking. This could result, in part, from decreased emigration of DCs from atherosclerotic lesions because of the high-cholesterol environment. Nonetheless, local induction of anti-inflammatory responses by apoptotic cell clearance seems to dampen atherosclerosis, because inhibition of apoptotic cell clearance worsens atherosclerosis. In this study, we assessed whether i.v. administration of oxLDL-induced apoptotic DCs (apop(ox)-DCs) and, as a control, unpulsed apoptotic DCs could modulate atherosclerosis by inducing tolerance. Adoptive transfer of apop(ox)-DCs into low-density lipoprotein receptor knockout mice either before or during feeding of a Western-type diet resulted in increased numbers of CD103(+) tolerogenic splenic DCs, with a concomitant increase in regulatory T cells. Interestingly, both types of apoptotic DCs induced an immediate 40% decrease in Ly-6C(hi) monocyte numbers and a 50% decrease in circulating CCL2 levels, but only apop(ox)-DC treatment resulted in long-term effects on monocytes and CCL2 levels. Although initial lesion development was reduced by 40% in both treatment groups, only apop(ox)-DC treatment prevented lesion progression by 28%. Moreover, progressed lesions of apop(ox)-DC-treated mice showed a robust 45% increase in collagen content, indicating an enhanced stability of lesions. Our findings clearly show that apoptotic DC treatment significantly decreases lesion development, but only apop(ox)-DCs can positively modulate lesion progression and stability. These findings may translate into a safe treatment for patients with established cardiovascular diseases using patient-derived apop(ox)-DCs.

  10. Oxidized low density lipoprotein receptor-1 mediates oxidized low density lipoprotein-induced apoptosis in human umbilical vein endothelial cells: role of reactive oxygen species.

    PubMed

    Chen, Xiu-ping; Xun, Ke-li; Wu, Qin; Zhang, Tian-tai; Shi, Jing-shan; Du, Guan-hua

    2007-07-01

    Studies have shown that oxidized low density lipoprotein (ox-LDL) elicits both necrotic and apoptotic cell death and several mechanisms have been proposed. Ox-LDL induces reactive oxygen species (ROS), a second messenger that might be involved in apoptosis, formation in different types of cells including endothelial cells (ECs) and smooth muscle cells (SMCs). As lectin-like ox-LDL receptor-1 (LOX-1) was the main receptor for ox-LDL, this study was designed to determine whether the apoptosis induced by ox-LDL was mediated by LOX-1 in cultured human umbilical vein endothelial cells (HUVECs) and whether there is an association between LOX-1 mediated apoptosis and the production of ROS. After exposure to ox-LDL (50,100, and 150 microg/ml for 18 h), HUVECs exhibit typical apoptotic characteristics as determined by transmission electron microscopy and flow cytometry analysis in a dose-dependent pattern. Ox-LDL increases intracellular ROS formation including superoxide anion (O2-) and hydrogen peroxide (H2O2) in a dose-dependent and time-dependent manner. Pretreatment with anti-LOX-1 mAb, Vitamin C, apocynin or catalase significantly reduced ROS production and prevented ox-LDL-induced apoptosis, while indomethacin or allopurinol had no effect. These results suggest that LOX-1 mediates ox-LDL-induced apoptosis in endothelial cells and that ROS production and NADPH oxidase might play an important role in ox-LDL-induced apoptosis.

  11. Glucose oxidation and low-density lipoprotein-induced macrophage ceroid accumulation: possible implications for diabetic atherosclerosis.

    PubMed Central

    Hunt, J V; Bottoms, M A; Clare, K; Skamarauskas, J T; Mitchinson, M J

    1994-01-01

    The exposure of proteins to high concentrations of glucose in vitro is widely considered a relevant model of the functional degeneration of tissue occurring in diabetes mellitus. In particular, the enhanced atherosclerosis in diabetes is often discussed in terms of glycation of low-density lipoprotein (LDL), the non-enzymic attachment of glucose to apolipoprotein amino groups. However, glucose can undergo transition-metal-catalysed oxidation under near-physiological conditions in vitro, producing oxidants that possess a reactivity similar to the hydroxyl radical. These oxidants can fragment protein, hydroxylate benzoic acid and induce lipid peroxidation in human LDL. In this study, glycation of LDL in vitro is accompanied by such oxidative processes. However, the oxidation of LDL varies with glucose concentration in a manner which does not parallel changes in protein glycation. Glycation increases in proportion to glucose concentration, whereas in our studies maximal oxidation occurs at a glucose concentration of approx. 25 mM. The modification of LDL resulting from exposure to glucose alters macrophage ceroid accumulation, a process which occurs in the human atherosclerotic plaque. The accumulation of ceroid in macrophages is shown to be related to LDL oxidation rather than LDL glycation, per se, as it too occurs at a maximum of approx. 25 mM. Oxidative sequelae of protein glycation appear to be a major factor in LDL-macrophage interactions, at least with respect to ceroid accumulation. Our observations are discussed in the context of the observed increase in the severity of atherosclerosis in diabetes. PMID:8198540

  12. Capsaicin protects endothelial cells and macrophage against oxidized low-density lipoprotein-induced injury by direct antioxidant action.

    PubMed

    Chen, Kuo-Shuen; Chen, Pei-Ni; Hsieh, Yih-Shou; Lin, Chin-Yin; Lee, Yi-Hsun; Chu, Shu-Chen

    2015-02-25

    Atherosclerosis is a chronic inflammatory vascular disease. It is characterized by endothelial dysfunction, lipid accumulation, leukocyte activation, and the production of inflammatory mediators and reactive oxygen species (ROS). Capsaicin, a biologically active compound of the red pepper and chili pepper, has several anti-oxidant, anti-inflammatory, anti-cancer, and hypolipidemic biological effects. However, its protective effects on foam cell formation and endothelial injury induced by oxidized low-density lipoprotein (oxLDL) remain unclear. In this study, we evaluated the anti-oxidative activity of capsaicin, and determined the mechanism by which capsaicin rescues human umbilical vein endothelial cells (HUVECs) from oxLDL-mediated dysfunction. The anti-oxidative activity of capsaicin was defined by Apo B fragmentation and conjugated diene production of the copper-mediated oxidation of LDL. Capsaicin repressed ROS generation, as well as subsequent mitochondrial membrane potential collapse, cytochrome c expression, chromosome condensation, and caspase-3 activation induced by oxLDL in HUVECs. Capsaicin also protected foam cell formation in macrophage RAW 264.7 cells. Our results suggest that capsaicin may prevent oxLDL-induced cellular dysfunction and protect RAW 264.7 cells from LDL oxidation. PMID:25603234

  13. Capsaicin protects endothelial cells and macrophage against oxidized low-density lipoprotein-induced injury by direct antioxidant action.

    PubMed

    Chen, Kuo-Shuen; Chen, Pei-Ni; Hsieh, Yih-Shou; Lin, Chin-Yin; Lee, Yi-Hsun; Chu, Shu-Chen

    2015-02-25

    Atherosclerosis is a chronic inflammatory vascular disease. It is characterized by endothelial dysfunction, lipid accumulation, leukocyte activation, and the production of inflammatory mediators and reactive oxygen species (ROS). Capsaicin, a biologically active compound of the red pepper and chili pepper, has several anti-oxidant, anti-inflammatory, anti-cancer, and hypolipidemic biological effects. However, its protective effects on foam cell formation and endothelial injury induced by oxidized low-density lipoprotein (oxLDL) remain unclear. In this study, we evaluated the anti-oxidative activity of capsaicin, and determined the mechanism by which capsaicin rescues human umbilical vein endothelial cells (HUVECs) from oxLDL-mediated dysfunction. The anti-oxidative activity of capsaicin was defined by Apo B fragmentation and conjugated diene production of the copper-mediated oxidation of LDL. Capsaicin repressed ROS generation, as well as subsequent mitochondrial membrane potential collapse, cytochrome c expression, chromosome condensation, and caspase-3 activation induced by oxLDL in HUVECs. Capsaicin also protected foam cell formation in macrophage RAW 264.7 cells. Our results suggest that capsaicin may prevent oxLDL-induced cellular dysfunction and protect RAW 264.7 cells from LDL oxidation.

  14. Oxidized Low Density Lipoprotein Induces Differentiation and Adhesion of Human Monocytes and the Monocytic Cell Line U937

    NASA Astrophysics Data System (ADS)

    Frostegard, Johan; Nilsson, Jan; Haegerstrand, Anders; Hamsten, Anders; Wigzell, Hans; Gidlund, Magnus

    1990-02-01

    Hypercholesterolemia is a major risk factor for development of atherosclerosis. In experimental animals fed a high-cholesterol diet, monocytes adhere to the arterial endothelium and penetrate into the intima where they differentiate into macrophages and ingest lipids thus giving rise to fatty streaks, the earliest type of atherosclerotic plaque. Macrophages express few receptors for normal low density lipo-protein (LDL) but can take up oxidized LDL by way of a scavenger receptor. The present study was designed to investigate the possible role of oxidized LDL in recruitment of resident intimal macrophages. We found that oxidized LDL induced enhanced expression of major histocompatibility complex class II molecules on human monocytes and U937 cells, a well-established system for studies of monocytic differentiation. Oxidized LDL also induced enhanced expression of the surface antigen LEuM3 but caused decreased expression of CD4 antigen, a pattern compatible with expression of a more differentiated macrophage-like phenotype. Oxidized LDL also initiated aggregation of monocytes and U937 cells and stimulated adhesion of U937 cells to cultured endothelial cells. The results indicate that oxidized LDL may contribute to development of atherosclerosis by inducing adhesion of monocytes to the arterial intima and by stimulating intimal monocytes to differentiate into resident macrophages.

  15. Ethanol extract of propolis protects endothelial cells from oxidized low density lipoprotein-induced injury by inhibiting lectin-like oxidized low density lipoprotein receptor-1-mediated oxidative stress.

    PubMed

    Fang, Yongqi; Li, Jinguo; Ding, Mingde; Xu, Xiaoyan; Zhang, Jiajun; Jiao, Peng; Han, Ping; Wang, Jiafu; Yao, Shutong

    2014-12-01

    Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), as the primary oxidized low-density lipoprotein (ox-LDL) receptor on endothelial cells, plays a crucial role in endothelial injury, which is a driving force in the initiation and development of atherosclerosis. Our previous studies have shown that ethanol extract of propolis (EEP) promotes reverse cholesterol transport and inhibits atherosclerotic lesion development. However, the protective effects of EEP against ox-LDL-induced injury in endothelial cells and the underlying mechanisms are still unknown. This study was designed to test the hypothesis that EEP attenuates ox-LDL-induced endothelial oxidative injury via modulation of LOX-1-mediated oxidative stress. Our results showed that exposure of human umbilical vein endothelial cells (HUVECs) to ox-LDL (100 mg/L) led to the decrease in cell viability and increase in lactate dehydrogenase (LDH) release, caspase-3 activation, and apoptosis, whereas pretreatment with EEP (7.5, 15 and 30 mg/L) protected against such damages in a dose-dependent manner. In addition, EEP mitigated ox-LDL uptake by HUVECs and attenuated ox-LDL-upregulated LOX-1 expression both at the mRNA and protein levels. Moreover, EEP suppressed the ox-LDL-induced oxidative stress as assessed by decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, reactive oxygen species (ROS), and malondialdehyde (MDA) generation as well as increased antioxidant enzyme activities. Similar results were observed in the anti-LOX-1 antibody or diphenyleneiodonium (DPI)-pretreated HUVECs. These data indicate that EEP may protect HUVECs from ox-LDL-induced injury and that the mechanism at least partially involves its ability to inhibit endothelial LOX-1 upregulation and subsequent oxidative stress.

  16. Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit

    SciTech Connect

    Guo Yanhong; Chen Kuanghueih; Gao Wei; Li Qian; Chen Li; Wang Guisong Tang Jian

    2007-11-16

    Our previous studies have implies that Mitofusin 2 (Mfn2), which was progressively reduced in arteries from ApoE{sup -/-} mice during the development of atherosclerosis, may take part in pathogenesis of atherosclerosis. In this study, we found that overexpression of Mfn2 inhibited oxidized low-density lipoprotein or serum induced vascular smooth muscle cell proliferation by down-regulation of Akt and ERK phosphorylation. Then we investigated the in vivo role of Mfn2 on the development of atherosclerosis in rabbits using adenovirus expressing Mitofusin 2 gene (AdMfn2). By morphometric analysis we found overexpression of Mfn2 inhibited atherosclerotic lesion formation and intima/media ratio by 66.7% and 74.6%, respectively, compared with control group. These results suggest that local Mfn2 treatment suppresses the development of atherosclerosis in vivo in part by attenuating the smooth muscle cell proliferation induced by lipid deposition and vascular injury.

  17. Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

    SciTech Connect

    Ou, Hsiu-Chung; Lee, Wen-Jane; Lee, Shin-Da; Huang, Chih-Yang; Chiu, Tsan-Hung; Tsai, Kun-Ling; Hsu, Wen-Cheng; Sheu, Wayne Huey-Herng

    2010-10-15

    Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized low-density lipoprotein (oxLDL) promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. Previous studies have shown that the phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase/nitric oxide (PI3K/Akt/eNOS/NO) pathway is involved in oxLDL-induced endothelial apoptosis. Ellagic acid, a natural polyphenol found in berries and nuts, has in recent years been the subject of intense research within the fields of cancer and inflammation. However, its protective effects against oxLDL-induced injury in vascular endothelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effect of ellagic acid in human umbilical vein endothelial cells (HUVECs) exposed to oxLDL and explored the possible mechanisms. Our results showed that pretreatment with ellagic acid (5-20 {mu}M) significantly attenuated oxLDL-induced cytotoxicity, apoptotic features, and generation of reactive oxygen species (ROS). In addition, the anti-apoptotic effect of ellagic acid was partially inhibited by a PI3K inhibitor (wortmannin) and a specific eNOS inhibitor (cavtratin) but not by an ERK inhibitor (PD98059). In exploring the underlying mechanisms of ellagic acid action, we found that oxLDL decreased Akt and eNOS phosphorylation, which in turn activated NF-{kappa}B and downstream pro-apoptotic signaling events including calcium accumulation, destabilization of mitochondrial permeability, and disruption of the balance between pro- and anti-apoptotic Bcl-2 proteins. Those alterations induced by oxLDL, however, were attenuated by pretreatment with ellagic acid. The inhibition of oxLDL-induced endothelial apoptosis by ellagic acid is due at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.

  18. Oxidized Low-Density Lipoprotein Induces Apoptosis in Cultured Neonatal Rat Cardiomyocytes by Modulating the TLR4/NF-κB Pathway

    PubMed Central

    Wang, Xiantao; Sun, Yuhan; Yang, Huafeng; Lu, Yuanxi; Li, Lang

    2016-01-01

    This study was designed to investigate the apoptosis induced by oxidized low-density lipoprotein (ox-LDL) in cultured neonatal rat cardiomyocytes and explore the possible mechanisms. We evaluated whether ox-LDL-induced apoptosis depended in part on the activation of toll-like receptor-4(TLR4)/Nuclear factor κB (NF-κB) signaling pathway. Cells were cultivated with and without ox-LDL. Cell apoptosis was evaluated by flow cytometry. Immunofluorescence, western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to assess protein or mRNA expressions. Resatorvid (TAK-242), an exogenous synthetic antagonist for TLR4, was used to inhibit TLR4 signal transduction. Dose- and time-dependent apoptotic index of cardiomyocytes occurred after ox-LDL treatment. Incubation of cardiomyocytes with ox-LDL (50 μg/mL) for 24 hours increased TLR4 and NF-κB expressions significantly. Decrease of Bcl-2/Bax protein ratio, activation of caspase-3 and 9 were also detected. Ox-LDL-induced cardiomyocyte apoptosis, TLR4 and NF-κB expressions were attenuated by pretreatment with TAK-242. In conclusion, our findings indicate that the apoptosis induced by ox-LDL in cultured neonatal rat cardiomyocytes at least in part by modulating the TLR4/NF-κB signaling pathway. PMID:27279424

  19. Danhong inhibits oxidized low-density lipoprotein-induced immune maturation of dentritic cells via a peroxisome proliferator activated receptor γ-mediated pathway.

    PubMed

    Liu, Hongying; Wang, Shijun; Sun, Aijun; Huang, Dong; Wang, Wei; Zhang, Chunyu; Shi, Dazhuo; Chen, Keji; Zou, Yunzeng; Ge, Junbo

    2012-01-01

    Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is effective in the treatment of atherosclerosis (AS)-related diseases. It is widely recognized that AS is a complex inflammatory disease of the arterial wall and the dendritic cells (DCs) is a major player in the pathogenesis of AS via mediating atherosclerotic antigen presenting and T lymphocytes. Here, we determined the effect and possible mechanism of DHI on oxidized low-density lipoprotein (ox-LDL)-induced maturation and immune function of DCs. Human monocyte-derived DCs were incubated with DHI or ciglitazone and were subsequently stimulated with ox-LDL to induce maturation. Similar to ciglitazone, a peroxisome proliferator activated receptor (PPAR) γ agonist, DHI, could significantly reduce ox-LDL-induced expressions of mature markers, enhance the endocytotic function, and inhibit secretions of cytokine on DCs. These effects of DHI could be partly reversed by silencing the PPARγ. In conclusion, DHI could inhibit ox-LDL-induced maturation of DCs partly through activating a PPARγ-mediated signaling pathway.

  20. Notoginsenoside R1 inhibits oxidized low-density lipoprotein induced inflammatory cytokines production in human endothelial EA.hy926 cells.

    PubMed

    Su, Ping; Du, Shijing; Li, Hang; Li, Zhi; Xin, Wenfeng; Zhang, Wensheng

    2016-01-01

    Notoginsenoside R1 (NG-R1), a unique and main active ingredient of Panax notoginseng, has been described to exhibit anti-inflammatory activity. However, its protective effects against oxidized low-density lipoprotein (oxLDL)-induced inflammatory injury in vascular endothelial cells have not been clarified. In the present study, we have evaluated the anti-inflammatory effects of NG-R1 on oxLDL-induced endothelial cells and its possible molecular mechanism of action. Our results showed that NG-R1 treatment significantly attenuated oxLDL-induced expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. These effects were accompanied with suppression of oxLDL-induced activation of NF-κB and Mitogen-activated protein kinases (MAPK). Moreover, NG-R1 also increased in Peroxisome proliferator-activated receptor γ (PPARγ) protein expression and transcription levels, and attenuated oxLDL-induced suppression of PPARγ expression. The inhibition of NG-R1 on oxLDL-induced TNF-α and IL-1β productions can be reversed by PPARγ antagonist GW9662. In conclusion, these data suggested that NG-R1 could suppress oxLDL-induced inflammatory cytokines production via activating PPARγ, which subsequently inhibiting oxLDL-induced NF-κB and MAPK activation.

  1. ORMDL3 contributes to the risk of atherosclerosis in Chinese Han population and mediates oxidized low-density lipoprotein-induced autophagy in endothelial cells.

    PubMed

    Ma, Xiaochun; Qiu, Rongfang; Dang, Jie; Li, Jiangxia; Hu, Qin; Shan, Shan; Xin, Qian; Pan, Wenying; Bian, Xianli; Yuan, Qianqian; Long, Feng; Liu, Na; Li, Yan; Gao, Fei; Zou, Chengwei; Gong, Yaoqin; Liu, Qiji

    2015-11-25

    ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) is a universally confirmed susceptibility gene for asthma and has recently emerged as a crucial modulator in lipid metabolism, inflammation and endoplasmic reticulum (ER) stress-the mechanisms also closely involved in atherosclerosis (AS). Here we first presented the evidence of two single nucleotide polymorphisms regulating ORMDL3 expression (rs7216389 and rs9303277) significantly associated with AS risk and the evidence of increased ORMDL3 expression in AS cases compared to controls, in Chinese Han population. Following the detection of its statistical correlation with AS, we further explored the functional relevance of ORMDL3 and hypothesized a potential role mediating autophagy as autophagy is activated upon modified lipid, inflammation and ER stress. Our results demonstrated that in endothelial cells oxidized low-density lipoprotein (ox-LDL) up-regulated ORMDL3 expression and knockdown of ORMDL3 alleviated not only ox-LDL-induced but also basal autophagy. BECN1 is essential for autophagy initiation and silencing of ORMDL3 suppressed ox-LDL-induced as well as basal BECN1 expression. In addition, deletion of ORMDL3 resulted in greater sensitivity to ox-LDL-induced cell death. Taken together, ORMDL3 might represent a causal gene mediating autophagy in endothelial cells in the pathogenesis of AS.

  2. ORMDL3 contributes to the risk of atherosclerosis in Chinese Han population and mediates oxidized low-density lipoprotein-induced autophagy in endothelial cells

    PubMed Central

    Ma, Xiaochun; Qiu, Rongfang; Dang, Jie; Li, Jiangxia; Hu, Qin; Shan, Shan; Xin, Qian; Pan, Wenying; Bian, Xianli; Yuan, Qianqian; Long, Feng; Liu, Na; Li, Yan; Gao, Fei; Zou, Chengwei; Gong, Yaoqin; Liu, Qiji

    2015-01-01

    ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) is a universally confirmed susceptibility gene for asthma and has recently emerged as a crucial modulator in lipid metabolism, inflammation and endoplasmic reticulum (ER) stress-the mechanisms also closely involved in atherosclerosis (AS). Here we first presented the evidence of two single nucleotide polymorphisms regulating ORMDL3 expression (rs7216389 and rs9303277) significantly associated with AS risk and the evidence of increased ORMDL3 expression in AS cases compared to controls, in Chinese Han population. Following the detection of its statistical correlation with AS, we further explored the functional relevance of ORMDL3 and hypothesized a potential role mediating autophagy as autophagy is activated upon modified lipid, inflammation and ER stress. Our results demonstrated that in endothelial cells oxidized low-density lipoprotein (ox-LDL) up-regulated ORMDL3 expression and knockdown of ORMDL3 alleviated not only ox-LDL-induced but also basal autophagy. BECN1 is essential for autophagy initiation and silencing of ORMDL3 suppressed ox-LDL-induced as well as basal BECN1 expression. In addition, deletion of ORMDL3 resulted in greater sensitivity to ox-LDL-induced cell death. Taken together, ORMDL3 might represent a causal gene mediating autophagy in endothelial cells in the pathogenesis of AS. PMID:26603569

  3. Overexpression of actin-depolymerizing factor blocks oxidized low-density lipoprotein-induced mouse brain microvascular endothelial cell barrier dysfunction.

    PubMed

    Wang, Jun; Sun, Lu; Si, Yan-Fang; Li, Bao-Min

    2012-12-01

    The aim of present work was to elucidate the role of actin-depolymerizing factor (ADF), an important regulator of actin cytoskeleton, in the oxidized low-density lipoprotein (ox-LDL)-induced blood-brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to ox-LDL. Treatment with LDL served as control. It was found that ADF mRNA level and protein expression were decreased when exposed to ox-LDL in MBMECs. Then, we investigated the influence of ADF overexpression on ox-LDL-treated MBMECs. Structurally, overexpression of ADF inhibited ox-LDL-induced F-actin formation. Functionally, overexpression of ADF attenuated ox-LDL-induced disruption of endothelial barrier marked by restoration of transendothelial electrical resistance, permeability of Evans Blue and expression of tight junction-associated proteins including ZO-1 and occludin, and blocked ox-LDL-induced oxidative stress marked by inhibition of reactive oxygen species (ROS) formation and activity of NADPH oxidase and Nox2 expression. However, overexpression of ADF in control cells had no significant effect on endothelial permeability and ROS formation. In conclusion, overexpression of ADF blocks ox-LDL-induced disruption of endothelial barrier. In addition, siRNA-mediated downregulation of ADF expression aggravated ox-LDL-induced disruption of endothelial barrier and ROS formation. These findings identify ADF as a key signaling molecule in the regulation of BBB integrity and suggest that ADF might be used as a target to modulate diseases accompanied by ox-LDL-induced BBB compromise.

  4. Oxidized low density lipoprotein induces bone morphogenetic protein-2 in coronary artery endothelial cells via Toll-like receptors 2 and 4.

    PubMed

    Su, Xin; Ao, Lihua; Shi, Yi; Johnson, Thomas R; Fullerton, David A; Meng, Xianzhong

    2011-04-01

    Vascular calcification is a common complication in atherosclerosis. Bone morphogenetic protein-2 (BMP-2) plays an important role in atherosclerotic vascular calcification. The aim of this study was to determine the effect of oxidized low density lipoprotein (oxLDL) on BMP-2 protein expression in human coronary artery endothelial cells (CAECs), the roles of Toll-like receptor (TLR) 2 and TLR4 in oxLDL-induced BMP-2 expression, and the signaling pathways involved. Human CAECs were stimulated with oxLDL. The roles of TLR2 and TLR4 in oxLDL-induced BMP-2 expression were determined by pretreatment with neutralizing antibody, siRNA, and overexpression. Stimulation with oxLDL increased cellular BMP-2 protein levels in a dose-dependent manner (40-160 μg/ml). Pretreatment with neutralizing antibodies against TLR2 and TLR4 or silencing of these two receptors reduced oxLDL-induced BMP-2 expression. Overexpression of TLR2 and TLR4 enhanced the cellular BMP-2 response to oxLDL. Furthermore, oxLDL was co-localized with TLR2 and TLR4. BMP-2 expression was associated with activation of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase (ERK)1/2. Inhibition of NF-κB and ERK1/2 reduced BMP-2 expression whereas inhibition of p38 MAPK had no effect. In conclusion, oxLDL induces BMP-2 expression through TLR2 and TLR4 in human CAECs. The NF-κB and ERK1/2 pathways are involved in the signaling mechanism. These findings underscore an important role for TLR2 and TLR4 in mediating the BMP-2 response to oxLDL in human CAECs and indicate that these two immunoreceptors contribute to the mechanisms underlying atherosclerotic vascular calcification. PMID:21325271

  5. Quercetin protects macrophages from oxidized low-density lipoprotein-induced apoptosis by inhibiting the endoplasmic reticulum stress-C/EBP homologous protein pathway.

    PubMed

    Yao, Shutong; Sang, Hui; Song, Guohua; Yang, Nana; Liu, Qinghua; Zhang, Ying; Jiao, Peng; Zong, Chuanlong; Qin, Shucun

    2012-07-01

    Quercetin (QUE), a member of the bioflavonoid family, has been proposed to have antioxidative, anti-inflammatory and antihypertensive properties. This study was designed to investigate the protective effect of QUE on oxidized low-density lipoprotein (ox-LDL)-induced cytotoxicity in RAW264.7 macrophages and specifically the endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP) pathway-mediated apoptosis. Our results showed that treatment with QUE (20, 40 and 80 μmol/L) significantly attenuated ox-LDL-induced cholesterol accumulation in macrophages and foam cell formation in a dose-dependent manner. Similar to tunicamycin (TM), a classical ER stress inducer, ox-LDL reduced cell viability and induced apoptosis in RAW264.7 macrophages. The cytotoxic effects of ox-LDL and TM were significantly inhibited by QUE treatment. Interestingly, we found that QUE also significantly suppressed the ox-LDL- and TM-induced activation of ER stress signaling events, including the phosphorylation of inositol-requiring enzyme 1 (IRE1), translocation of activating transcription factor 6 (ATF6) from the cytoplasm to the nucleus and upregulation of X-box-binding protein 1. In addition, exposure of RAW264.7 macrophages to ox-LDL or TM resulted in a significant increase in the expression of CHOP, a transcription factor regulated by IRE1 and ATF6 under conditions of ER stress, as well as a decrease in Bcl-2 transcript and protein concentrations. QUE blocked these effects in a dose-dependent manner. These data indicate that QUE can protect RAW264.7 cells from ox-LDL-induced apoptosis and that the mechanism at least partially involves its ability to inhibit the ER stress-CHOP signaling pathway.

  6. Paeonol suppresses oxidized low-density lipoprotein induced endothelial cell apoptosis via activation of LOX-1/p38MAPK/NF-κB pathway.

    PubMed

    Bao, Mei-Hua; Zhang, Yi-Wen; Zhou, Hong-Hao

    2013-03-27

    Paeonol is an active compound isolated from traditional Chinese medicine, and has been shown to have anti-atherosclerosis, anti-inflammatory, antioxidant effects. The present investigation was undertaken to determine the suppression effects of paeonol on oxidized low-density lipoprotein (ox-LDL) induced endothelial cell line HUVEC apoptosis and to uncover some of the underlying mechanisms of these effects. Cell viability and lactate dehydrogenase (LDH) were measured to evaluate the cell injuries. Apoptosis was evaluated by Hoechst 33342 staining and flow cytometry. Intracellular reactive oxygen species (ROS) generation was detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA). Real-time PCR was used to confirm the expression of LOX-1 mRNA. Western blotting was used to evaluate the protein expression of LOX-1 and Bcl-2, as well as caspase-3 cleavage, p38-mitogen-activated protein kinase (p38MAPK) phosphorylation. NF-κB nuclear translocation was detected by Western blotting and immunofluorescence. Caspase-3 activity was measured using a colorimetric protease assay kit. The results showed that ox-LDL significantly decreased cell viability and increased the LDH release, as well as the apoptotic rate (P<0.01). Pre-treatment of paeonol resulted in remarkable increase of cell viability, decrease of LDH release and cell apoptosis in a concentration-dependent manner. Besides, ox-LDL caused the up-regulation of LOX-1, the down-regulation of Bcl-2, the phosphorylation of p38MAPK, the translocation of NF-κB and the activation of caspase-3. Paeonol pre-treatment reversed these effects introduced by ox-LDL. Moreover, paeonol also showed its inhibition effects on ox-LDL induced ROS overproduction. These results indicate the preventive effects of paeonol on ox-LDL induced endothelial cell apoptosis. The effects might, at least partly, be obtained via inhibition of LOX-1-ROS- p38MAPK-NF-κB signaling pathway.

  7. L-cystathionine inhibits oxidized low density lipoprotein-induced THP-1-derived macrophage inflammatory cytokine monocyte chemoattractant protein-1 generation via the NF-κB pathway.

    PubMed

    Zhu, Mingzhu; Du, Junbao; Liu, Angie Dong; Holmberg, Lukas; Chen, Selena Y; Bu, Dingfang; Tang, Chaoshu; Jin, Hongfang

    2015-05-28

    This study aimed to explore whether and how L-cystathionine had any regulatory effect on the inflammatory response in THP-1-derived macrophages cultured in vitro under oxidized low-density lipoprotein (ox-LDL) stimulation. The human monocyte line THP-1 cell was cultured in vitro and differentiated into macrophages after 24 hours of PMA induction. Macrophages were pretreated with L-cystathionine and then treated with ox-LDL. The results showed that compared with the controls, ox-LDL stimulation significantly upregulated the expression of THP-1-derived macrophage MCP-1 by enhancing NF-κB p65 phosphorylation, nuclear translocation and DNA binding with the MCP-1 promoter. Compared with the ox-LDL group, 0.3 mmol/L and 1.0 mmol/L L-cystathionine significantly inhibited the expression of THP-1-derived macrophage MCP-1. Mechanistically, 0.3 mmol/L and 1.0 mmol/L L-cystathionine suppressed phosphorylation and nuclear translocation of the NF-κB p65 protein, as well as the DNA binding activity and DNA binding level of NF-κB with the MCP-1 promoter, which resulted in a reduced THP-1-derived macrophage MCP-1 generation. This study suggests that L-cystathionine could inhibit the expression of MCP-1 in THP-1-derived macrophages induced by ox-LDL via inhibition of NF-κB p65 phosphorylation, nuclear translocation, and binding of the MCP-1 promoter sequence after entry into the nucleus.

  8. Oxidized low-density lipoprotein induces apoptotic insults to mouse cerebral endothelial cells via a Bax-mitochondria-caspase protease pathway

    SciTech Connect

    Chen, T.-G.; Chen, T.-L.; Chang, H.-C.; Tai, Y.-T.; Cherng, Y.-G.; Chang, Y.-T.; Chen, R.-M. . E-mail: rmchen@tmu.edu.tw

    2007-02-15

    Cerebral endothelial cells (CECs) are crucial components of the blood-brain barrier. Oxidized low-density lipoprotein (oxLDL) can induce cell injuries. In this study, we attempted to evaluate the effects of oxLDL on mouse CECs and its possible mechanisms. Mouse CECs were isolated from brain tissues and identified by immunocytochemical staining of vimentin and Factor VIII. oxLDL was prepared from LDL oxidation by copper sulfate. Exposure of mouse CECs to oxLDL decreased cell viability in concentration- and time-dependent manners. oxLDL time-dependently caused shrinkage of cell morphologies. Administration of oxLDL to CECs induced DNA fragmentation in concentration- and time-dependent manners. Analysis of the cell cycle revealed that oxLDL concentration- and time-dependently increased the proportion of CECs which underwent apoptosis. Analysis of confocal microscopy and immunoblot revealed that oxLDL significantly increased cellular and mitochondrial Bax levels as well as the translocation of this proapoptotic protein from the cytoplasm to mitochondria. In parallel with the increase in the levels and translocation of Bax, oxLDL time-dependently decreased the mitochondrial membrane potential. Exposure of mouse CECs to oxLDL decreased the amounts of mitochondrial cytochrome c, but enhanced cytosolic cytochrome c levels. The amounts of intracellular reactive oxygen species were significantly augmented after oxLDL administration. Sequentially, oxLDL increased activities of caspase-9, -3, and -6 in time-dependent manners. Pretreatment with Z-VEID-FMK, an inhibitor of caspase-6, significantly decreased caspase-6 activity and the oxLDL-induced DNA fragmentation and cell apoptosis. This study showed that oxLDL induces apoptotic insults to CECs via signal-transducing events, including enhancing Bax translocation, mitochondrial dysfunction, cytochrome c release, increases in intracellular reactive oxygen species, and cascade activation of caspase-9, -3, and -6. Therefore, ox

  9. Oxidized low-density lipoprotein induces apoptotic insults to mouse cerebral endothelial cells via a Bax-mitochondria-caspase protease pathway.

    PubMed

    Chen, Tyng-Guey; Chen, Ta-Liang; Chang, Huai-Chia; Tai, Yu-Ting; Cherng, Yih-Giun; Chang, Ya-Ting; Chen, Ruei-Ming

    2007-02-15

    Cerebral endothelial cells (CECs) are crucial components of the blood-brain barrier. Oxidized low-density lipoprotein (oxLDL) can induce cell injuries. In this study, we attempted to evaluate the effects of oxLDL on mouse CECs and its possible mechanisms. Mouse CECs were isolated from brain tissues and identified by immunocytochemical staining of vimentin and Factor VIII. oxLDL was prepared from LDL oxidation by copper sulfate. Exposure of mouse CECs to oxLDL decreased cell viability in concentration- and time-dependent manners. oxLDL time-dependently caused shrinkage of cell morphologies. Administration of oxLDL to CECs induced DNA fragmentation in concentration- and time-dependent manners. Analysis of the cell cycle revealed that oxLDL concentration- and time-dependently increased the proportion of CECs which underwent apoptosis. Analysis of confocal microscopy and immunoblot revealed that oxLDL significantly increased cellular and mitochondrial Bax levels as well as the translocation of this proapoptotic protein from the cytoplasm to mitochondria. In parallel with the increase in the levels and translocation of Bax, oxLDL time-dependently decreased the mitochondrial membrane potential. Exposure of mouse CECs to oxLDL decreased the amounts of mitochondrial cytochrome c, but enhanced cytosolic cytochrome c levels. The amounts of intracellular reactive oxygen species were significantly augmented after oxLDL administration. Sequentially, oxLDL increased activities of caspase-9, -3, and -6 in time-dependent manners. Pretreatment with Z-VEID-FMK, an inhibitor of caspase-6, significantly decreased caspase-6 activity and the oxLDL-induced DNA fragmentation and cell apoptosis. This study showed that oxLDL induces apoptotic insults to CECs via signal-transducing events, including enhancing Bax translocation, mitochondrial dysfunction, cytochrome c release, increases in intracellular reactive oxygen species, and cascade activation of caspase-9, -3, and -6. Therefore, ox

  10. Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells.

    PubMed

    Hao, Shuangying; Ji, Jiajie; Zhao, Hongting; Shang, Longcheng; Wu, Jing; Li, Huihui; Qiao, Tong; Li, Kuanyu

    2015-12-01

    Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of the Szeto-Schiller (SS) peptides shown to specifically target the inner mitochondrial membrane to scavenge reactive oxygen species. In this study, we investigated whether SS-31 may provide protective effect on macrophage from foam cell formation in RAW264.7 cells. The results showed that SS-31 inhibited oxidized low-density lipoproteins (ox-LDL)-induced foam cell formation and cholesterol accumulation, demonstrated by intracellular oil red O staining and measurement of cholesterol content. The mechanism was revealed that SS-31 did not only significantly attenuated ox-LDL-induced generation of reactive oxygen species (ROS) and increased the activities of superoxide dismutases, but also dose-dependently inhibited the expression of CD36 and LOX-1, two scavenger receptors of ox-LDL, while the expression of ATP-binding cassette A1 and G1, playing a pivotal role in cholesterol efflux, was not affected. As a result, SS-31 decreased pro-inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, suggesting the prevention of inflammatory responses. In conclusion, our results demonstrate that SS-31 provides a beneficial effect on macrophages from foam cell formation, likely, through both ROS scavenging and inhibition of cholesterol influx. Therefore, SS-31 may potentially be of therapeutic relevance in prevention of human atherogenesis.

  11. Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells.

    PubMed

    Hao, Shuangying; Ji, Jiajie; Zhao, Hongting; Shang, Longcheng; Wu, Jing; Li, Huihui; Qiao, Tong; Li, Kuanyu

    2015-01-01

    Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of the Szeto-Schiller (SS) peptides shown to specifically target the inner mitochondrial membrane to scavenge reactive oxygen species. In this study, we investigated whether SS-31 may provide protective effect on macrophage from foam cell formation in RAW264.7 cells. The results showed that SS-31 inhibited oxidized low-density lipoproteins (ox-LDL)-induced foam cell formation and cholesterol accumulation, demonstrated by intracellular oil red O staining and measurement of cholesterol content. The mechanism was revealed that SS-31 did not only significantly attenuated ox-LDL-induced generation of reactive oxygen species (ROS) and increased the activities of superoxide dismutases, but also dose-dependently inhibited the expression of CD36 and LOX-1, two scavenger receptors of ox-LDL, while the expression of ATP-binding cassette A1 and G1, playing a pivotal role in cholesterol efflux, was not affected. As a result, SS-31 decreased pro-inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, suggesting the prevention of inflammatory responses. In conclusion, our results demonstrate that SS-31 provides a beneficial effect on macrophages from foam cell formation, likely, through both ROS scavenging and inhibition of cholesterol influx. Therefore, SS-31 may potentially be of therapeutic relevance in prevention of human atherogenesis. PMID:26633327

  12. XJP-1 protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by inhibiting NADPH oxidase subunit expression and modulating the PI3K/Akt/eNOS pathway.

    PubMed

    Fu, Rong; Wang, Qiujuan; Guo, Qinglong; Xu, Jinyi; Wu, Xiaoming

    2013-01-01

    Endothelial apoptosis triggered by oxidized low-density lipoprotein (ox-LDL) can accelerate the progression of endothelial dysfunction in atherosclerosis. (±)7,8-Dihydroxy-3-methyl-isochromanone-4 (XJP-1) is a natural phenolic compound derived from banana peel. In the present study, we investigated the anti-apoptotic effect of XJP-1 in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL and explored underlying mechanisms. Our results showed that in the presence of ox-LDL, XJP-1 significantly attenuated ox-LDL-mediated cytotoxicity, apoptosis, caspase-3 activation, reactive oxygen species (ROS) generation, and NADPH oxidase subunit (p22phox and p47phox) expression in HUVECs. In addition, the anticytotoxic and anti-apoptotic effect of XJP-1 was partially inhibited by a PI3K inhibitor (LY294002), an Akt inhibitor (SH-6), a specific eNOS inhibitor (l-NAME) and a NADPH oxidase inhibitor (DPI). In exploring the underlying mechanisms of XJP-1 action, we found that XJP-1 eliminated ox-LDL-induced dephosphorylation of Akt and eNOS in a dose-dependent manner. However, XJP-1 alone upregulation of Akt and eNOS phosphorylation were blocked by LY294002 and SH-6. Moreover, XJP-1 increased NO production, but this effect was abolished by LY294002, SH-6 and l-NAME. The inhibition of ox-LDL-induced endothelial dysfunction by XJP-1 is due at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.

  13. Oxidized low-density lipoprotein-induced periodontal inflammation is associated with the up-regulation of cyclooxygenase-2 and microsomal prostaglandin synthase 1 in human gingival epithelial cells

    SciTech Connect

    Nagahama, Yu; Obama, Takashi; Usui, Michihiko; Kanazawa, Yukari; Iwamoto, Sanju; Suzuki, Kazushige; Miyazaki, Akira; Yamaguchi, Tomohiro; Yamamoto, Matsuo; Itabe, Hiroyuki

    2011-10-07

    Highlights: {yields} OxLDL-induced responses in human gingival epithelial cells were studied. {yields} OxLDL enhanced the production of IL-8, IL-1{beta} and PGE{sub 2} in Ca9-22 cells. {yields} An NF-{kappa}B inhibitor suppressed the expression of COX-2 and mPGES1 induced by oxLDL. {yields} Unlike the case in macrophages, oxLDL did not increase the CD36 level. -- Abstract: Periodontitis is characterized by chronic gingival tissue inflammation, and inflammatory mediators such as IL-8 and prostaglandin E{sub 2} (PGE{sub 2}) are associated with disease progression. Previously we showed that oxidatively modified low-density lipoprotein (oxLDL) was present in gingival crevicular fluid. In this study, the role of oxLDL in the gingival epithelial cell inflammatory response was further investigated using Ca9-22 cells and primary human oral keratinocytes (HOK). Treatment of Ca9-22 cells and HOK with oxLDL induced an up-regulation of IL-8 and the PGE{sub 2}-producing enzymes, cyclooxygenase-2 and microsomal PGE{sub 2} synthase-1. These responses induced by oxLDL were significantly suppressed by a nuclear factor-kappa B (NF-{kappa}B) inhibitor. However, unlike the result in macrophages, oxLDL did not lead to an increase in CD36 expression in these two cells. These results suggest that oxLDL elicits gingival epithelial cell inflammatory responses through an activation of the NF-{kappa}B pathway. These data suggest a mechanistic link between periodontal disease and lipid metabolism-related disorders, including atherosclerosis.

  14. Icariin inhibits oxidized low-density lipoprotein-induced proliferation of vascular smooth muscle cells by suppressing activation of extracellular signal-regulated kinase 1/2 and expression of proliferating cell nuclear antigen.

    PubMed

    Hu, Yanwu; Liu, Kai; Yan, Mengtong; Zhang, Yang; Wang, Yadi; Ren, Liqun

    2016-03-01

    Icariin, a flavonoid isolated from the traditional Chinese herbal medicine Epimedium brevicornum Maxim, has been shown to possess anti-inflammatory, anti‑oxidant and anti-atherosclerotic activities in vivo and in vitro. The aim of the present study was to investigate the effects of icariin on oxidized low‑density lipoprotein (ox-LDL)-induced proliferation of vascular smooth muscle cells (VSMCs) and the possible underlying mechanism. VSMCs were cultured and pre‑treated with various concentrations of icariin (0, 10, 20 or 40 µm) prior to stimulation by ox‑LDL (50 µg/ml). Cell proliferation was evaluated by an MTT assay. Flow cytometry was used to study the influence of icariin on the cell cycle. Proliferating cell nuclear antigen (PCNA) expression and phosphorylation levels of extracellular signal-regulated kinase (ERK)1/2 were detected by western blot analysis. The results indicated that icariin significantly inhibited ox‑LDL‑induced proliferation of VSMCs and phosphorylation of ERK1/2. Furthermore, icariin also blocked the ox‑LDL‑induced cell‑cycle progression at G1/S‑interphase and downregulated the expression of PCNA in VSMCs. In conclusion, the present study indicated for the first time that icariin reduced the amount of ox‑LDL‑induced proliferation of VSMCs through suppression of PCNA expression and inactivation of ERK1/2.

  15. Minimally modified low-density lipoprotein induces macrophage endoplasmic reticulum stress via toll-like receptor 4.

    PubMed

    Yao, Shutong; Yang, Nana; Song, Guohua; Sang, Hui; Tian, Hua; Miao, Cheng; Zhang, Ying; Qin, Shucun

    2012-07-01

    Minimally modified low-density lipoprotein (mm-LDL) induces intimal foam cell formation, which is promoted by endoplasmic reticulum stress (ERS), a cross-point to link cellular processes with multiple risk factors that exist in all stages of atherosclerosis. However, it remains unclear whether mm-LDL-induced lipid accumulation in macrophages involves ERS and its underlying mechanisms. We showed that mm-LDL induced the accumulation of lipid droplets in RAW264.7 macrophages with increased free cholesterol in the endoplasmic reticulum, which was markedly attenuated by pretreatment with an antibody against toll-like receptor 4 (TLR4). Additionally, mm-LDL stimulated the transport of Cy3-labeled activating transcription factor 6 (ATF6), a key sensor to the unfolded protein response (UPR), from cytoplasm into nucleus. The expression of phosphorylated inositol-requiring enzyme 1 (p-IRE1), another sensor to the UPR, and its two downstream molecules, X box binding protein 1 and glucose-regulated protein 78 (GRP78), were significantly upregulated by mm-LDL. The alterations induced by mm-LDL were all significantly inhibited by antibodies against TLR4 or CD36. In addition, the upregulation of p-IRE1 and GRP78 and the nuclear translocation of ATF6 induced by mm-LDL were significantly attenuated by TLR4 siRNA. These results suggest that mm-LDL may induce free cholesterol accumulation in the endoplasmic reticulum and subsequently stimulate ERS and activate the UPR signaling pathway mediated by ATF6 and IRE1 in macrophages, a process that is potentially mediated by TLR4. PMID:22480542

  16. Platelet endothelial cell adhesion molecule-1 (PECAM-1) inhibits low density lipoprotein-induced signaling in platelets.

    PubMed

    Relou, Ingrid A M; Gorter, Gertie; Ferreira, Irlando Andrade; van Rijn, Herman J M; Akkerman, Jan-Willem N

    2003-08-29

    At physiological concentrations, low density lipoprotein (LDL) increases the sensitivity of platelets to aggregation- and secretion-inducing agents without acting as an independent activator of platelet functions. LDL sensitizes platelets by inducing a transient activation of p38MAPK, a Ser/Thr kinase that is activated by the simultaneous phosphorylation of Thr180 and Tyr182 and is an upstream regulator of cytosolic phospholipase A2 (cPLA2). A similar transient phosphorylation of p38MAPK is induced by a peptide mimicking amino acids 3359-3369 in apoB100 called the B-site. Here we report that the transient nature of p38MAPK activation is caused by platelet endothelial cell adhesion molecule 1 (PECAM-1), a receptor with an immunoreceptor tyrosine-based inhibitory motif. PECAM-1 activation by cross-linking induces tyrosine phosphorylation of PECAM-1 and a fall in phosphorylated p38MAPK and cPLA2. Interestingly, LDL and the B-site peptide also induce tyrosine phosphorylation of PECAM-1, and studies with immunoprecipitates indicate the involvement of c-Src. Inhibition of the Ser/Thr phosphatases PP1/PP2A (okadaic acid) makes the transient p38MAPK activation by LDL and the B-site peptide persistent. Inhibition of Tyr-phosphatases (vanadate) increases Tyr-phosphorylated PECAM-1 and blocks the activation of p38MAPK. Together, these findings suggest that, following a first phase in which LDL, through its B-site, phosphorylates and thereby activates p38MAPK, a second phase is initiated in which LDL activates PECAM-1 and induces dephosphorylation of p38MAPK via activation of the Ser/Thr phosphatases PP1/PP2A. PMID:12775720

  17. Protective Effect of Irisin on Atherosclerosis via Suppressing Oxidized Low Density Lipoprotein Induced Vascular Inflammation and Endothelial Dysfunction

    PubMed Central

    Zhang, Yuzhu; Mu, Qian; Zhou, Zheng; Song, Haibo; Zhang, Yuan; Wu, Fei; Jiang, Miao; Wang, Fang; Zhang, Wen; Li, Liang; Shao, Lei; Wang, Xingli; Li, Shiwu; Yang, Lijun; Wu, Qi; Zhang, Mingxiang; Tang, Dongqi

    2016-01-01

    Irisin, a newly discovered myokine, is considered as a promising candidate for the treatment of metabolic disturbances and cardiovascular diseases. In the present study, we used two animal models, apolipoprotein E-deficient mice fed on a high-cholesterol diet and a mouse carotid partial ligation model to test the anti-atherosclerotic effect of irisin. Irisin treatment (0.5 μg/g body weight/day) significantly reduced the severity of aortic atherosclerosis in apolipoprotein E-deficient mice fed on a high-cholesterol diet and suppressed carotid neointima formation in a carotid partial ligation model. It was associated with decreased inflammation and cell apoptosis in aortic tissues. In addition, in a cell culture model, irisin restored ox-LDL-induced human umbilical vein endothelial cell dysfunction by reducing the levels of inflammatory genes via inhibiting the reactive oxygen species (ROS)/ p38 MAPK/ NF-κB signaling pathway activation and inhibiting cell apoptosis via up-regulating Bcl-2 and down-regulating Bax and caspase-3 expression. Our study demonstrated that irisin significantly reduced atherosclerosis in apolipoprotein E-deficient mice via suppressing ox-LDL-induced cell inflammation and apoptosis, which might have a direct therapeutic effect on atherosclerotic diseases. PMID:27355581

  18. Tiliroside and gnaphaliin inhibit human low density lipoprotein oxidation.

    PubMed

    Schinella, Guillermo R; Tournier, Horacio A; Máñez, Salvador; de Buschiazzo, Perla M; Del Carmen Recio, María; Ríos, José Luis

    2007-01-01

    Two flavonoids, gnaphaliin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their capacity to inhibit Cu(2+)-induced human low density lipoprotein (LDL) and diluted plasma oxidation. LDL oxidation was monitored by conjugated diene, thiobarbituric acid-reactive substances (TBARS) formation and electrophoretic mobility on agarose gel. Gnaphaliin and tiliroside increased the lag-phase for diene conjugate production in a dose-dependent manner. The reduction of TBARS production confirmed the antioxidant activity of gnaphaliin and tiliroside with 50% inhibitory concentration (IC(50)) values of 8.0+/-3.9 microM and 7.0+/-2.6 microM respectively. Furthermore, the flavonoids negated the Cu(2+)-induced increase in electrophoretic mobility of LDL. Antioxidant activity of gnaphaliin and tiliroside was significantly different when diluted plasma was oxidised by adding 1 mM CuSO(4). Although both flavonoids again reduced the TBARS production, tiliroside showed higher activity than gnaphaliin (IC(50)=10.6+/-2.5 microM vs. IC(50)>50 microM). In conclusion, tiliroside and gnaphaliin are antioxidants against in vitro Cu(2+)-induced LDL oxidation in the same order of magnitude compared to that of the reference drug, probucol.

  19. Oxidized low-density lipoprotein alters endothelial progenitor cell populations.

    PubMed

    Cui, Yuqi; Narasimhulu, Chandrakala A; Liu, Lingjuan; Li, Xin; Xiao, Yuan; Zhang, Jia; Xie, Xiaoyun; Hao, Hong; Liu, Jason Z; He, Guanglong; Cowan, Peter J; Cui, Lianqun; Zhu, Hua; Parthasarathy, Sampath; Liu, Zhenguo

    2015-06-01

    Oxidized low-density lipoprotein (ox-LDL) is critical to atherosclerosis in hyperlipidemia. Bone marrow (BM)-derived endothelial progenitor cells (EPCs) are important to preventing atherosclerosis, and significantly decreased in hyperlipidemia. This study was to demonstrate ox-LDL and hyperlipidemia could exhibit similar effect on EPC population and the role of reactive oxygen species (ROS). ROS production in BM and blood was significantly increased in male C57BL/6 mice with intravenous ox-LDL treatment, and in hyperlipidemic LDL receptor knockout mice with 4-month high-fat diet. ROS formation was effectively blocked with overexpression of antioxidant enzymes or N-acetylcysteine treatment. In hyperlipidemic and ox-LDL-treated mice, c-Kit(+)/CD31(+) cell number in BM and blood, and Sca-1(+)/Flk-1(+) cell number in blood, not in BM, were significantly decreased, which were not affected by inhibiting ROS production, while blood CD34(+)/Flk-1(+) cell number was significantly increased that was prevented with reduced ROS formation. However, blood CD34(+)/CD133(+) cell number increased in ox-LDL-treated mice, while decreased in hyperlipidemic mice. These data suggested that ox-LDL produced significant changes in BM and blood EPC populations similar (but not identical) to chronic hyperlipidemia with predominantly ROS-independent mechanism(s).

  20. Oxidized low-density lipoprotein (Oxidized LDL) and the risk of preeclampsia.

    PubMed

    Qiu, C; Phung, T T T; Vadachkoria, S; Muy-Rivera, M; Sanchez, S E; Williams, M A

    2006-01-01

    Oxidative stress plays an important role in the pathophysiology of preeclampsia. In a case-control study of 99 women with preeclampsia and 99 controls, we assessed maternal plasma oxidized low-density lipoprotein (oxidized LDL) in relation to preeclampsia risk. Logistic regression procedures were used to derive odds ratios (OR) and 95 % confidence intervals (CI). Plasma oxidized LDL was determined using enzyme immunoassay. Maternal plasma oxidized LDL was significantly positively correlated with lipids in both cases and controls. After adjusting for nulliparity, pre-pregnancy body mass index, physical inactivity, family history of chronic hypertension and plasma vitamin C concentrations, women who had elevated oxidized LDL concentrations ( > or = 50 U/l) experienced a 2.9-fold increased risk of preeclampsia when compared with women having lower oxidized LDL concentrations (95 % CI 1.4-5.9). The risk of preeclampsia was markedly increased in women who had both elevated oxidized LDL and elevated triglyceride concentrations (OR=8.9, 95 % CI 3.1-26.2). Women with both elevated oxidized LDL and low vitamin C concentrations experienced a 9.8-fold increased risk of preeclampsia (95 % CI 3.0-32.2). Our results confirm the role of oxidative stress in the pathogenesis of preeclampsia. Prospective studies are needed to determine if elevated oxidized LDL concentrations can predict the occurrence of preeclampsia.

  1. Inhibition of human low-density lipoprotein oxidation in vitro by ginger extracts.

    PubMed

    Gunathilake, K D Prasanna P; Rupasinghe, H P Vasantha

    2014-04-01

    Oxidative modification of low-density lipoprotein (LDL) is thought to play a key role in atherosclerotic plaque formation. Currently, there is a renewed interest in ginger because of its antioxidants and cardioprotective properties. The effects of ethanol, methanol, ethyl acetate, and hexane solvent extracts of ginger and pure major ginger constituents on Cu(2+)-induced oxidation of human LDL in vitro were examined. The LDL oxidation inhibition by ethanol, methanol, ethyl acetate, and hexane extracts of ginger was 71%, 76%, 67%, and 67%, respectively, at their optimum extraction conditions. Inhibition of LDL oxidation by water extracts of ginger, which was prepared by ultrasonic-assisted extraction conditions of 52°C for 15 min, was about 43%. Phenolic bioactives of ginger-6-gingerols, 8-gingerols, 10-gingerols, and 6-shogaol-seem to be strong inhibitors of Cu(+2)-induced LDL oxidation. Overall, ginger extracts, including the water extract possess the antioxidant activities to inhibit human LDL oxidation in vitro.

  2. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage

    SciTech Connect

    Frei, B. )

    1991-12-01

    The authors exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

  3. Betanin inhibits the myeloperoxidase/nitrite-induced oxidation of human low-density lipoproteins.

    PubMed

    Allegra, Mario; Tesoriere, Luisa; Livrea, Maria A

    2007-03-01

    Production of nitrogen dioxide by the activity of myeloperoxidase (MPO) in the presence of nitrite is now considered a key step in the pathophysiology of low-density lipoprotein (LDL) oxidation. This study shows that betanin, a phytochemical of the betalain class, inhibits the production of lipid hydroperoxides in human LDL submitted to a MPO/nitrite-induced oxidation. Kinetic measurements including time-course of particle oxidation and betanin consumption, either in the presence or in the absence of nitrite, suggest that the antioxidant effect is possibly the result of various actions. Betanin scavenges the initiator radical nitrogen dioxide and can also act as a lipoperoxyl radical-scavenger. In addition, unidentified oxidation product(s) of betanin by MPO/nitrite inhibit(s) the MPO/nitrite-induced LDL oxidation as effectively as the parent compound. In the light of betanin bioavailability and post-absorbtion distribution in humans, present findings may suggest favourable in vivo activity of this phytochemical.

  4. Particulate Matter Promotes In Vitro Receptor-Recognizable Low-Density Lipoprotein Oxidation and Dysfunction of Lipid Receptors

    PubMed Central

    Manzano-León, Natalia; Mas-Oliva, Jaime; Sevilla-Tapia, Laura; Morales-Bárcenas, Rocío; Serrano, Jesús; O’Neill, Marie S.; García-Cuellar, Claudia M.; Quintana, Raúl; Vázquez-López, Inés

    2015-01-01

    Particulate matter may promote cardiovascular disease, possibly as a consequence of its oxidative potential. Studies using susceptible animals indicate that particulate matter aggravates atherosclerosis by increasing lipid/macrophage content in plaques. Macrophage lipid uptake requires oxidized low-density lipoprotein and scavenger receptors; same receptors are involved in particulate matter uptake. We studied in vitro particulate matter potential to oxidize low-density lipoproteins and subsequent cell uptake through scavenger receptors. Particulate matter-induced low-density lipoproteins oxidation was evaluated by the thiobarbituric acid assay. Binding/internalization was tested in wild type and scavenger receptor–transfected Chinese hamster ovary cells, and in RAW264.7 cells using fluorescently labeled low-density lipoproteins. Dose-dependent binding/internalization only occurred in scavenger receptor–transfected Chinese hamster ovary cells and RAW264.7 cells. Competition binding/internalization using particles showed that particulate matter induced decreased binding (~50%) and internalization (~70%) of particle-oxidized low-density lipoproteins and native low-density lipoproteins. Results indicate that particulate matter was capable of oxidizing low-density lipoproteins, favoring macrophage internalization, and also altered scavenger and low-density lipoproteins receptor function. PMID:23297186

  5. Stimulated arachidonate metabolism during foam cell transformation of mouse peritoneal macrophages with oxidized low density lipoprotein.

    PubMed Central

    Yokode, M; Kita, T; Kikawa, Y; Ogorochi, T; Narumiya, S; Kawai, C

    1988-01-01

    Changes in arachidonate metabolism were examined in mouse peritoneal macrophages incubated with various types of lipoproteins. Oxidized low density lipoprotein (LDL) was incorporated by macrophages and stimulated macrophage prostaglandin E2 (PGE2) and leukotriene C4 syntheses, respectively, 10.8- and 10.7-fold higher than by the control. Production of 6-keto-PGF1 alpha, a stable metabolite of prostacyclin, was also stimulated. No stimulation was found with native LDL, which was minimally incorporated by the cells. Acetylated LDL and beta-migrating very low density lipoprotein (beta-VLDL), though incorporated more efficiently than oxidized LDL, also had no stimulatory effect. When oxidized LDL was separated into the lipoprotein-lipid peroxide complex and free lipid peroxides, most of the stimulatory activity was found in the former fraction, indicating that stimulation of arachidonate metabolism in the cell is associated with uptake of the lipoprotein-lipid peroxide complex. These results suggest that peroxidative modification of LDL could contribute to the progression of atheroma by stimulating arachidonate metabolism during incorporation into macrophages. Images PMID:3125226

  6. Oxidized low density lipoprotein increases acetylcholinesterase activity correlating with reactive oxygen species production.

    PubMed

    Yamchuen, Panit; Aimjongjun, Sathid; Limpeanchob, Nanteetip

    2014-12-01

    Hyperlipidemia, low density lipoproteins (LDL) and their oxidized forms, and oxidative stress are suspected to be a key combination in the onset of AD and acetylcholinesterase (AChE) plays a part in this pathology. The present study aimed to link these parameters using differentiated SH-SY5Y human neuroblastoma cells in culture. Both mildly and fully oxidized human LDL (mox- and fox-LDL), but not native (non-oxidized) LDL were cytotoxic in dose- and time-dependent patterns and this was accompanied by an increased production of intracellular reactive oxygen species (ROS). Oxidized LDL (10-200 μg/mL) augmented AChE activity after 4 and 24h treatments, respectively while the native LDL was without effect. The increased AChE with oxidized LDLs was accompanied by a proportionate increase in intracellular ROS formation (R=0.904). These findings support the notion that oxidized LDLs are cytotoxic and that their action on AChE may reduce central cholinergic transmission in AD and affirm AChE as a continued rational for anticholinesterase therapy but in conjunction with antioxidant/antihyperlipidemic cotreatments.

  7. Sweet potato (Ipomoea batatas L.) leaves suppressed oxidation of low density lipoprotein (LDL) in vitro and in human subjects.

    PubMed

    Nagai, Miu; Tani, Mariko; Kishimoto, Yoshimi; Iizuka, Maki; Saita, Emi; Toyozaki, Miku; Kamiya, Tomoyasu; Ikeguchi, Motoya; Kondo, Kazuo

    2011-05-01

    Sweet potato (Ipomoea batatas L.) leaves are consumed as vegetables around the world, especially in Southeast Asia. The aim of this study was to investigate the inhibitory effect of sweet potato leaves on low-density lipoprotein oxidation in vitro and in human subjects. We compared the antioxidant activity of 8 kinds of sweet potato leaves. Every sweet potato leaf had high radical scavenging activity and prolonged a lag time for starting low-density lipoprotein oxidation in vitro. We found that sweet potato leaves contained abundant polyphenol compounds and the radical scavenging activity and prolongation rate of lag time were highly correlated with total polyphenol content. We also confirmed that thiobarbituric acid reactive substances production was increased in endothelial cell-mediated low-density lipoprotein oxidation, which was decreased by treatment with sweet potato leaves. We further measured the low-density lipoprotein oxidizability in 13 healthy volunteers after their intake of 18 g of "Suioh", raw sweet potato leaves. "Suioh" prolonged a lag time for starting low-density lipoprotein oxidation and decreased low-density lipoprotein mobility. These results suggest that sweet potato leaves have antioxidant activity leading to the suppression of low-density lipoprotein oxidation.

  8. Lectin-like oxidized low-density lipoprotein receptor (LOX-1) in sickle cell disease vasculopathy.

    PubMed

    Chen, Mingyi; Qiu, Hong; Lin, Xin; Nam, David; Ogbu-Nwobodo, Lucy; Archibald, Hannah; Joslin, Amelia; Wun, Ted; Sawamura, Tatsuya; Green, Ralph

    2016-09-01

    Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is an endothelial receptor for oxidized LDL. Increased expression of LOX-1 has been demonstrated in atherosclerotic lesions and diabetic vasculopathy. In this study, we investigate the expression of LOX-1 receptor in sickle cell disease (SCD) vasculopathy. Expression of LOX-1 in brain vascular endothelium is markedly increased and LOX-1 gene expression is upregulated in cultured human brain microvascular endothelial cells by incubation with SCD erythrocytes. Also, the level of circulating soluble LOX-1 concentration is elevated in the plasma of SCD patients. Increased LOX-1 expression in endothelial cells is potentially involved in the pathogenesis of SCD vasculopathy. Soluble LOX-1 concentration in SCD may provide a novel biomarker for risk stratification of sickle cell vascular complications. PMID:27519944

  9. Oxidized low-density lipoprotein (Ox-LDL) impacts on erythrocyte viscoelasticity and its molecular mechanism.

    PubMed

    Wang, Xiang; Yang, Li; Liu, Yao; Gao, Wei; Peng, Weiyan; Sung, K-L Paul; Sung, Lanping Amy

    2009-10-16

    The oxidized low-density lipoprotein (Ox-LDL) plays an important role in atherosclerosis, yet it remains unclear if it damages circulating erythrocytes. In this study, erythrocyte deformability and its membrane proteins after Ox-LDL incubations are investigated by micropipette aspiration, thiol radical measurement, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Results show that Ox-LDL incubation reduces the erythrocyte deformability, decreases free thiol radical contents in erythrocytes, and induces the cross-linking among membrane proteins. SDS-PAGE analysis reveals a high molecular weight (HMW) complex as well as new bands between spectrins and band 3 and reduced ratios between band 3 and other major membrane skeletal proteins. Analyses indicate that Ox-LDL makes erythrocytes harder to deform through a molecular mechanism by which the oxidation of free thiol radicals forms disulfide bonds among membrane skeletal proteins.

  10. The effects of ascorbate and dehydroascorbate on the oxidation of low-density lipoprotein.

    PubMed Central

    Stait, S E; Leake, D S

    1996-01-01

    Ascorbate at concentrations of 60-100 microM inhibits the modification of freshly prepared low-density lipoprotein (LDL) by macrophages. With 'moderately oxidized' LDL (produced by prolonged storage in a refrigerator), however, ascorbate does not inhibit LDL modification by macrophages and actually modifies the LDL itself in the absence of macrophages [Stait and Leake (1994) FEBS Lett. 341, 263-267]. We have now shown that dehydroascorbate can modify both 'fresh' LDL and moderately oxidized LDL in a dose-dependent manner to increase its uptake by macrophages. The modification of moderately oxidized LDL by ascorbate and dehydroascorbate or of 'fresh' LDL by dehydroascorbate is dependent on the presence of iron or copper. In 'fresh' LDL, ascorbate inhibited conjugated-diene formation by copper. In moderately oxidized LDL, the number of conjugated dienes present was decreased rapidly in the presence of copper and ascorbate. Dehydroascorbate decreased the lag phase and increased the rate of copper-induced conjugated-diene formation in 'fresh' LDL (although in some experiments it inhibited the formation of conjugated dienes). The ascorbate-modified moderately oxidized LDL was taken up by macrophages by their scavenger receptors, as the uptake was inhibited by polyinosinic acid or fucoidan. Ascorbate and dehydroascorbate therefore have the potential to increase LDL oxidation under certain conditions, but whether or not they do so in vivo is unknown. PMID:8973543

  11. Antioxidant effects of 14 Chinese traditional medicinal herbs against human low-density lipoprotein oxidation

    PubMed Central

    Lin, Hsin-Hung; Charles, Albert Linton; Hsieh, Chang-Wei; Lee, Ya-Chi; Ciou, Jhih-Ying

    2014-01-01

    The relationship between the antioxidant activities and inhibitory effect of 14 Chinese medicinal herbs against oxidized low-density lipoprotein (LDL) formation was evaluated. Prolongation of the lag phase of LDL oxidation depended on the concentration of the herbs. The concentration of each herb that was able to prolong the lag time by about two-fold was calculated and expressed as doubling-time concentration. The lower the doubling-time concentration, the stronger the inhibitory effect exhibited toward LDL oxidation. Among them, Chrysanthemi Flos (Chrysanthemum morifolium ramat; 甘菊花 gān jú huā), Crataegi Fructus (Crataegus pinnatifida Bge. var. major N.E.Br.; 山楂 shān zhā), and Roselle (Hibiscus sabdariffa Linn.; 洛神 luò shén) showed significant inhibitory effects. Correlation coefficients between doubling-time concentration and radical-scavenging activities were high; the total phenolic content was also high. In conclusion, phenolic compounds contributed not only to antioxidant activities, but also to the inhibitory effect against LDL oxidation. Chrysanthemi Flos, Crataegi Fructus, and H. sabdariffa, with lower doubling-time concentrations, could be potent phytochemical agents to reduce LDL oxidation and prevent the progression of atherosclerosis. PMID:26151009

  12. Switching to black rice diets modulates low-density lipoprotein oxidation and lipid measurements in rabbits.

    PubMed

    Abdel-Moemin, Aly R

    2011-04-01

    The effect of white and black rice consumption on lipid profile, hydroperoxides, thiobarbituric reactive substances and oxidized low-density lipoprotein (LDL) induced by hypercholesterolemia was investigated in 24 male rabbits; a purified normal diet (NC, n = 6), a high fat/cholesterol (1.0 g/100 g) diet (PC group, n = 6), a high fat/cholesterol diet with 25 g/100 g white ground rice (PCWR group, n = 6), 25 g/100 g black ground rice (PCBR group, n = 6) for 10 weeks. Blood samples were collected for lipid measurements. Results indicate that serum high-density lipoprotein-cholesterol was higher (P < 0.05) in the PCBR compared with the PC and PCWR groups. Hydroperoxides and thiobarbituric reactive substances were significantly lower (P < 0.05) in the PCBR compared with PCWR and PC groups. Cyanidin-3-glucoside (Cy-3-Glu) and peonidin-3-glucoside have been tested in vitro against copper-mediated low-density lipoprotein. Cy-3-Glu was excelled peonidin-3-glucoside by increasing the lag time of NC from 80 to 500 minutes in the presence of 2.0 μM of Cy-3-Glu. Hierarchically, black rice rabbits group was given the best results compared with other groups. The results may be indicating to a suggested mechanism (anthocyanins protection; Cy-3-Glu) of the cardioprotective effect of black rice. PMID:21289511

  13. Pistachio intake increases high density lipoprotein levels and inhibits low-density lipoprotein oxidation in rats.

    PubMed

    Aksoy, Nur; Aksoy, Mehmet; Bagci, Cahit; Gergerlioglu, H Serdar; Celik, Hakim; Herken, Emine; Yaman, Abdullah; Tarakcioglu, Mehmet; Soydinc, Serdar; Sari, Ibrahim; Davutoglu, Vedat

    2007-05-01

    There is increasing evidence that nuts have protective effects against coronary artery disease by improving lipid profile and inhibiting lipid oxidation. However, data about pistachio nuts are limited, and to our knowledge, there is no study investigating the effects of pistachio intake on lipid oxidation and serum antioxidant levels. This study, therefore, sought to determine the effects of pistachio intake on serum lipids and determine whether consumption of pistachio would alter serum antioxidant levels. Rats were randomly divided into three groups (n=12 for each): control group fed basic diet for 10 weeks and treated groups fed basic diet plus pistachio which constituted 20% and 40% of daily caloric intake, respectively. Consumption of pistachio as 20% of daily caloric intake increased high-density lipoprotein (HDL) levels and decreased total cholesterol (TC)/HDL ratio, compared with those not taking pistachio. However, TC, low-density lipoprotein (LDL) cholesterol and triglyceride levels were unaffected by pistachio consumption. Consumption of pistachio as 20% of daily caloric intake increased serum paraoxonase activity by 35% and arylesterase activity by 60%, which are known to inhibit LDL cholesterol oxidation, compared with the control group. However, increased antioxidant activity was blunted when pistachio intake was increased to 40% of daily caloric intake. In conclusion, the present results show that consumption of pistachio as 20% of daily caloric intake leads to significant improvement in HDL and TC/HDL ratio and inhibits LDL cholesterol oxidation. These results suggest that pistachio may be beneficial for both prevention and treatment of coronary artery disease.

  14. Terminalia bellirica Extract Inhibits Low-Density Lipoprotein Oxidation and Macrophage Inflammatory Response in Vitro.

    PubMed

    Tanaka, Miori; Kishimoto, Yoshimi; Saita, Emi; Suzuki-Sugihara, Norie; Kamiya, Tomoyasu; Taguchi, Chie; Iida, Kaoruko; Kondo, Kazuo

    2016-01-01

    The deciduous tree Terminalia bellirica found in Southeast Asia is extensively used in traditional Indian Ayurvedic medicine for the treatment of hypertension, rheumatism, and diabetes. The anti-atherogenic effect of Terminalia bellirica fruit has not been fully elucidated. Here, we investigated the effect of Terminalia bellirica extract (TBE) on low-density lipoprotein (LDL) oxidation and inflammation in macrophages. TBE showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (EC50: 7.2 ± 1.2 μg/mL) and 15-lipoxygenase inhibitory activity. TBE also significantly inhibited free radical-induced LDL oxidation compared to the solvent control in vitro. In THP-1 macrophages, TBE treatment resulted in significant decreases of the mRNA expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and lectin-like oxidized LDL receptor-1 (LOX-1). TBE also reduced matrix metalloproteinase (MMP)-9 secretion and intracellular reactive oxygen species (ROS) production in THP-1 macrophages. These results show that TBE has the inhibitory effects on LDL oxidation and macrophage inflammatory response in vitro, suggesting that its in vivo use might inhibit atherosclerosis plaque progression. PMID:27314393

  15. Terminalia bellirica Extract Inhibits Low-Density Lipoprotein Oxidation and Macrophage Inflammatory Response in Vitro

    PubMed Central

    Tanaka, Miori; Kishimoto, Yoshimi; Saita, Emi; Suzuki-Sugihara, Norie; Kamiya, Tomoyasu; Taguchi, Chie; Iida, Kaoruko; Kondo, Kazuo

    2016-01-01

    The deciduous tree Terminalia bellirica found in Southeast Asia is extensively used in traditional Indian Ayurvedic medicine for the treatment of hypertension, rheumatism, and diabetes. The anti-atherogenic effect of Terminalia bellirica fruit has not been fully elucidated. Here, we investigated the effect of Terminalia bellirica extract (TBE) on low-density lipoprotein (LDL) oxidation and inflammation in macrophages. TBE showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (EC50: 7.2 ± 1.2 μg/mL) and 15-lipoxygenase inhibitory activity. TBE also significantly inhibited free radical-induced LDL oxidation compared to the solvent control in vitro. In THP-1 macrophages, TBE treatment resulted in significant decreases of the mRNA expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and lectin-like oxidized LDL receptor-1 (LOX-1). TBE also reduced matrix metalloproteinase (MMP)-9 secretion and intracellular reactive oxygen species (ROS) production in THP-1 macrophages. These results show that TBE has the inhibitory effects on LDL oxidation and macrophage inflammatory response in vitro, suggesting that its in vivo use might inhibit atherosclerosis plaque progression. PMID:27314393

  16. Edaravone attenuates monocyte adhesion to endothelial cells induced by oxidized low-density lipoprotein.

    PubMed

    Li, Zhijuan; Cheng, Jianxin; Wang, Liping

    2015-10-30

    Oxidized low-density lipoprotein (oxLDL) plays a vital role in recruitment of monocytes to endothelial cells, which is important during early stages of atherosclerosis development. Edaravone, a potent and novel scavenger of free radicals inhibiting hydroxyl radicals, has been clinically used to reduce the neuronal damage following ischemic stroke. In the present study, Edaravone was revealed to markedly reduce oxLDL-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). The inhibitory mechanism of Edaravone was associated with suppression of the chemokine MCP-1 and adhesion molecule VCAM-1 and ICAM-1 expression. In addition, luciferase reporter assay results revealed that administration of Edaravone attenuated the increase in NF-κB transcriptional activity induced by oxLDL. Notably, it's also shown that Edaravone treatment blocked oxLDL induced p65 nuclear translocation in HUVECs. Results indicate that Edaravone negatively regulates endothelial inflammation.

  17. Overexpression of LOXIN Protects Endothelial Progenitor Cells From Apoptosis Induced by Oxidized Low Density Lipoprotein.

    PubMed

    Veas, Carlos; Jara, Casandra; Willis, Naomi D; Pérez-Contreras, Karen; Gutierrez, Nicolas; Toledo, Jorge; Fernandez, Paulina; Radojkovic, Claudia; Zuñiga, Felipe A; Escudero, Carlos; Aguayo, Claudio

    2016-04-01

    Human endothelial progenitor cells (hEPC) are adult stem cells located in the bone marrow and peripheral blood. Studies have indicated that hEPC play an important role in the recovery and repair of injured endothelium, however, their quantity and functional capacity is reduced in several diseases including hypercholesterolemia. Recently, it has been demonstrated that hEPC express lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its activation by oxidized low-density lipoprotein (ox-LDL) induces cellular dysfunction and apoptosis. This study aimed to investigate whether overexpression of LOXIN, a truncated isoform of LOX-1 that acts as a dominant negative, plays a protective role against ox-LDL-induced apoptosis in hEPC. Human endothelial progenitor cells exposed to ox-LDL showed a significant increase in LOX-1 expression, and apoptosis began at ox-LDL concentrations above 50 μg/mL. All hEPC apoptosed at 200 μg/mL ox-LDL. High LOXIN expression was generated using adenoviral systems in hEPC and SiHa cells transduced with 100 colony-forming units per cell. Transduced LOXIN localized to the plasma membrane and blocked ox-LDL uptake mediated by LOX-1. Overexpression of LOXIN protected hEPC from ox-LDL-induced apoptosis, and therefore maybe a novel way of improving hEPC function and quantity. These results suggest that adenoviral vectors of LOXIN may provide a possible treatment for diseases related to ox-LDL and vascular endothelium dysfunction, including atherosclerosis.

  18. Overexpression of LOXIN Protects Endothelial Progenitor Cells From Apoptosis Induced by Oxidized Low Density Lipoprotein.

    PubMed

    Veas, Carlos; Jara, Casandra; Willis, Naomi D; Pérez-Contreras, Karen; Gutierrez, Nicolas; Toledo, Jorge; Fernandez, Paulina; Radojkovic, Claudia; Zuñiga, Felipe A; Escudero, Carlos; Aguayo, Claudio

    2016-04-01

    Human endothelial progenitor cells (hEPC) are adult stem cells located in the bone marrow and peripheral blood. Studies have indicated that hEPC play an important role in the recovery and repair of injured endothelium, however, their quantity and functional capacity is reduced in several diseases including hypercholesterolemia. Recently, it has been demonstrated that hEPC express lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its activation by oxidized low-density lipoprotein (ox-LDL) induces cellular dysfunction and apoptosis. This study aimed to investigate whether overexpression of LOXIN, a truncated isoform of LOX-1 that acts as a dominant negative, plays a protective role against ox-LDL-induced apoptosis in hEPC. Human endothelial progenitor cells exposed to ox-LDL showed a significant increase in LOX-1 expression, and apoptosis began at ox-LDL concentrations above 50 μg/mL. All hEPC apoptosed at 200 μg/mL ox-LDL. High LOXIN expression was generated using adenoviral systems in hEPC and SiHa cells transduced with 100 colony-forming units per cell. Transduced LOXIN localized to the plasma membrane and blocked ox-LDL uptake mediated by LOX-1. Overexpression of LOXIN protected hEPC from ox-LDL-induced apoptosis, and therefore maybe a novel way of improving hEPC function and quantity. These results suggest that adenoviral vectors of LOXIN may provide a possible treatment for diseases related to ox-LDL and vascular endothelium dysfunction, including atherosclerosis. PMID:26771151

  19. Cholesteryl Ester Hydroperoxides Are Biologically Active Components of Minimally Oxidized Low Density Lipoprotein*S⃞

    PubMed Central

    Harkewicz, Richard; Hartvigsen, Karsten; Almazan, Felicidad; Dennis, Edward A.; Witztum, Joseph L.; Miller, Yury I.

    2008-01-01

    Oxidation of low density lipoprotein (LDL) occurs in vivo and significantly contributes to the development of atherosclerosis. An important mechanism of LDL oxidation in vivo is its modification with 12/15-lipoxygenase (LO). We have developed a model of minimally oxidized LDL (mmLDL) in which native LDL is modified by cells expressing 12/15LO. This mmLDL activates macrophages inducing membrane ruffling and cell spreading, activation of ERK1/2 and Akt signaling, and secretion of proinflammatory cytokines. In this study, we found that many of the biological activities of mmLDL were associated with cholesteryl ester (CE) hydroperoxides and were diminished by ebselen, a reducing agent. Liquid chromatography coupled with mass spectroscopy demonstrated the presence of many mono- and polyoxygenated CE species in mmLDL but not in native LDL. Nonpolar lipid extracts of mmLDL activated macrophages, although to a lesser degree than intact mmLDL. The macrophage responses were also induced by LDL directly modified with immobilized 12/15LO, and the nonpolar lipids extracted from 12/15LO-modified LDL contained a similar set of oxidized CE. Cholesteryl arachidonate modified with 12/15LO also activated macrophages and contained a similar collection of oxidized CE molecules. Remarkably, many of these oxidized CE were found in the extracts of atherosclerotic lesions isolated from hyperlipidemic apoE–/– mice. These results suggest that CE hydroperoxides constitute a class of biologically active components of mmLDL that may be relevant to proinflammatory activation of macrophages in atherosclerotic lesions. PMID:18263582

  20. Effect of ethyl esterification of phenolic acids on low-density lipoprotein oxidation.

    PubMed

    Chalas, J; Claise, C; Edeas, M; Messaoudi, C; Vergnes, L; Abella, A; Lindenbaum, A

    2001-02-01

    Inhibition of copper-induced low-density lipoprotein (LDL) oxidation by phenolic acids and their ethyl esters was investigated. LDL oxidation was evaluated by the hydroperoxide concentration and the chromatographic pattern of apoprotein fractions after fast protein liquid chromatography (FPLC). Antiradical properties against 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical and 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) were also investigated, and lipophilicity determined by thin-layer chromatography. Caffeic acid at 5 microM and sinapic acid at 10 microM protected LDL against oxidation, inhibiting both hydroperoxide formation and the increase of apoprotein negative charge. Ferulic, gallic and p-hydroxy cinnamic acids were ineffective. Ethyl esterification increased the lipophilicity of the five acids, and enhanced the antioxidant properties of caffeic, sinapic and ferulic acids. Ethyl caffeate was protective at 1 microM. In contrast, gallic and p-hydroxy cinnamic ethyl esters were ineffective. Our results indicate that ethyl esterification of phenolic acids increases lipophilicity of their ethyl esters and may enable a better incorporation into the lipid layer of the LDL particle and the exertion of their antioxidant effect in the true site of lipoperoxidation. However, increasing lipophilicity is not the only mechanism able to potentiate preexisting antioxidant properties of molecules, and probably other mechanisms are implicated.

  1. Antioxidant activities of black and yellow soybeans against low density lipoprotein oxidation.

    PubMed

    Takahashi, Rie; Ohmori, Reiko; Kiyose, Chikako; Momiyama, Yukihiko; Ohsuzu, Fumitaka; Kondo, Kazuo

    2005-06-01

    Several studies have demonstrated that the daily intakes of soy foods were associated with a reduced cardiovascular risk. The aim of our study was to investigate the inhibitory effect of black soybeans on low density lipoprotein (LDL) oxidation in comparison to yellow soybeans. The extract from black soybean had a longer LDL oxidation lag time than that from yellow soybean (205 +/- 16 and 65 +/- 3 min, respectively). When both soybeans were divided into the seed coat and the mixture of the germ and cotyledon, the diluted extract solution from the black soybean seed coat prolonged the lag time significantly more than the original extract of the yellow soybean seed coat. On the other hand, antioxidant effects of the extract from the mixture of germs and cotyledons were similar in both soybeans. Regarding total polyphenol contents, the seed coat of black soybean had a higher polyphenol content than that of yellow soybean (29.0 +/- 0.56 and 0.45 +/- 0.02 mg/g, respectively). Interestingly, the mixture of the germ and cotyledon hydrolyzed by beta-glucosidase in both soybeans showed a stronger inhibitory effect on LDL oxidation than that before being hydrolyzed by beta-glucosidase. These results suggest that black soybeans may be more effective in inhibiting LDL oxidation than yellow soybeans because of total polyphenols contents in its seed coat. In addition, aglycones, which are rich in soybeans fermented or hydrolyzed by beta-glucosidase, may play a crucial role in the prevention of oxidation-related diseases. PMID:15913328

  2. Production of oxidized lipids during modification of low-density lipoprotein by macrophages or copper.

    PubMed Central

    Carpenter, K L; Wilkins, G M; Fussell, B; Ballantine, J A; Taylor, S E; Mitchinson, M J; Leake, D S

    1994-01-01

    The oxidation of low-density lipoprotein (LDL) is implicated in atherosclerosis. Lipids and oxidized lipids were analysed by gas chromatography and gas chromatography-mass spectrometry in human LDL incubated with mouse peritoneal macrophages (MPM) or copper (II) sulphate in Ham's F-10 medium or medium alone (control). MPM-modification and copper-catalysed oxidation of LDL resulted in the formation of oxysterols, mainly cholest-5-en-3 beta,7 beta-diol (7 beta-OH-CHOL); 7%-19% of the initial cholesterol was converted to 7 beta-OH-CHOL in 24 h. 7 beta-OH-CHOL levels in control LDL were very low. The increase in 7 beta-OH-CHOL in MPM and copper-oxidized LDL was accompanied by decreases in linoleate and arachidonate and increases in the electrophoretic mobility and degradation of LDL protein by 'target' macrophages. The concerted occurrence of these processes and their similarity in both MPM-modification and copper-catalysed oxidation of LDL were suggested by the highly significant cross-correlations. The fall in polyunsaturated fatty acid (PUFA) was accompanied by a directly proportional increase in electrophoretic mobility of the LDL. Production of 7 beta-OH-CHOL and protein degradation by macrophages showed modest elevations during the initial steep fall in PUFA, and showed their greatest increases as the levels of PUFA slowly approached zero. The levels of 7 beta-OH-CHOL and the degradation of LDL by macrophages were directly proportional. The degradation of LDL by macrophages increased rapidly as the electrophoretic mobility of LDL was slowly approaching its maximum level. PMID:7999000

  3. Uptake and Accumulation of Oxidized Low-Density Lipoprotein during Mycobacterium tuberculosis Infection in Guinea Pigs

    PubMed Central

    Palanisamy, Gopinath S.; Kirk, Natalie M.; Ackart, David F.; Obregón-Henao, Andrés; Shanley, Crystal A.; Orme, Ian M.; Basaraba, Randall J.

    2012-01-01

    The typical host response to infection of humans and some animals by M. tuberculosis is the accumulation of reactive oxygen species generating inflammatory cells into discrete granulomas, which frequently develop central caseous necrosis. In previous studies we showed that infection of immunologically naïve guinea pigs with M. tuberculosis leads to localized and systemic oxidative stress that results in a significant depletion of serum total antioxidant capacity and the accumulation of malondialdehyde, a bi-product of lipid peroxidation. Here we show that in addition, the generation of excessive reactive oxygen species in vivo resulted in the accumulation of oxidized low density lipoproteins (OxLDL) in pulmonary and extrapulmonary granulomas, serum and lung macrophages collected by bronchoalveolar lavage. Macrophages from immunologically naïve guinea pigs infected with M. tuberculosis also had increased surface expression of the type 1 scavenger receptors CD36 and LOX1, which facilitate the uptake of oxidized host macromolecules including OxLDL. Vaccination of guinea pigs with Bacillus Calmette Guerin (BCG) prior to aerosol challenge reduced the bacterial burden as well as the intracellular accumulation of OxLDL and the expression of macrophage CD36 and LOX1. In vitro loading of guinea pig lung macrophages with OxLDL resulted in enhanced replication of bacilli compared to macrophages loaded with non-oxidized LDL. Overall, this study provides additional evidence of oxidative stress in M. tuberculosis infected guinea pigs and the potential role OxLDL laden macrophages have in supporting intracellular bacilli survival and persistence. PMID:22493658

  4. Spin-labeling study of the oxidative damage to low-density lipoprotein.

    PubMed

    Singh, R J; Feix, J B; Mchaourab, H S; Hogg, N; Kalyanaraman, B

    1995-06-20

    In this study, we have spin-labeled the lysine and cysteine residues of low-density lipoprotein (LDL) using N-4-(2,2,6,6-tetramethylpiperidinyl-1-oxyl-4-yl) maleimide (MAL-6) and succinimidyl-2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylate (SSL), respectively. The electron spin resonance (ESR) spectrum of SSL bound to LDL indicated that the nitroxide moiety was relatively mobile. In contrast, the ESR spectrum of MAL-6 bound to LDL showed that the nitroxide moiety was rotationally restricted. Using the continuous-wave power saturation technique in the presence of hydrophobic and hydrophilic paramagnetic relaxing agents, we have determined that (i) approximately 60-70% of lysine-bound SSL is exposed to the aqueous phase, (ii) approximately 30-40% of SSL-LDL is buried in a hydrophobic region, and (iii) MAL-6 bound to LDL is localized predominantly in the hydrophobic region. During Cu(2+)-initiated oxidation of spin-labeled LDL, nitroxide labels located in a hydrophobic environment were predominantly degraded. Nitroxide destruction was inhibited by butylated hydroxytoluene, indicating the role of lipid peroxidation in this process. ESR data also showed that Cu2+ binding to lysine is essential for LDL oxidation. The spin label methodology may be useful for the investigation of site-specific radical reactions in LDL.

  5. [New biochemical methods for evaluation of the oxidative-antioxidative potential of low-density lipoproteins].

    PubMed

    Ragino, Iu I; Voevoda, M I; Kashtanova, E V; Ivanova, M V; Nikitin, Iu P

    2005-04-01

    Today one of the leading theories in the concept of atherogenesis underlines the key role of oxidized low-density lipoproteins (LDL). This paper describes new original and easy-to-use biochemical methods for evaluating the oxidative-antioxidative potential (LDL resistance to oxidation in vitro and the LDL level of alpha-tocopherol and retinol), as well as the results of their development and testing in 2 groups (62 patients with coronary atherosclerosis and 95 healthy individuals). LDL were isolated from their sera via precipitation with heparin and MnCl2. The precipitated LDL were washed in 0.9% NaCl solution and dissolved in 1 M NaCl solution. For evaluation of the resistance of LDL to oxidation in vitro, the precipitated LDL were incubated at 37 degrees C with 50 microM of copper ions; before and 0.5 h, 1.0 h, and 2.0 h after LDL incubation, TBARS products were determined by the fluorimetric technique after Schun J. et al. (1978). For evaluation of the antioxidative potntial of LDL, the concentrations of alpha-tocopheral and retinol in the precipitated LDL were measured by using the fluorimetric technique described by Taylor S. L. et al. (1976). The new methods were found to be highly reproducible. There was a high positive correlation (r = +0.98 +/- 0.04, p < 0.001) between the oxidative resistance of the LDL isolated from sera by ultracentrifugation and that of the precipitated LDL. There was also a high positive correlation (r = +0.79 +/- 0.09, p < 0.01) between the alpha-tocopherol and retinol levels determined by the fluorimetric technique and the LDL levels measured by the authors' method. The new methods were clinically tested with success. The significantly elevated baseline level of lipid perioxidation products in the precipitated LDL, the low oxidative resistance of the precipitated LDL in vitro, and reduced concentrations of alpha-tocopherol and retinol in the precipitated LDL were recorded in the patients with coronary atherosclerosis as compared to

  6. CD36 binds oxidized low density lipoprotein (LDL) in a mechanism dependent upon fatty acid binding.

    PubMed

    Jay, Anthony G; Chen, Alexander N; Paz, Miguel A; Hung, Justin P; Hamilton, James A

    2015-02-20

    The association of unesterified fatty acid (FA) with the scavenger receptor CD36 has been actively researched, with focuses on FA and oxidized low density lipoprotein (oxLDL) uptake. CD36 has been shown to bind FA, but this interaction has been poorly characterized to date. To gain new insights into the physiological relevance of binding of FA to CD36, we characterized FA binding to the ectodomain of CD36 by the biophysical method surface plasmon resonance. Five structurally distinct FAs (saturated, monounsaturated (cis and trans), polyunsaturated, and oxidized) were pulsed across surface plasmon resonance channels, generating association and dissociation binding curves. Except for the oxidized FA HODE, all FAs bound to CD36, with rapid association and dissociation kinetics similar to HSA. Next, to elucidate the role that each FA might play in CD36-mediated oxLDL uptake, we used a fluorescent oxLDL (Dii-oxLDL) live cell assay with confocal microscopy imaging. CD36-mediated uptake in serum-free medium was very low but greatly increased when serum was present. The addition of exogenous FA in serum-free medium increased oxLDL binding and uptake to levels found with serum and affected CD36 plasma membrane distribution. Binding/uptake of oxLDL was dependent upon the FA dose, except for docosahexaenoic acid, which exhibited binding to CD36 but did not activate the uptake of oxLDL. HODE also did not affect oxLDL uptake. High affinity FA binding to CD36 and the effects of each FA on oxLDL uptake have important implications for protein conformation, binding of other ligands, functional properties of CD36, and high plasma FA levels in obesity and type 2 diabetes.

  7. l-Cystathionine Inhibits the Mitochondria-Mediated Macrophage Apoptosis Induced by Oxidized Low Density Lipoprotein

    PubMed Central

    Zhu, Mingzhu; Du, Junbao; Chen, Siyao; Liu, Angie Dong; Holmberg, Lukas; Chen, Yonghong; Zhang, Chunyu; Tang, Chaoshu; Jin, Hongfang

    2014-01-01

    This study was designed to investigate the regulatory role of l-cystathionine in human macrophage apoptosis induced by oxidized low density lipoprotein (ox-LDL) and its possible mechanisms. THP-1 cells were induced with phorbol 12-myristate 13-acetate (PMA) and differentiated into macrophages. Macrophages were incubated with ox-LDL after pretreatment with l-cystathionine. Superoxide anion, apoptosis, mitochondrial membrane potential, and mitochondrial permeability transition pore (MPTP) opening were examined. Caspase-9 activities and expression of cleaved caspase-3 were measured. The results showed that compared with control group, ox-LDL treatment significantly promoted superoxide anion generation, release of cytochrome c (cytc) from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and cell apoptosis, in addition to reduced mitochondrial membrane potential as well as increased MPTP opening. However, 0.3 and 1.0 mmol/L l-cystathionine significantly reduced superoxide anion generation, increased mitochondrial membrane potential, and markedly decreased MPTP opening in ox-LDL + l-cystathionine macrophages. Moreover, compared to ox-LDL treated-cells, release of cytc from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and apoptosis levels in l-cystathionine pretreated cells were profoundly attenuated. Taken together, our results suggested that l-cystathionine could antagonize mitochondria-mediated human macrophage apoptosis induced by ox-LDL via inhibition of cytc release and caspase activation. PMID:25514411

  8. Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein.

    PubMed

    Thakkar, Shraddha; Wang, Xianwei; Khaidakov, Magomed; Dai, Yao; Gokulan, Kuppan; Mehta, Jawahar L; Varughese, Kottayil I

    2015-01-01

    Atherosclerosis related cardiovascular diseases continue to be the primary cause of mortality in developed countries. The elevated level of low density lipoprotein (LDL) is generally considered to be the driver of atherosclerosis, but recent years have seen a shift in this perception in that the vascular plaque buildup is mainly caused by oxidized LDL (ox-LDL) rather than native-LDL. The scavenger receptor LOX-1 found in endothelial cells binds and internalizes ox-LDL which leads to the initiation of plaque formation in arteries. Using virtual screening techniques, we identified a few potential small molecule inhibitors of LOX-1 and tested their inhibitory potential using differential scanning fluorimetry and various cellular assays. Two of these molecules significantly reduced the uptake of ox-LDL by human endothelial cells, LOX-1 transcription and the activation of ERK1/2 and p38 MAPKs in human endothelial cells. In addition, these molecules suppressed ox-LDL-induced VCAM-1 expression and monocyte adhesion onto human endothelial cells demonstrating their therapeutic potential. PMID:26578342

  9. Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein.

    PubMed

    Thakkar, Shraddha; Wang, Xianwei; Khaidakov, Magomed; Dai, Yao; Gokulan, Kuppan; Mehta, Jawahar L; Varughese, Kottayil I

    2015-11-18

    Atherosclerosis related cardiovascular diseases continue to be the primary cause of mortality in developed countries. The elevated level of low density lipoprotein (LDL) is generally considered to be the driver of atherosclerosis, but recent years have seen a shift in this perception in that the vascular plaque buildup is mainly caused by oxidized LDL (ox-LDL) rather than native-LDL. The scavenger receptor LOX-1 found in endothelial cells binds and internalizes ox-LDL which leads to the initiation of plaque formation in arteries. Using virtual screening techniques, we identified a few potential small molecule inhibitors of LOX-1 and tested their inhibitory potential using differential scanning fluorimetry and various cellular assays. Two of these molecules significantly reduced the uptake of ox-LDL by human endothelial cells, LOX-1 transcription and the activation of ERK1/2 and p38 MAPKs in human endothelial cells. In addition, these molecules suppressed ox-LDL-induced VCAM-1 expression and monocyte adhesion onto human endothelial cells demonstrating their therapeutic potential.

  10. Novel fluorescently labeled peptide compounds for detection of oxidized low-density lipoprotein at high specificity.

    PubMed

    Sato, Akira; Yamanaka, Hikaru; Oe, Keitaro; Yamazaki, Yoji; Ebina, Keiichi

    2014-10-01

    The probes for specific detection of oxidized low-density lipoprotein (ox-LDL) in plasma and in atherosclerotic plaques are expected to be useful for the identification, diagnosis, prevention, and treatment for atherosclerosis. In this study, to develop a fluorescent peptide probe for specific detection of ox-LDL, we investigated the interaction of fluorescein isothiocyanate (FITC)-labeled peptides with ox-LDL using polyacrylamide gel electrophoresis. Two heptapeptides (KWYKDGD and KP6) coupled through the ε-amino group of K at the N-terminus to FITC in the presence/absence of 6-amino-n-caproic acid (AC) linker to FITC--(FITC-AC)KP6 and (FITC)KP6--both bound with high specificity to ox-LDL in a dose-dependent manner. In contrast, a tetrapeptide (YKDG) labeled with FITC at the N-terminus and a pentapeptide (YKDGK) coupled through the ε-amino group of K at the C-terminus to FITC did not bind selectively to ox-LDL. Furthermore, (FITC)KP6 and (FITC-AC)KP6 bound with high specificity to the protein in mouse plasma (probably ox-LDL fraction). These findings strongly suggest that (FITC)KP6 and (FITC-AC)KP6 may be effective novel fluorescent probes for specific detection of ox-LDL.

  11. Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein

    NASA Astrophysics Data System (ADS)

    Thakkar, Shraddha; Wang, Xianwei; Khaidakov, Magomed; Dai, Yao; Gokulan, Kuppan; Mehta, Jawahar L.; Varughese, Kottayil I.

    2015-11-01

    Atherosclerosis related cardiovascular diseases continue to be the primary cause of mortality in developed countries. The elevated level of low density lipoprotein (LDL) is generally considered to be the driver of atherosclerosis, but recent years have seen a shift in this perception in that the vascular plaque buildup is mainly caused by oxidized LDL (ox-LDL) rather than native-LDL. The scavenger receptor LOX-1 found in endothelial cells binds and internalizes ox-LDL which leads to the initiation of plaque formation in arteries. Using virtual screening techniques, we identified a few potential small molecule inhibitors of LOX-1 and tested their inhibitory potential using differential scanning fluorimetry and various cellular assays. Two of these molecules significantly reduced the uptake of ox-LDL by human endothelial cells, LOX-1 transcription and the activation of ERK1/2 and p38 MAPKs in human endothelial cells. In addition, these molecules suppressed ox-LDL-induced VCAM-1 expression and monocyte adhesion onto human endothelial cells demonstrating their therapeutic potential.

  12. Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy.

    PubMed

    Zabirnyk, Olga; Liu, Wei; Khalil, Shadi; Sharma, Anit; Phang, James M

    2010-03-01

    Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy.

  13. Proteome analysis of human monocytic THP-1 cells primed with oxidized low-density lipoproteins.

    PubMed

    Kang, Jeong Han; Kim, Hyun Tae; Choi, Myung-Sook; Lee, Won Ha; Huh, Tae-Lin; Park, Yong Bok; Moon, Byung Jo; Kwon, Oh-Shin

    2006-02-01

    Native low-density lipoprotein (LDL) and oxidized LDL (oxLDL) possess a wide variety of biological properties, and play a central role in atherogenesis. In this study, we used a proteomic analysis of human monocyte THP-1 cells induced with oxLDL or with LDL, to identify proteins potentially involved in atherosclerotic processes. Of the 2500 proteins detected, 93 were differentially expressed as a result of priming with LDL or oxLDL. The proteins were unambiguously identified by comparing the masses of their tryptic peptides with those of all known proteins using MALDI-TOF MS and the NCBI database. The largest differences in expression were observed for vimentin (94-fold increase), meningioma-expressed antigen 6 (48-fold increase), serine/threonine protein phosphatase 2A (40-fold increase), and beta-1,3-galactosyltransferase (15-fold increase). In contrast, the abundance of an unnamed protein product and phosphogluconate dehydrogenase decreased 30-fold and 25-fold, respectively. The expression of some selected proteins was confirmed by Western blot and RT-PCR analyses. The proteins identified in this study are attractive candidates for further biomarker research. This description of the altered protein profiles induced by oxLDL in human monocytes will support functional studies of the macrophage-derived foam cells involved in the pathogenesis of atherosclerosis. PMID:16402358

  14. Effect of Albizia julibrissin water extracts on low-density lipoprotein oxidization.

    PubMed

    Vaughn, Katherine; McClain, Colt; Carrier, Danielle Julie; Wallace, Sunny; King, Jerry; Nagarajan, Shanmugam; Clausen, Edgar

    2007-06-13

    High-value phytochemicals could be extracted from biomass prior to the current cellulosic pretreatment technologies (i.e., lime, ammonia, dilute acid, or pressurized hot water treatments) provided that the extraction is performed with a solvent that is compatible with the pretreatment. This work reports on the extraction of flavonoids from Albizia julibrissin biomass. While extracting A. julibrissin foliage with 50 degrees C water, 2.227 mg/g of hyperoside and 8.134 mg/g quercitrin were obtained, which is in the realm of what was obtained with 60% methanol. A. julibrissin foliage, flower, and whole plant extracts were tested in terms of their potential to inhibit low-density lipoprotein (LDL) oxidization. The highest inhibition was obtained with foliage water extracts, which were standardized at 2.5 microM of flavonoids. Also, the 2.5 microM foliage water extract resulted in a reduction from 43% to only 1% of the observed monocyte adherence. To have commercial application, A. julibrissin water extracts should be devoid of toxicity. The A. julibrissin foliage, flower, and whole plant water extracts were not toxic to Vero 76 cells. In summary, A. julibrissin biomass can be extracted with 50 degrees C water to yield an antioxidant stream, showing that it may be possible to couple extraction of valuable phytochemicals to the cellulosic pretreatment step. PMID:17497875

  15. Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

    SciTech Connect

    Mazière, Cécile; Salle, Valéry; Gomila, Cathy; Mazière, Jean-Claude

    2013-10-18

    Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

  16. Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells.

    PubMed

    Viola, Manuela; Bartolini, Barbara; Vigetti, Davide; Karousou, Evgenia; Moretto, Paola; Deleonibus, Sara; Sawamura, Tatsuya; Wight, Thomas N; Hascall, Vincent C; De Luca, Giancarlo; Passi, Alberto

    2013-10-11

    Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20-50 μg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 ± 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 ± 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 μg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 μg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL.

  17. Role of liver sinusoidal endothelial cells and stabilins in elimination of oxidized low-density lipoproteins

    PubMed Central

    Li, Ruomei; Oteiza, Ana; Sørensen, Karen Kristine; McCourt, Peter; Olsen, Randi; Svistounov, Dmitri

    2011-01-01

    Atherogenesis is associated with elevated levels of low-density lipoprotein (LDL) and its oxidized form (oxLDL) in the blood. The liver is an important scavenger organ for circulating oxLDLs. The present study aimed to examine endocytosis of mildly oxLDL (the major circulating form of oxLDLs) in liver sinusoidal endothelial cells (LSECs) and the involvement of the scavenger receptors stabilin-1 and stabilin-2 in this process. Freshly isolated LSECs, Kupffer cells (KCs), and stabilin-1- and stabilin-2-transfected human embryonic kidney cells were incubated with fluorescently labeled or radiolabeled oxLDLs [oxidized for 3 h (oxLDL3), 6 h, or 24 h (oxLDL24)] to measure endocytosis. The intracellular localization of oxLDLs and stabilins in LSECs was examined by immunofluorescence and immunogold electron microscopy. Whereas oxLDL24 was endocytosed both by LSECs and KCs, oxLDL3 (mildly oxLDL) was taken up by LSECs only. The LSEC uptake of oxLDLs was significantly inhibited by the scavenger receptor ligand formaldehyde-treated serum albumin. Uptake of all modified LDLs was high in stabilin-1-transfected cells, whereas stabilin-2-transfected cells preferentially took up oxLDL24, suggesting that stabilin-1 is a more important receptor for mildly oxLDLs than stabilin-2. Double immunogold labeling experiments in LSECs indicated interactions of stabilin-1 and stabilin-2 with oxLDL3 on the cell surface, in coated pits, and endocytic vesicles. LSECs but not KCs endocytosed mildly oxLDL. Both stabilin-1 and stabilin-2 were involved in the LSEC endocytosis of oxLDLs, but experiments with stabilin-transfected cells pointed to stabilin-1 as the most important receptor for mildly oxLDL. PMID:21030611

  18. Oxidized Low Density Lipoprotein (LDL) Affects Hyaluronan Synthesis in Human Aortic Smooth Muscle Cells*

    PubMed Central

    Viola, Manuela; Bartolini, Barbara; Vigetti, Davide; Karousou, Evgenia; Moretto, Paola; Deleonibus, Sara; Sawamura, Tatsuya; Wight, Thomas N.; Hascall, Vincent C.; De Luca, Giancarlo; Passi, Alberto

    2013-01-01

    Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20–50 μg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 ± 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 ± 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 μg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 μg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL. PMID:23979132

  19. Oxidized low-density lipoprotein is associated with advanced-stage prostate cancer.

    PubMed

    Wan, Fangning; Qin, Xiaojian; Zhang, Guiming; Lu, Xiaolin; Zhu, Yao; Zhang, Hailiang; Dai, Bo; Shi, Guohai; Ye, Dingwei

    2015-05-01

    Clinical and epidemiological data suggest coronary artery disease shares etiology with prostate cancer (PCa). The aim of this work was to assess the effects of several serum markers reported in cardiovascular disease on PCa. Serum markers (oxidized low-density lipoprotein [ox-LDL], apolipoprotein [apo] B100, and apoB48) in peripheral blood samples from 50 patients from Fudan University Shanghai Cancer Center (FUSCC) with localized or lymph node metastatic PCa were investigated in this study. Twenty-five samples from normal individuals were set as controls. We first conducted enzyme-linked immunosorbent assay analysis to select candidate markers that were significantly different between these patients and controls. Then, the clinical relevance between OLR1 (the ox-LDL receptor) expression and PCa was analyzed in The Cancer Genome Atlas (TCGA) cohort. We also investigated the function of ox-LDL in PCa cell lines in vitro. Phosphorylation protein chips were used to analyze cell signaling pathways in ox-LDL-treated PC-3 cells. The ox-LDL level was found to be significantly correlated with N stage of prostate cancer. OLR1 expression was correlated with lymph node metastasis in the TCGA cohort. In vitro, ox-LDL stimulated the proliferation, migration, and invasion of LNCaP and PC-3 in a dose-dependent manner. The results of phosphoprotein microarray illustrated that ox-LDL could influence multiple signaling pathways of PC-3. Activation of proliferation promoting signaling pathways (including β-catenin, cMyc, NF-κB, STAT1, STAT3) as well as apoptosis-associating signaling pathways (including p27, caspase-3) demonstrated that ox-LDL had complicated effects on prostate cancer. Increased serum ox-LDL level and OLR1 expression may indicate advanced-stage PCa and lymph node metastasis. Moreover, ox-LDL could stimulate PCa proliferation, migration, and invasion in vitro.

  20. Proliferation of macrophages due to the inhibition of inducible nitric oxide synthesis by oxidized low-density lipoproteins

    PubMed Central

    Brunner, Monika; Gruber, Miriam; Schmid, Diethart; Baran, Halina; Moeslinger, Thomas

    2015-01-01

    Oxidized low-density lipoprotein (ox-LDL) is assumed to be a major causal agent in hypercholesteraemia-induced atherosclerosis. Because the proliferation of lipid-loaden macrophages within atherosclerotic lesions has been described, we investigated the dependence of macrophage proliferation on the inhibition of inducible nitric oxide synthase (iNOS) by hypochlorite oxidized LDL. Ox-LDL induces a dose dependent inhibition of inducible nitric oxide synthesis in lipopolysaccharide-interferon stimulated mouse macrophages (J774.A1) with concomitant macrophage proliferation as assayed by cell counting, tritiated-thymidine incorporation and measurement of cell protein. Native LDL did not influence macrophage proliferation and inducible nitric oxide synthesis. iNOS protein and mRNA was reduced by HOCl-oxidized LDL (0-40 µg/ml) as revealed by immunoblotting and competitive semiquantitative PCR. Macrophage proliferation was increased by the addition of the iNOS inhibitor L-NAME. The addition of ox-LDL to L-NAME containing incubations induced no further statistically significant increase in cell number. Nitric oxide donors decreased ox-LDL induced macrophage proliferation and nitric oxide scavengers restored macrophage proliferation to the initial values achieved by ox-LDL. The decrease of cytosolic DNA fragments in stimulated macrophages incubated with ox-LDL demonstrates that the proliferative actions of ox-LDL are associated with a decrease of NO-induced apoptosis. Our data show that inhibition of iNOS dependent nitric oxide production caused by hypochlorite oxidized LDL enhances macrophage proliferation. This might be a key event in the pathogenesis of atherosclerotic lesions. PMID:26600745

  1. Oxidized low density lipoprotein suppresses lipopolysaccharide-induced inflammatory responses in microglia: Oxidative stress acts through control of inflammation

    SciTech Connect

    Kim, Ohn Soon; Lee, Chang Seok; Joe, Eun-hye; Jou, Ilo . E-mail: jouilo@ajou.ac.kr

    2006-03-31

    Low density lipoprotein (LDL) is readily oxidized under certain conditions, resulting in the formation of oxidized LDL (oxLDL). Despite numerous in vitro reports that reveal the pathogenic role of oxidative stress, anti-oxidative strategies have underperformed in the clinic. In this study, we examine the role of oxLDL in brain inflammatory responses using cultured rat brain microglia. We demonstrate that oxLDL inhibits lipopolysaccharide (LPS)-induced inflammatory responses in these cells. It also decreases LPS-induced expression of inducible nitric oxide synthase and production of nitric oxide, and reduces LPS-induced secretion of tumor necrosis factor-{alpha} and monocyte chemoattractant protein-1. Oxysterols, known components of oxLDL and endogenous agonists of liver X receptor, can simulate the inhibitory effects of oxLDL in LPS-activated microglia. In addition, their inhibitory effects were mimicked by liver X receptor (LXR) agonists and potentiated by a retinoid X receptor agonist, suggesting these molecules heterodimerize to function as oxysterol receptors. Taken together, our results demonstrate that oxLDL inhibits LPS-induced inflammatory responses in brain microglia and that these inhibitory effects are mediated by oxysterols and, at least in part, by the nuclear receptor LXR. Our results suggest an additional mechanism of action for oxidative stress that acts indirectly via modulation of inflammatory responses. Although further studies are needed, these results answer in part the question of why anti-oxidative strategies have not been successful in clinical situations. Moreover, as brain inflammation participates in the initiation and progression of several neurodegenerative disorders, the present data provide information that should prove a useful guide for designing therapeutic strategies to combat oxidative brain diseases.

  2. Oxidized low density lipoprotein suppresses lipopolysaccharide-induced inflammatory responses in microglia: oxidative stress acts through control of inflammation.

    PubMed

    Kim, Ohn Soon; Lee, Chang Seok; Joe, Eun-hye; Jou, Ilo

    2006-03-31

    Low density lipoprotein (LDL) is readily oxidized under certain conditions, resulting in the formation of oxidized LDL (oxLDL). Despite numerous in vitro reports that reveal the pathogenic role of oxidative stress, anti-oxidative strategies have underperformed in the clinic. In this study, we examine the role of oxLDL in brain inflammatory responses using cultured rat brain microglia. We demonstrate that oxLDL inhibits lipopolysaccharide (LPS)-induced inflammatory responses in these cells. It also decreases LPS-induced expression of inducible nitric oxide synthase and production of nitric oxide, and reduces LPS-induced secretion of tumor necrosis factor-alpha and monocyte chemoattractant protein-1. Oxysterols, known components of oxLDL and endogenous agonists of liver X receptor, can simulate the inhibitory effects of oxLDL in LPS-activated microglia. In addition, their inhibitory effects were mimicked by liver X receptor (LXR) agonists and potentiated by a retinoid X receptor agonist, suggesting these molecules heterodimerize to function as oxysterol receptors. Taken together, our results demonstrate that oxLDL inhibits LPS-induced inflammatory responses in brain microglia and that these inhibitory effects are mediated by oxysterols and, at least in part, by the nuclear receptor LXR. Our results suggest an additional mechanism of action for oxidative stress that acts indirectly via modulation of inflammatory responses. Although further studies are needed, these results answer in part the question of why anti-oxidative strategies have not been successful in clinical situations. Moreover, as brain inflammation participates in the initiation and progression of several neurodegenerative disorders, the present data provide information that should prove a useful guide for designing therapeutic strategies to combat oxidative brain diseases.

  3. Different responses to oxidized low-density lipoproteins in human polarized macrophages

    PubMed Central

    2011-01-01

    Background Oxidized low-density lipoprotein (oxLDL) uptake by macrophages plays an important role in foam cell formation. It has been suggested the presence of heterogeneous subsets of macrophage, such as M1 and M2, in human atherosclerotic lesions. To evaluate which types of macrophages contribute to atherogenesis, we performed cDNA microarray analysis to determine oxLDL-induced transcriptional alterations of each subset of macrophages. Results Human monocyte-derived macrophages were polarized toward the M1 or M2 subset, followed by treatment with oxLDL. Then gene expression levels during oxLDL treatment in each subset of macrophages were evaluated by cDNA microarray analysis and quantitative real-time RT-PCR. In terms of high-ranking upregulated genes and functional ontologies, the alterations during oxLDL treatment in M2 macrophages were similar to those in nonpolarized macrophages (M0). Molecular network analysis showed that most of the molecules in the oxLDL-induced highest scoring molecular network of M1 macrophages were directly or indirectly related to transforming growth factor (TGF)-β1. Hierarchical cluster analysis revealed commonly upregulated genes in all subset of macrophages, some of which contained antioxidant response elements (ARE) in their promoter regions. A cluster of genes that were specifically upregulated in M1 macrophages included those encoding molecules related to nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) signaling pathway. Quantitative real-time RT-PCR showed that the gene expression of interleukin (IL)-8 after oxLDL treatment in M2 macrophages was markedly lower than those in M0 and M1 cells. HMOX1 gene expression levels were almost the same in all 3 subsets of macrophages even after oxLDL treatment. Conclusions The present study demonstrated transcriptional alterations in polarized macrophages during oxLDL treatment. The data suggested that oxLDL uptake may affect TGF-β1- and NF

  4. Effects of oxidized low density lipoprotein on transformation of valvular myofibroblasts to osteoblast-like phenotype.

    PubMed

    Chen, Di; Shen, Ying-Lian; Hu, Wei-Lin; Chen, Zheng-Ping; Li, Yong-Sheng

    2015-06-01

    In order to investigate the roles of Wnt signal pathway in transformation of cardiac valvular myofibroblasts to the osteoblast-like phenotype, the primary cultured porcine aortic valve myofibroblasts were incubated with oxidized low density lipoprotein (ox-LDL, 50 mg/L), and divided into four groups according to the ox-LDL treatment time: control group, ox-LDL 24-h group, ox-LDL 48-h group, and ox-LDL 72-h group. Wnt signal pathway blocker Dickkopf-1 (DDK-1, 100 μg/L) was added in ox-LDL 72-h group. The expression of a-smooth muscle actin (α-SMA), bone morphogenetic protein 2 (BMP2), alkaline phosphatase (ALP), and osteogenic transcription factor Cbfa-1 was detected by Western blotting, and that of β-catenin, a key mediator of Wnt signal pathway by immunocytochemical staining method. The Wnt/β-catenin was observed and the transformation of myofibroblasts to the osteoblast-like phenotype was examined. The expression of α-SMA, BMP2, ALP and Cbfa-1 proteins in the control group was weaker than in the ox-LDL-treated groups. In ox-LDL-treated groups, the protein expression of a-SMA, BMP2, ALP, and Cbfa-1 was significantly increased in a time-dependent manner as compared with the control group, and there was significant difference among the three ox-LDL-treated groups (P<0.05 for all); β-catenin protein was also up-regulated in the ox-LDL-treated groups in a time-dependent manner as compared with the control group (P<0.05), and its transfer from cytoplasm to nucleus and accumulation in the nucleus were increased in the same fashion (P<0.05). After addition of DKK-1, the expression of α-SMA, bone-related proteins and β-catenin protein was significantly reduced as compared with ox-LDL 72-h group (P<0.05). The Wnt/ β-catenin signaling pathway may play an important role in transformation of valvular myofibroblasts to the osteoblast-like phenotype.

  5. Relationship between oxidized low-density lipoprotein antibodies and obesity in different glycemic situations

    PubMed Central

    Babakr, Abdullatif Taha; Elsheikh, Osman Mohamed; Almarzouki, Abdullah A; Assiri, Adel Mohamed; Abdalla, Badr Eldin Elsonni; Zaki, Hani Yousif; Fatani, Samir H; NourEldin, EssamEldin Mohamed

    2014-01-01

    Background Autoantibodies to oxidized low-density lipoprotein (oxLDL) are a heterogeneous group of antibodies that are controversially discussed to be either pathogenic or protective. Biochemical and anthropometric measurements correlated with increased levels of these antibodies are also controversial, especially in conditions of impaired glucose tolerance and type 2 diabetes mellitus. The present study was conducted to evaluate levels of oxLDL antibodies and their correlation with obesity in different glycemic situations. Methods Two hundred and seventy-four adult males were classified into three subgroups: group 1 (n=125), comprising a control group of nondiabetic subjects; group 2 (n=77), comprising subjects with impaired glucose tolerance; and group 3 (n=72), comprising patients with type 2 diabetes mellitus. Body mass index was calculated, and measurement of oxLDL and oxLDL antibodies was performed. Results Higher mean concentrations of oxLDL were found in the type 2 diabetes mellitus and impaired glucose tolerance groups (143.5±21.9 U/L and 108.7±23.7 U/L, respectively). The mean value for the control group was 73.5±27.5 U/L (P<0.001). Higher mean concentrations of anti-oxLDL antibodies were observed in the type 2 diabetes mellitus and impaired glucose tolerance groups (55.7±17.8 U/L and 40.4±17.6 U/L, respectively). The mean value for the control group was 20.4±10 U/L (P<0.001). Levels of anti-oxLDL antibodies were found to be positively and significantly correlated with body mass index in the control group (r=0.46), impaired glucose tolerance (r=0.51), type 2 diabetes mellitus group (r=0.46), and in the whole study population (r=0.44; P<0.001). Conclusion Anti-oxLDL antibody levels were increased in subjects with type 2 diabetes mellitus and impaired glucose tolerance and were positively correlated with obesity and body mass index. PMID:25368528

  6. Spanish sparkling wines (Cavas) as inhibitors of in vitro human low-density lipoprotein oxidation.

    PubMed

    Satué-Gracia, M T; Andrés-Lacueva, C; Lamuela-Raventós, R M; Frankel, E N

    1999-06-01

    Forty-seven dealcoholized sparkling wines (cava) from the Penedès area in Spain were tested for their antioxidant activity in a low-density lipoprotein system. The effect of different quality-related parameters, such as harvest year or grape variety, was investigated. Twenty-two phenolic compounds were separated by high-performance liquid chromatography and identified by comparing their retention time and their ultraviolet spectra with those of pure standards. When tested at the same total phenol concentration, the antioxidant activity of these white sparkling wines was found to be similar to that reported for red wines. This activity was positively correlated with the total phenolic content, trans-caffeic acid, coumaric acid, protocatechuic acid, and quercetin 3-glucuronide. The wines made of the classic cava wine coupage had superior antioxidant activity compared to those of other cultivars.

  7. Endothelial NOS-dependent activation of c-Jun NH(2)- terminal kinase by oxidized low-density lipoprotein

    NASA Technical Reports Server (NTRS)

    Go, Y. M.; Levonen, A. L.; Moellering, D.; Ramachandran, A.; Patel, R. P.; Jo, H.; Darley-Usmar, V. M.

    2001-01-01

    Oxidized low-density lipoprotein (oxLDL) is known to activate a number of signal transduction pathways in endothelial cells. Among these are the c-Jun NH(2)-terminal kinase (JNK), also known as stress-activated protein kinase, and extracellular signal-regulated kinase (ERK). These mitogen-activated protein kinases (MAP kinase) determine cell survival in response to environmental stress. Interestingly, JNK signaling involves redox-sensitive mechanisms and is activated by reactive oxygen and nitrogen species derived from both NADPH oxidases, nitric oxide synthases (NOS), peroxides, and oxidized low-density lipoprotein (oxLDL). The role of endothelial NOS (eNOS) in the activation of JNK in response to oxLDL has not been examined. Herein, we show that on exposure of endothelial cells to oxLDL, both ERK and JNK are activated through independent signal transduction pathways. A key role of eNOS activation through a phosphatidylinositol-3-kinase-dependent mechanism leading to phosphorylation of eNOS is demonstrated for oxLDL-dependent activation of JNK. Moreover, we show that activation of ERK by oxLDL is critical in protection against the cytotoxicity of oxLDL.

  8. Ceruloplasmin enhances smooth muscle cell- and endothelial cell-mediated low density lipoprotein oxidation by a superoxide-dependent mechanism

    NASA Technical Reports Server (NTRS)

    Mukhopadhyay, C. K.; Ehrenwald, E.; Fox, P. L.

    1996-01-01

    Cultured vascular smooth muscle cells (SMC) and endothelial cells (EC) stimulate low density lipoprotein (LDL) oxidation by free radical-mediated, transition metal-dependent mechanisms. The physiological source(s) of metal ions is not known; however, purified ceruloplasmin, a plasma protein containing 7 coppers, oxidizes LDL in vitro. We now show that ceruloplasmin also increases LDL oxidation by vascular cells. In metal ion-free medium, human ceruloplasmin increased bovine aortic SMC- and EC-mediated LDL oxidation by up to 30- and 15-fold, respectively. The maximal response was at 100-300 microg ceruloplasmin/ml, a level at or below the unevoked physiological plasma concentration. Oxidant activity was dependent on protein structure as a specific proteolytic cleavage or removal of one of the seven ceruloplasmin copper atoms inhibited activity. Three lines of evidence indicated a critical role for cellular superoxide (O2.) in ceruloplasmin-stimulated oxidation. First, the rate of production of O2. by cells correlated with their rates of LDL oxidation. Second, superoxide dismutase effectively blocked ceruloplasmin-stimulated oxidation by both cell types. Finally, O2. production by SMC quantitatively accounted for the observed rate of LDL oxidation. To show this, the course of O2. production by SMC was simulated by repeated addition of xanthine and xanthine oxidase to culture medium under cell-free conditions. Neither ceruloplasmin nor O2. alone increased LDL oxidation, but together they completely reconstituted the oxidation rate of ceruloplasmin-stimulated SMC. These results are the first to show that ceruloplasmin stimulates EC- and SMC-mediated oxidation of LDL and that cell-derived O2. accounts quantitatively for metal-dependent, free radical-initiated oxidation of LDL by these cells.

  9. The oxidized low-density lipoprotein receptor mediates vascular effects of inhaled vehicle emissions

    EPA Science Inventory

    Rationale: To determine vascular signaling pathways involved in air pollution (vehicular engine emission) exposure -induced exacerbation of atherosclerosis, associated with onset of clinical cardiovascular events. Objective: To elucidate the role of oxidized LDL (oxLDL) and its ...

  10. Oxidation of Plasmalogen, Low-Density Lipoprotein, and RAW 264.7 Cells by Photoactivatable Atomic Oxygen Precursors

    PubMed Central

    Bourdillon, Max T.; Ford, Benjamin A.; Knulty, Ashley T.; Gray, Colleen N.; Zhang, Miao; Ford, David A.; McCulla, Ryan D.

    2016-01-01

    The oxidation of lipids by endogenous or environmental reactive oxygen species (ROS) generates a myriad of different lipid oxidation products that have important roles in disease pathology. The lipid oxidation products obtained in these reactions is dependent upon the identity of the reacting ROS. The photoinduced deoxygenation of various aromatic heterocyclic oxides has been suggested to generate ground state atomic oxygen (O(3P)) as an oxidant; however, very little is known about reactions between lipids and O(3P). To identify lipid oxidation products arising from the reaction of lipids with O(3P), photoactivatable precursors of O(3P) were irradiated in the presence of lysoplasmenylcholine, low-density lipoprotein, and RAW 264.7 cells under aerobic and anaerobic conditions. Four different aldehyde products consistent with the oxidation of plasmalogens were observed. The four aldehydes were: tetradecanal, pentadecanal, 2-hexadecenal, and hexadecanal. Depending upon the conditions, either pentadecanal or 2-hexadecenal was the major product. Increased amounts of the aldehyde products were observed in aerobic conditions. PMID:27096146

  11. Copper supplementation in humans does not affect the susceptibility of low density lipoprotein to in vitro induced oxidation (FOODCUE project).

    PubMed

    Turley, E; McKeown, A; Bonham, M P; O'Connor, J M; Chopra, M; Harvey, L J; Majsak-Newman, G; Fairweather-Tait, S J; Bügel, S; Sandström, B; Rock, E; Mazur, A; Rayssiguier, Y; Strain, J J

    2000-12-01

    The oxidative modification of low-density lipoprotein cholesterol (LDL) has been implicated in the pathogenesis of atherosclerosis. Copper (Cu) is essential for antioxidant enzymes in vivo and animal studies show that Cu deficiency is accompanied by increased atherogenesis and LDL susceptibility to oxidation. Nevertheless, Cu has been proposed as a pro-oxidant in vivo and is routinely used to induce lipid peroxidation in vitro. Given the dual role of Cu as an in vivo antioxidant and an in vitro pro-oxidant, a multicenter European study (FOODCUE) was instigated to provide data on the biological effects of increased dietary Cu. Four centers, Northern Ireland (coordinator), England, Denmark, and France, using different experimental protocols, examined the effect of Cu supplementation (3 or 6 mg/d) on top of normal Cu dietary intakes or Cu-controlled diets (0.7/1.6/6.0 mg/d), on Cu-mediated and peroxynitrite-initiated LDL oxidation in apparently healthy volunteers. Each center coordinated its own supplementation regimen and all samples were subsequently transported to Northern Ireland where lipid peroxidation analysis was completed. The results from all centers showed that dietary Cu supplementation had no effect on Cu- or peroxynitrite-induced LDL susceptibility to oxidation. These data show that high intakes (up to 6 mg Cu) for extended periods do not promote LDL susceptibility to in vitro-induced oxidation. PMID:11121720

  12. Macrophage Differentiation from Monocytes Is Influenced by the Lipid Oxidation Degree of Low Density Lipoprotein.

    PubMed

    Seo, Jin-Won; Yang, Eun-Jeong; Yoo, Kyung-Hwa; Choi, In-Hong

    2015-01-01

    LDL plays an important role in atherosclerotic plaque formation and macrophage differentiation. However, there is no report regarding the oxidation degree of LDL and macrophage differentiation. Our study has shown that the differentiation into M1 or M2 macrophages is related to the lipid oxidation level of LDL. Based on the level of lipid peroxidation, LDL is classified into high-oxidized LDL (hi-oxLDL) and low-oxidized LDL (low-oxLDL). The differentiation profiles of macrophages were determined by surface receptor expression and cytokine secretion profiles. Low-oxLDL induced CD86 expression and production of TNF-α and IL-12p40 in THP-1 cells, indicating an M1 macrophage phenotype. Hi-oxLDL induced mannose receptor expression and production of IL-6 and monocyte chemoattractant protein-1, which mostly match the phenotype of M2 macrophages. Further supporting evidence for an M2 polarization by hi-oxLDL was the induction of LOX-1 in THP-1 cells treated with hi-oxLDL but not with low-oxLDL. Similar results were obtained in primary human monocytes. Therefore, our results strongly suggest that the oxidation degree of LDL influences the differentiation of monocytes into M1 or M2 macrophages and determines the inflammatory fate in early stages of atherosclerosis. PMID:26294848

  13. Macrophage Differentiation from Monocytes Is Influenced by the Lipid Oxidation Degree of Low Density Lipoprotein

    PubMed Central

    Seo, Jin-Won; Yang, Eun-Jeong; Yoo, Kyung-Hwa; Choi, In-Hong

    2015-01-01

    LDL plays an important role in atherosclerotic plaque formation and macrophage differentiation. However, there is no report regarding the oxidation degree of LDL and macrophage differentiation. Our study has shown that the differentiation into M1 or M2 macrophages is related to the lipid oxidation level of LDL. Based on the level of lipid peroxidation, LDL is classified into high-oxidized LDL (hi-oxLDL) and low-oxidized LDL (low-oxLDL). The differentiation profiles of macrophages were determined by surface receptor expression and cytokine secretion profiles. Low-oxLDL induced CD86 expression and production of TNF-α and IL-12p40 in THP-1 cells, indicating an M1 macrophage phenotype. Hi-oxLDL induced mannose receptor expression and production of IL-6 and monocyte chemoattractant protein-1, which mostly match the phenotype of M2 macrophages. Further supporting evidence for an M2 polarization by hi-oxLDL was the induction of LOX-1 in THP-1 cells treated with hi-oxLDL but not with low-oxLDL. Similar results were obtained in primary human monocytes. Therefore, our results strongly suggest that the oxidation degree of LDL influences the differentiation of monocytes into M1 or M2 macrophages and determines the inflammatory fate in early stages of atherosclerosis. PMID:26294848

  14. Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia.

    PubMed

    Razavi, Seyed-Mostafa; Gholamin, Sharareh; Eskandari, Ali; Mohsenian, Nakta; Ghorbanihaghjo, Amir; Delazar, Abbas; Rashtchizadeh, Nadereh; Keshtkar-Jahromi, Maryam; Argani, Hassan

    2013-03-01

    Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (-10.68±26.76 mg/dL, P=.015), LDL cholesterol (-9.66±23.92 mg/dL, P=.014), and Ox-LDL (-5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals.

  15. Serum amyloid A stimulates macrophage foam cell formation via lectin-like oxidized low-density lipoprotein receptor 1 upregulation

    SciTech Connect

    Lee, Ha Young; Kim, Sang Doo; Baek, Suk-Hwan; Choi, Joon Hyuk; Cho, Kyung-Hyun; Zabel, Brian A.; Bae, Yoe-Sik

    2013-03-29

    Highlights: ► SAA induced macrophage foam cell formation. ► SAA stimulated upregulation of lectin-like oxidized low-density lipoprotein receptor 1 (LOX1). ► SAA-induced LOX1 expression and foam cell formation is mediated by JNK/NF-κB signaling. ► HDL-conjugated SAA also stimulates foam cell formation via LOX1 upregulation. ► The finding reveals a novel mechanism of action of SAA in the pathogenesis of atherosclerosis. -- Abstract: Elevated levels of serum amyloid A (SAA) is a risk factor for cardiovascular diseases, however, the role of SAA in the pathophysiology of atherosclerosis remains unclear. Here we show that SAA induced macrophage foam cell formation. SAA-stimulated foam cell formation was mediated by c-jun N-terminal kinase (JNK) signaling. Moreover, both SAA and SAA-conjugated high density lipoprotein stimulated the expression of the important scavenger receptor lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) via nuclear factor-κB (NF-κB). A LOX1 antagonist carrageenan significantly blocked SAA-induced foam cell formation, indicating that SAA promotes foam cell formation via LOX1 expression. Our findings therefore suggest that SAA stimulates foam cell formation via LOX1 induction, and thus likely contributes to atherogenesis.

  16. Luteolin-rich artichoke extract protects low density lipoprotein from oxidation in vitro.

    PubMed

    Brown, J E; Rice-Evans, C A

    1998-09-01

    Flavonoids represent a diverse group of phytochemicals which possess the capacity to act as antioxidants in vitro. This study examined the free radical scavenging properties of a luteolin-rich artichoke extract and some of its pure flavonoid constituents by assessing their ability to prevent Cu2+-mediated LDL oxidation. Artichoke extract retarded LDL oxidation in a dose-dependent manner as measured by a prolongation of the lag phase to conjugated diene formation, a decrease in the rate of propagation and a sparing of endogenous LDL alpha-tocopherol during oxidation. The pure aglycone, luteolin (1 microM), demonstrated an efficacy similar to that of 20 microg/ml artichoke extract in inhibiting lipid peroxidation. Luteolin-7-O-glucoside, one of the glycosylated forms in the diet, also demonstrated a dose-dependent reduction of LDL oxidation that was less effective than that of luteolin. Studies of the copper-chelating properties of luteolin-7-O-glucoside and luteolin suggest a potential role for chelation in the antioxidative effects of artichoke extract. Overall, the results demonstrate that the antioxidant activity of the artichoke extract relates in part to its constituent flavonoids which act as hydrogen donors and metal ion chelators, and the effectiveness is further influenced by their partitioning between aqueous and lipophilic phases. PMID:9802556

  17. Effect of concentrated red grape juice consumption on serum antioxidant capacity and low-density lipoprotein oxidation.

    PubMed

    Day, A P; Kemp, H J; Bolton, C; Hartog, M; Stansbie, D

    1997-01-01

    This study examines whether the beneficial antioxidant effects of red wine can be reproduced by nonalcoholic red grape juice concentrate. Seven subjects consumed 125 ml concentrate daily for 7 days. Following first ingestion there was a rise in serum total antioxidant capacity (TAC) from 441 to 478 mumol/l at 60 min (p < 0.005). On day 8, TAC was 50 mumol/l higher than at baseline (p < 0.05). There was reduced susceptibility of low-density lipoprotein (LDL) to oxidation. Red grape juice concentrate ingestion results in increased serum antioxidant capacity and protection of LDL from oxidation and thus nonalcoholic red grape extract may have similar beneficial effects to red wine.

  18. Oxidative susceptibility of low density lipoprotein subfractions is related to their ubiquinol-10 and alpha-tocopherol content.

    PubMed

    Tribble, D L; van den Berg, J J; Motchnik, P A; Ames, B N; Lewis, D M; Chait, A; Krauss, R M

    1994-02-01

    The conjugated polyene fatty acid parinaric acid (PnA) undergoes a stoichiometric loss in fluorescence upon oxidation and can be used to directly monitor peroxidative stress within lipid environments. We evaluated the course of potentially atherogenic oxidative changes in low density lipoproteins (LDL) by monitoring the oxidation of PnA following its incorporation into buoyant (p = 1.026-1.032 g/ml) and dense (p = 1.040-1.054 g/ml) LDL subfractions. Copper-induced oxidation of LDL-associated PnA exhibited an initial lag phase followed by an increased rate of loss until depletion. Increased PnA oxidation occurred immediately after the antioxidants ubiquinol-10 and alpha-tocopherol were consumed but before there were marked elevations in conjugated dienes. Despite differences in sensitivity to early oxidation events, PnA oxidation and conjugated diene lag times were correlated (r = 0.582; P = 0.03), and both indicated a greater susceptibility of dense than buoyant LDL in accordance with previous reports. The greater susceptibility of PnA in dense LDL was attributed to reduced levels of ubiquinol-10 and alpha-tocopherol, which were approximately 50% lower than in buoyant LDL (mol of antioxidant/mol of LDL) and together accounted for 80% of the variation in PnA oxidation lag times. These results suggest that PnA is a useful probe of LDL oxidative susceptibility and may be superior to conjugated dienes for monitoring the initial stages of LDL lipid peroxidation. Differences in oxidative susceptibility among LDL density subfractions are detected by the PnA assay and are due in large part to differences in their antioxidant content.

  19. Antioxidant Effects of Vitamins C and E on the Low-Density Lipoprotein Oxidation Mediated by Myeloperoxidase

    PubMed Central

    Samsam Shariat, Seyed Ziyae Aldin; Mostafavi, Sayed Abolfazl; Khakpour, Farzad

    2013-01-01

    Background: Oxidative modification of low-density lipoprotein (LDL) appears to be an early step in the pathogenesis of atherosclerosis. Meanwhile, myeloperoxidase (MPO)-catalyzed reaction is one of the potent pathways for LDL oxidation in vivo. The aim of this study was to evaluate in vitro antioxidant effects of vitamins C and E on LDL oxidation mediated by MPO. Methods: MPO was isolated from fresh plasma by sequential centrifugation using density ultracentrifugation. It was incubated with LDL and the LDL oxidation level was determined spectrophotometrically by measuring conjugated diene absorbance at 234 nm. Furthermore, vitamin C (50-200 mM) and vitamin E (10-40 mM) were added and the LDL oxidation level was determined. Results: The purity index of MPO and its enzymatic activity were 0.69 and 1127 U/mg protein, respectively. It was demonstrated that vitamin C in vitro inhibited LDL oxidation mediated by MPO; however, vitamin E was unable to act in the same way. The protection by vitamin C was concentration dependent and maximum protective effect of vitamin C was observed at 150 mM, where about 64% of the LDL oxidation was inhibited. Vitamin C increased lag time of LDL oxidation mediated by MPO up to 2.4 times. Conclusion: It can be concluded from our results that vitamin C is able to improve LDL resistance to oxidative modification in vitro. In addition, vitamin C might be effective in LDL oxidation mediated by MPO in vivo, resulting in reduction of atherosclerosis process rate. PMID:23279831

  20. Role of Lectin-Like Oxidized Low Density Lipoprotein-1 in Fetoplacental Vascular Dysfunction in Preeclampsia

    PubMed Central

    Zuniga, Felipe A.; Ormazabal, Valeska; Gutierrez, Nicolas; Aguilera, Valeria; Radojkovic, Claudia; Veas, Carlos; Escudero, Carlos; Lamperti, Liliana; Aguayo, Claudio

    2014-01-01

    The bioavailability of nitric oxide (NO) represents a key marker in vascular health. A decrease in NO induces a pathological condition denominated endothelial dysfunction, syndrome observed in different pathologies, such as obesity, diabetes, kidney disease, cardiovascular disease, and preeclampsia (PE). PE is one of the major risks for maternal death and fetal loss. Recent studies suggest that the placenta of pregnant women with PE express high levels of lectin-like oxidized LDL receptor-1 (LOX-1), which induces endothelial dysfunction by increasing reactive oxygen species (ROS) and decreasing intracellular NO. Besides LOX-1 activation induces changes in migration and apoptosis of syncytiotrophoblast cells. However, the role of this receptor in placental tissue is still unknown. In this review we will describes the physiological roles of LOX-1 in normal placenta development and the potential involvement of this receptor in the pathophysiology of PE. PMID:25110674

  1. Oxidative susceptibility of low density lipoprotein from rabbits fed atherogenic diets containing coconut, palm, or soybean oils.

    PubMed

    Yap, S C; Choo, Y M; Hew, N F; Yap, S F; Khor, H T; Ong, A S; Goh, S H

    1995-12-01

    The oxidative susceptibilities of low density lipoproteins (LDL) isolated from rabbits fed high-fat atherogenic diets containing coconut, palm, or soybean oil were investigated. New Zealand white rabbits were fed atherogenic semisynthetic diets containing 0.5% cholesterol and either (i) 13% coconut oil and 2% corn oil (CNO), (ii) 15% refined, bleached, and deodorized palm olein (RBDPO), (iii) 15% crude palm olein (CPO), (iv) 15% soybean oil (SO), or (v) 15% refined, bleached, and deodorized palm olein without cholesterol supplementation [RBDPO(wc)], for a period of twelve weeks. Total fatty acid compositions of the plasma and LDL were found to be modulated (but not too drastically) by the nature of the dietary fats. Cholesterol supplementation significantly increased the plasma level of vitamin E and effectively altered the plasma composition of long-chain fatty acids in favor of increasing oleic acid. Oxidative susceptibilities of LDL samples were determined by Cu2(+)-catalyzed oxidation which provide the lag times and lag-phase slopes. The plasma LDL from all palm oil diets [RBDPO, CPO, and RBDPO(wc)] were shown to be equally resistant to the oxidation, and the LDL from SO-fed rabbits were most susceptible, followed by the LDL from the CNO-fed rabbits. These results reflect a relationship between the oxidative susceptibility of LDL due to a combination of the levels of polyunsaturated fatty acids and vitamin E.

  2. Effects of flow on LOX-1 and oxidized low-density lipoprotein interactions in brain endothelial cell cultures.

    PubMed

    Mao, Xiaoou; Xie, Lin; Greenberg, David A

    2015-12-01

    Fluid shear stress and uptake of oxidized low-density lipoprotein (ox-LDL) into the vessel wall both contribute to atherosclerosis, but the relationship between shear stress and ox-LDL uptake is unclear. We examined the effects of flow, induced by orbital rotation of bEnd.3 brain endothelial cell cultures for 1 wk, on ox-LDL receptor (LOX-1) protein expression, ox-LDL uptake and ox-LDL toxicity. Orbitally rotated cultures showed no changes in LOX-1 protein expression, ox-LDL uptake or ox-LDL toxicity, compared to stationary cultures. Flow alone does not modify ox-LDL/LOX-1 signaling in bEnd.3 brain endothelial cells in vitro, suggesting that susceptibility of atheroprone vascular sites to lipid accumulation is not due solely to effects of altered flow on endothelium. PMID:26462413

  3. Effects of flow on LOX-1 and oxidized low-density lipoprotein interactions in brain endothelial cell cultures.

    PubMed

    Mao, Xiaoou; Xie, Lin; Greenberg, David A

    2015-12-01

    Fluid shear stress and uptake of oxidized low-density lipoprotein (ox-LDL) into the vessel wall both contribute to atherosclerosis, but the relationship between shear stress and ox-LDL uptake is unclear. We examined the effects of flow, induced by orbital rotation of bEnd.3 brain endothelial cell cultures for 1 wk, on ox-LDL receptor (LOX-1) protein expression, ox-LDL uptake and ox-LDL toxicity. Orbitally rotated cultures showed no changes in LOX-1 protein expression, ox-LDL uptake or ox-LDL toxicity, compared to stationary cultures. Flow alone does not modify ox-LDL/LOX-1 signaling in bEnd.3 brain endothelial cells in vitro, suggesting that susceptibility of atheroprone vascular sites to lipid accumulation is not due solely to effects of altered flow on endothelium.

  4. Effect of garlic supplementation on oxidized low density lipoproteins and lipid peroxidation in patients of essential hypertension.

    PubMed

    Dhawan, Veena; Jain, Sanjay

    2004-11-01

    Reactive oxygen species (ROS) has been implicated in the pathogenesis of many diseases including hypertension. Therefore, certain compounds with antioxidative capacity are believed to be protective against such diseases. Some components of garlic are known to possess antioxidative properties. Therefore, in the present study we investigated the effect of short-term garlic supplementation in essential hypertensive patients (EH) on indices of oxidative stress. Twenty patients of EH as diagnosed by JNC VI criteria (Group I) and 20 age and sex-matched normotensive controls were enrolled for the study. Both groups were given garlic pearls (GP) in a dose of 250 mg per day for 2 months. Baseline samples were obtained at start of the study, i.e. 0 day, and thereafter, 2 months (follow-up). Lipids and lipoprotein subfractions, plasma-oxidized low-density lipoproteins (ox-LDL), plasma and urinary concentration of 8-iso-Prostaglandin F2alpha (8-iso-PGF2alpha) as a biomarker of oxidative stress in vivo, and the total antioxidant status (TOS) of these individuals were determined. We observed a moderate hypercholesterolemia and a significantly raised blood pressure in hypertensive patients as compared to the controls. The indices of oxidative stress, i.e. plasma ox-LDL and plasma and urinary concentration of 8-iso-PGF2alpha were significantly increased in EH group. Further, hypertensive patients had a significantly low TOS as compared to the control group. With in 2 months of GP supplementation, there was a significant decline in both systolic (SBP) and diastolic blood pressures (DBP) and a significant reduction in ox-LDL and 8-iso-PGF2alpha levels in Group I patients. Further, a moderate increase in the TOS was also observed in this group as compared to their control counterparts. These findings suggest that dietary supplementation of garlic may be beneficial in reducing blood pressure and oxidative stress in hypertensive individuals. PMID:15646031

  5. Oxidized Low-Density Lipoprotein Contributes to Atherogenesis via Co-activation of Macrophages and Mast Cells

    PubMed Central

    Chen, Chong; Khismatullin, Damir B.

    2015-01-01

    Oxidized low-density lipoprotein (OxLDL) is a risk factor for atherosclerosis, due to its role in endothelial dysfunction and foam cell formation. Tissue-resident cells such as macrophages and mast cells release inflammatory mediators upon activation that in turn cause endothelial activation and monocyte adhesion. Two of these mediators are tumor necrosis factor (TNF)-α, produced by macrophages, and histamine, produced by mast cells. Static and microfluidic flow experiments were conducted to determine the number of adherent monocytes on vascular endothelium activated by supernatants of oxLDL-treated macrophages and mast cells or directly by oxLDL. The expression of adhesion molecules on activated endothelial cells and the concentration of TNF-α and histamine in the supernatants were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. A low dose of oxLDL (8 μg/ml), below the threshold for the clinical presentation of coronary artery disease, was sufficient to activate both macrophages and mast cells and synergistically increase monocyte-endothelium adhesion via released TNF-α and histamine. The direct exposure of endothelial cells to a much higher dose of oxLDL (80 μg/ml) had less effect on monocyte adhesion than the indirect activation via oxLDL-treated macrophages and mast cells. The results of this work indicate that the co-activation of macrophages and mast cells by oxLDL is an important mechanism for the endothelial dysfunction and atherogenesis. The observed synergistic effect suggests that both macrophages and mast cells play a significant role in early stages of atherosclerosis. Allergic patients with a lipid-rich diet may be at high risk for cardiovascular events due to high concentration of low-density lipoprotein and histamine in arterial vessel walls. PMID:25811595

  6. Activation of sonic hedgehog signaling attenuates oxidized low-density lipoprotein-stimulated brain microvascular endothelial cells dysfunction in vitro.

    PubMed

    Jiang, Xiu-Long; Chen, Ting; Zhang, Xu

    2015-01-01

    The study was performed to investigate the role of sonic hedgehog (SHH) in the oxidized low-density lipoprotein (oxLDL)-induced blood-brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to oxLDL. The results indicated that treatment of MBMECs with oxLDL decreased the cell viability, and oxidative stress was involved in oxLDL-induce MBMECs dysfunction with increasing intracellular ROS and MDA formation as well as decreasing NO release and eNOS mRNA expression. In addition, SHH signaling components, such as SHH, Smo and Gli1, mRNA and protein levels were significantly decreased after incubation with increasing concentrations of oxLDL. Treatment with oxLDL alone or SHH loss-of-function significantly increased the permeability of MBMECs, and overexpression of SHH attenuated oxLDL-induced elevation of permeability in MBMECs. Furthermore, SHH gain-of-function could reverse oxLDL-induced apoptosis through inhibition caspase3 and caspase8 levels in MBMECs. Taken together, these results demonstrated that the suppression of SHH in MBMECs might contribute to the oxLDL-induced disruption of endothelial barrier. However, the overexpression of SHH could reverse oxLDL-induced endothelial cells dysfunction in vitro.

  7. Oxidised low density lipoprotein causes human macrophage cell death through oxidant generation and inhibition of key catabolic enzymes.

    PubMed

    Katouah, Hanadi; Chen, Alpha; Othman, Izani; Gieseg, Steven P

    2015-10-01

    Oxidised low density lipoprotein (oxLDL) is thought to be a significant contributor to the death of macrophage cells observed in advanced atherosclerotic plaques. Using human-derived U937 cells we have examined the effect of cytotoxic oxLDL on oxidative stress and cellular catabolism. Within 3h of the addition of oxLDL, there was a rapid, concentration dependent rise in cellular reactive oxygen species followed by the loss of cellular GSH, and the enzyme activity of both glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and aconitase. The loss of these catabolic enzymes was accompanied by the loss of cellular ATP and lower lactate generation. Addition of the macrophage antioxidant 7,8-dihydroneopterin inhibited the ROS generation, glutathione loss and catabolic inactivation. NOX was shown to be activated by oxLDL addition while apocynin inhibited the loss of GSH and cell viability. The data suggests that oxLDL triggers an excess of ROS production through NOX activation, and catabolic failure through thiol oxidation resulting in cell death.

  8. Activation of sonic hedgehog signaling attenuates oxidized low-density lipoprotein-stimulated brain microvascular endothelial cells dysfunction in vitro.

    PubMed

    Jiang, Xiu-Long; Chen, Ting; Zhang, Xu

    2015-01-01

    The study was performed to investigate the role of sonic hedgehog (SHH) in the oxidized low-density lipoprotein (oxLDL)-induced blood-brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to oxLDL. The results indicated that treatment of MBMECs with oxLDL decreased the cell viability, and oxidative stress was involved in oxLDL-induce MBMECs dysfunction with increasing intracellular ROS and MDA formation as well as decreasing NO release and eNOS mRNA expression. In addition, SHH signaling components, such as SHH, Smo and Gli1, mRNA and protein levels were significantly decreased after incubation with increasing concentrations of oxLDL. Treatment with oxLDL alone or SHH loss-of-function significantly increased the permeability of MBMECs, and overexpression of SHH attenuated oxLDL-induced elevation of permeability in MBMECs. Furthermore, SHH gain-of-function could reverse oxLDL-induced apoptosis through inhibition caspase3 and caspase8 levels in MBMECs. Taken together, these results demonstrated that the suppression of SHH in MBMECs might contribute to the oxLDL-induced disruption of endothelial barrier. However, the overexpression of SHH could reverse oxLDL-induced endothelial cells dysfunction in vitro. PMID:26722472

  9. Z-Scan Analysis: a New Method to Determine the Oxidative State of Low-Density Lipoprotein and Its Association with Multiple Cardiometabolic Biomarkers

    NASA Astrophysics Data System (ADS)

    de Freitas, Maria Camila Pruper; Figueiredo Neto, Antonio Martins; Giampaoli, Viviane; da Conceição Quintaneiro Aubin, Elisete; de Araújo Lima Barbosa, Milena Maria; Damasceno, Nágila Raquel Teixeira

    2016-04-01

    The great atherogenic potential of oxidized low-density lipoprotein has been widely described in the literature. The objective of this study was to investigate whether the state of oxidized low-density lipoprotein in human plasma measured by the Z-scan technique has an association with different cardiometabolic biomarkers. Total cholesterol, high-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A-I and apolipoprotein B, paraoxonase-1, and glucose were analyzed using standard commercial kits, and low-density lipoprotein cholesterol was estimated using the Friedewald equation. A sandwich enzyme-linked immunosorbent assay was used to detect electronegative low-density lipoprotein. Low-density lipoprotein and high-density lipoprotein sizes were determined by Lipoprint® system. The Z-scan technique was used to measure the non-linear optical response of low-density lipoprotein solution. Principal component analysis and correlations were used respectively to resize the data from the sample and test association between the θ parameter, measured with the Z-scan technique, and the principal component. A total of 63 individuals, from both sexes, with mean age 52 years (±11), being overweight and having high levels of total cholesterol and low levels of high-density lipoprotein cholesterol, were enrolled in this study. A positive correlation between the θ parameter and more anti-atherogenic pattern for cardiometabolic biomarkers together with a negative correlation for an atherogenic pattern was found. Regarding the parameters related with an atherogenic low-density lipoprotein profile, the θ parameter was negatively correlated with a more atherogenic pattern. By using Z-scan measurements, we were able to find an association between oxidized low-density lipoprotein state and multiple cardiometabolic biomarkers in samples from individuals with different cardiovascular risk factors.

  10. Tartaric Acid-based Amphiphilic Macromolecules with Ether Linkages Exhibit Enhanced Repression of Oxidized Low Density Lipoprotein Uptake

    PubMed Central

    Abdelhamid, Dalia; Zhang, Yingue; Lewis, Daniel R.; Moghe, Prabhas V.; Welsh, William J.; Uhrich, Kathryn E.

    2015-01-01

    Cardiovascular disease initiates with the atherogenic cascade of scavenger receptor- (SR-) mediated oxidized low-density lipoprotein (oxLDL) uptake. Resulting foam cell formation leads to lipid-rich lesions within arteries. We designed amphiphilic macromolecules (AMs) to inhibit these processes by competitively blocking oxLDL uptake via SRs, potentially arresting atherosclerotic development. In this study, we investigated the impact of replacing ester linkages with ether linkages in the AM hydrophobic domain. We hypothesized that ether linkages would impart flexibility for orientation to improve binding to SR binding pockets, enhancing anti-atherogenic activity. A series of tartaric acid-based AMs with varying hydrophobic chain lengths and conjugation chemistries were synthesized, characterized, and evaluated for bioactivity. 3-D conformations of AMs in aqueous conditions may have significant effects on anti-atherogenic potency and were simulated by molecular modeling. Notably, ether-linked AMs exhibited significantly higher levels of inhibition of oxLDL uptake than their corresponding ester analogues, indicating a dominant effect of linkage flexibility on pharmacological activity. The degradation stability was also enhanced for ether-linked AMs. These studies further suggested that alkyl chain length (i.e., relative hydrophobicity), conformation (i.e., orientation), and chemical stability play a critical role in modulating oxLDL uptake, and guide the design of innovative cardiovascular therapies. PMID:25890704

  11. Characterization of a receptor for oxidized low-density lipoproteins on rat Kupffer cells: similarity to macrosialin.

    PubMed Central

    Van Velzen, A G; Da Silva, R P; Gordon, S; Van Berkel, T J

    1997-01-01

    Rat liver Kupffer cell membranes contain a protein that recognizes specifically oxidized low-density lipoproteins (oxLDL). Visualization after blotting under reducing conditions indicates that the receptor is a monomeric protein, with an estimated molecular mass of 115-120 kDa. N-Glycosidase F and endoglycosidase F treatment resulted in a fall in estimated molecular mass of 24 and 11 kDa respectively, whereas O-glycosidase was ineffective. No effect on the extent of interaction with oxLDL was noticed, suggesting that glycans are not essential for ligand recognition. Using a polyclonal antibody to mouse macrosialin, we visualized macrosialin on blot, and compared this glycoprotein with the oxLDL-binding protein. It appears that the two glycoproteins have a similar molecular mass and are comparably affected by treatment with the different glycosidases. Incubation with trypsin resulted in a reduction in the estimated molecular mass of about 25 kDa for both the oxLDL-binding protein and macrosialin. These results indicate that the oxLDL-binding protein and macrosialin are identical, suggesting a role for macrosialin in modified LDL catabolism. PMID:9065757

  12. Olmesartan Attenuates the Impairment of Endothelial Cells Induced by Oxidized Low Density Lipoprotein through Downregulating Expression of LOX-1

    PubMed Central

    Zhang, Hua; Ma, Genshan; Yao, Yuyu; Qian, Huidong; Li, Weizhang; Chen, Xinjun; Jiang, Wenlong; Zheng, Ruolong

    2012-01-01

    Oxidized low density lipoprotein (ox-LDL) and its receptor, lectin-Like ox-LDL receptor-1 (LOX-1), play important roles in the development of endothelial injuries. Olmesartan can protect endothelial cells from the impairment caused by various pathological stimulations. In the present study we investigated whether olmesartan decreased the impairment of endothelial cells induced by ox-LDL by exerting its effects on LOX-1 both in vitro and in vivo. Incubation of cultured endothelial cells of neonatal rats with ox-LDL for 24 h or infusion of ox-LDL in mice for 3 weeks led to the remarkable impairment of endothelial cells, including increased lactate dehydrogenase synthesis, phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK) and expression of apoptotic genes such as B-cell leukemia/lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3. Simultaneously, the cell vitality and expression of Bcl-2 gene were greatly reduced. All these effects, however, were significantly suppressed by the treatment with olmesartan. Furthermore, ox-LDL promoted up-regulation of LOX-1 expression either in cultured endothelial cells or in the aortas of mice, which was reversed with the administration of olmesartan. Our data indicated that olmesartan may attenuate the impairment of endothelial cell via down-regulation of the increased LOX-1 expression induced by ox-LDL. PMID:22408405

  13. Protective effect of rosuvastatin treatment by regulating oxidized low-density lipoprotein expression in a rat model of liver fibrosis

    PubMed Central

    Yu, Shuiping; Zhou, Xueling; Hou, Bingzong; Tang, Bo; Li, Jian; Zhang, Baimeng

    2016-01-01

    The present study aimed to evaluate the protective effect of rosuvastatin treatment on the mechanism of oxidized low-density lipoprotein (Ox-LDL) in rats with liver fibrosis. In total, 72 male Sprague-Dawley rats were divided into 3 groups: 24 in the control group (A), 24 in the obstructive jaundice models group (B) and 24 in the rosuvastatin group (C). Each group was further divided into four subgroups for assessment at different time-points. The obstructive jaundice models were established and rosuvastatin was administered by gavage. Liver fibrosis indicators, Ox-LDL, malonaldehyde (MDA) and superoxide dismutase (SOD), were measured and liver pathological changes were observed at weeks 1, 2, 3 and 4 after model induction. In groups B and C, the rat models were successfully established, and there were significant changes in the expression of Ox-LDL and the three liver fibrosis indicators when compared to group A (P<0.01). However, the expression of Ox-LDL and the three liver fibrosis indicators in group C were decreased compared with group B (P<0.05), while SOD increased (P<0.05) and MDA decreased (P<0.05). The three liver fibrosis indicators were different in comparison to group B (P<0.05). Thus, there appeared to be an association between the expression of Ox-LDL and liver fibrosis. Treatment with rosuvastatin could regulate the expression of Ox-LDL and improve liver fibrosis in rat models with obstructive jaundice. PMID:27588174

  14. Effect of lycopene on the copper-induced oxidation of low-density lipoprotein in broiler chickens.

    PubMed

    Lee, Kyung-Woo; Choo, Won-Don; Kang, Chang-Won; An, Byoung-Ki

    2016-01-01

    The present study was undertaken to investigate whether dietary lycopene (LP) could prevent the copper-mediated oxidation of low density lipoprotein (LDL), and affect growth performance, relative organ weights, plasma and meat lipid profiles, and LP contents in plasma and tissues in broiler chickens. A total of 160 day-old male broiler chicks were randomly allotted into 16 pens with rice husk as a bedding material. Each experiment had 4 replicates, 10 chicks per replicate (n = 4 per treatment). A corn-soybean meal base diet was used as a control diet (CONT). To formulate the experimental diets, the base diet was added with LP at the levels of 10 (LP10) or 20 mg/kg (LP20), or 17 g/kg of tomato paste (TP17) which was equivalent to 5 ppm of LP. The experiment lasted 4 weeks. Growth performance and relative organ weights were not affected (p > 0.05) by any of dietary treatments. Dietary LP significantly lowered (p < 0.05) triglyceride and LDL cholesterol at 2 weeks of age, but did not affect them at 4 weeks of age. Total cholesterol in thigh meats was not altered by dietary treatments. LP was not detected in leg meats in all chicks, nor in liver or plasma of the CONT group. LP was found in liver and plasma, being the former greater in the concentration, of the chicks fed diets containing LP10, LP20, or TP17. At 2 and 4 weeks, the copper-mediated oxidation of LDL was delayed (p < 0.05) in either LP- or TP-fed chickens compared with the CONT group. In conclusion, LP lowers triglyceride and LDL cholesterol, is deposited into serum and liver, and prevents the LDL oxidation in broiler chickens, confirming the role of LP in the lipid-lowering and antioxidant properties in broiler chickens. PMID:27047715

  15. Association between soluble lectin-like oxidized low-density lipoprotein receptor 1 levels and coronary slow flow phenomenon

    PubMed Central

    Caglar, Ilker Murat; Ozde, Cem; Caglar, Fatma Nihan Turhan; Akturk, Ibrahim Faruk; Ugurlucan, Murat; Karakaya, Osman

    2016-01-01

    Introduction The coronary slow flow phenomenon (CSFP) has been associated with myocardial ischemia, myocardial infarction, life-threatening arrhythmias, sudden cardiac death and increased cardiovascular mortality similar to coronary artery disease (CAD). Possible underlying mechanisms of CSFP are endothelial dysfunction, chronic inflammation, microvascular dysfunction and diffuse atherosclerosis. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) seems to play an important role in the pathogenesis of atherosclerosis. We hypothesized that sLOX-1 might be associated with CSFP, and aimed to research the relationship between sLOX-1 and CSFP. Material and methods Forty patients with angiographically proven CSFP and 43 patients with a normal coronary flow pattern (NCFP) were included in this study. Coronary blood flow was measured according to the Thrombolysis In Myocardial Infarction (TIMI) frame count method. sLOX-1 levels were measured in all study subjects. Results Serum levels of sLOX-1 were significantly higher in the CSFP group than the NCFP group (1061.80 ±422.20 ng/ml vs. 500.043 ±282.97 ng/ml, p < 0.001, respectively). Multivariate logistic regression analysis including sLOX-1, MPV, GGT and uric acid levels revealed a significant association between sLOX-1 levels and CSFP (Exp (B)/OR: 1.006, 95% CI: 1.002–1.010, p = 0.001). Conclusions The present study demonstrated that serum sLOX-1 levels were significantly higher in patients with CSFP and there was a strong association between high sLOX-1 levels and CSFP. High serum sLOX-1 levels may have an important role in the pathogenesis of CSFP. Future studies are needed to confirm these results. PMID:26925116

  16. Alpinetin enhances cholesterol efflux and inhibits lipid accumulation in oxidized low-density lipoprotein-loaded human macrophages.

    PubMed

    Jiang, Zhengming; Sang, Haiqiang; Fu, Xin; Liang, Ying; Li, Ling

    2015-01-01

    Alpinetin is a natural flavonoid abundantly present in the ginger family. Here, we investigated the effect of alpinetin on cholesterol efflux and lipid accumulation in oxidized low-density lipoprotein (ox-LDL)-treated THP-1 macrophages and human peripheral blood monocyte-derived macrophages (HMDMs). After exposing THP-1 macrophages to alpinetin, cholesterol efflux was determined by liquid scintillator. The mRNA and protein levels of peroxisome proliferator-activated receptor gamma (PPAR-γ), liver X receptor alpha (LXR-α), ATP-binding cassette transporter A1 (ABCA1), and ABCG1 and scavenger receptor class B member 1 were determined by reverse-transcriptase PCR (RT-PCR) and Western blot analysis, respectively. Alpinetin promoted apolipoprotein A-I- and high-density-lipoprotein-mediated cholesterol efflux and elevated PPAR-γ and LXR-α mRNA and protein expression in a dose-dependent fashion in ox-LDL-treated THP-1 macrophages and HMDMs. Small interfering RNA-mediated silencing of PPAR-γ or LXR-α dose dependently reversed alpinetin-increased cholesterol efflux in THP-1 macrophages, indicating the involvement of PPAR-γ and LXR-α in alpinetin-promoted cholesterol efflux. Alpinetin inhibited ox-LDL-induced lipid accumulation and enhanced the expression of ABCA1 and ABCG1 mRNA and protein, which was reversed by specific knockdown of PPAR-γ or LXR-α. Taken together, our results reveal that alpinetin exhibits positive effects on cholesterol efflux and inhibits ox-LDL-induced lipid accumulation, which might be through PPAR-γ/LXR-α/ABCA1/ABCG1 pathway.

  17. Cell membrane damage is involved in the impaired survival of bone marrow stem cells by oxidized low-density lipoprotein.

    PubMed

    Li, Xin; Xiao, Yuan; Cui, Yuqi; Tan, Tao; Narasimhulu, Chandrakala A; Hao, Hong; Liu, Lingjuan; Zhang, Jia; He, Guanglong; Verfaillie, Catherine M; Lei, Minxiang; Parthasarathy, Sampath; Ma, Jianjie; Zhu, Hua; Liu, Zhenguo

    2014-12-01

    Cell therapy with bone marrow stem cells (BMSCs) remains a viable option for tissue repair and regeneration. A major challenge for cell therapy is the limited cell survival after implantation. This study was to investigate the effect of oxidized low-density lipoprotein (ox-LDL, naturally present in human blood) on BMSC injury and the effect of MG53, a tissue repair protein, for the improvement of stem cell survival. Rat bone marrow multipotent adult progenitor cells (MAPCs) were treated with ox-LDL, which caused significant cell death as reflected by the increased LDH release to the media. Exposure of MAPCs to ox-LDL led to entry of fluorescent dye FM1-43 measured under confocal microscope, suggesting damage to the plasma membrane. Ox-LDL also generated reactive oxygen species (ROS) as measured with electron paramagnetic resonance spectroscopy. While antioxidant N-acetylcysteine completely blocked ROS production from ox-LDL, it failed to prevent ox-LDL-induced cell death. When MAPCs were treated with the recombinant human MG53 protein (rhMG53) ox-LDL induced LDH release and FM1-43 dye entry were significantly reduced. In the presence of rhMG53, the MAPCs showed enhanced cell survival and proliferation. Our data suggest that membrane damage induced by ox-LDL contributed to the impaired survival of MAPCs. rhMG53 treatment protected MAPCs against membrane damage and enhanced their survival which might represent a novel means for improving efficacy for stem cell-based therapy for treatment of diseases, especially in setting of hyperlipidemia.

  18. Oxidized low-density lipoprotein inhibits THP-1-derived macrophage autophagy via TET2 down-regulation.

    PubMed

    Li, Guohua; Peng, Juan; Liu, Yanhui; Li, Xiaohong; Yang, Qin; Li, Yongqing; Tang, Zhihan; Wang, Zuo; Jiang, Zhisheng; Wei, Dangheng

    2015-02-01

    Oxidized low-density lipoprotein (ox-LDL) is an independent risk factor of atherosclerosis. However, the mechanism underlying its pro-atherosclerosis roles has not yet been well explored. DNA demethylation modification, via DNA methyltransferases or ten-eleven-translocation (TET) family, is a crisis epigenetic regulation for various biological and pathological processes. This study aimed to investigate the effects of ox-LDL on macrophage autophagy and its potential epigenetic mechanism. Results showed that after treatment with 0, 10, 20, 40 or 80 mg/L ox-LDL for 24 h, the autophagy markers Beclin 1 and LC3 expression were obviously decreased at protein levels (P < 0.05). The mRNA and protein expression of TET2 was evidently decreased (P < 0.05). After pre-treatment with TET2 siRNA, the mRNA and protein levels of Beclin 1 and LC3 decreased compared with the 80 mg/L treatment group (P < 0.01). The mRNA and protein levels of Beclin 1 and LC3-II were up-regulated (P < 0.05) in the 5-aza-2'-deoxycytidine (a DNA methyltransferase inhibitor) of pretreatment group. Consistent with the Western blot results, cell immunofluorescence showed that the protein concentration of LC3-II decreased in the TET2 siRNA group and increased in the 5-aza-2'-deoxycytidine group. Taken together, these results showed that DNA demethylation modifications regulate ox-LDL-treated THP-1 macrophages autophagy and TET2 might be a novel regulator.

  19. Both poor cardiorespiratory and weak muscle fitness are related to a high concentration of oxidized low-density lipoprotein lipids.

    PubMed

    Kosola, J; Ahotupa, M; Kyröläinen, H; Santtila, M; Vasankari, T

    2012-12-01

    Good physical fitness is associated with favorable serum lipids. Oxidized low-density lipoprotein (ox-LDL) could be even more atherogenic than serum lipids. We studied the association of ox-LDL and serum lipids with physical fitness. Healthy young (mean age 25 years) men (n=846) underwent maximal oxygen uptake (VO(2max)) and muscle fitness index (MFI) tests and completed a leisure-time physical activity (LTPA) questionnaire. Age (ANCOVA1), age+waist circumference+systolic blood pressure+fasting blood glucose+smoking (ANCOVA3) were used as covariates. The groups with the lowest VO(2max), MFI and LTPA had 23%, 16% and 8% higher concentrations of ox-LDL than the groups with the highest VO(2max) (P<0.0001), MFI (P=0.022) and LTPA (P=0.039) groups, respectively. Subjects with poor fitness (low VO(2max) or low MFI) or low LTPA had elevated levels of ox-LDL/high-density lipoprotein (HDL)-cholesterol, total cholesterol, LDL-cholesterol, triglycerides and a low level of HDL-cholesterol (ANCOVA1, in all, P<0.05). Furthermore, low VO(2max) is associated with a high level of ox-LDL/HDL-cholesterol and triglycerides, and with a low level of HDL-cholesterol (ANCOVA3, in all, P<0.05). Also, subjects with low LTPA had a high ratio of ox-LDL/HDL-cholesterol (ANCOVA1, P=0.001). In conclusion, both poor fitness (both low VO(2max) and low MFI) and low LTPA are associated with a higher concentration of ox-LDL lipids and serum lipids, which may indicate a higher risk for atherosclerosis.

  20. Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36-deficient subjects.

    PubMed Central

    Nozaki, S; Kashiwagi, H; Yamashita, S; Nakagawa, T; Kostner, B; Tomiyama, Y; Nakata, A; Ishigami, M; Miyagawa, J; Kameda-Takemura, K

    1995-01-01

    To clarify the physiological roles of CD36 as an oxidized low density lipoprotein (OxLDL) receptor, we analyzed the monocyte-derived macrophages from normal and two CD36-deficient subjects, since we identified the molecular abnormalities (Kashiwagi, H., Y. Tomiyama, Y. Kosugi, M. Shiraga, R. H. Lipsky, Y. Kanayama, Y. Kurata, and Y. Matsuzawa 1994. Blood. 83:3545-3552; and Kashiwagi, H., Y. Tomiyama, S. Honda, S. Kosugi, M. Shiraga, N. Nagao, S. Sekiguchi, Y. Kanayama, Y. Kurata, and Y. Matsuzawa. 1995. J. Clin. Invest. 95:1040-1046). Scatchard analysis of 125I-OxLDL binding showed a linear plot and the maximum binding was lower by approximately 40% in the macrophages from subjects with CD36 deficiency than those from normal controls. Competition studies showed that the uptake of 125I-OxLDL was suppressed by OKM5, an antibody against CD36, by 53% in normal control macrophages, but not in the CD36-deficient macrophages. After incubation with OxLDL for 24 h, cholesteryl ester mass accumulation was reduced by approximately 40% in the macrophages from CD36-deficient subjects than those from normal controls. These results suggest that CD36 is one of the physiological receptors for OxLDL. Since specific binding of OxLDL was only reduced by approximately 40% in spite of the complete deficiency of CD36, several other receptors also may have some role in OxLDL uptake. Further studies will be needed to assess the quantitative role of CD36 in foam cell formation in vivo. Images PMID:7560077

  1. Structure and chromosomal assignment of the human lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) gene.

    PubMed Central

    Aoyama, T; Sawamura, T; Furutani, Y; Matsuoka, R; Yoshida, M C; Fujiwara, H; Masaki, T

    1999-01-01

    We have reported the cDNA cloning of a modified low-density-lipoprotein (LDL) receptor, designated lectin-like oxidized LDL receptor-1 (LOX-1), which is postulated to be involved in endothelial dysfunction and the pathogenesis of atherosclerosis. Here, we determined the organization of the human LOX-1 gene, including the 5'-regulatory region. The 5'-regulatory region contained several potential cis-regulatory elements, such as GATA-2 binding element, c-ets-1 binding element, 12-O-tetradecanoylphorbol 13-acetate-responsive element and shear-stress-responsive elements, which may mediate the endothelium-specific and inducible expression of LOX-1. The major transcription-initiation site was found to be located 29 nucleotides downstream of the TATA box and 61 nucleotides upstream from the translation-initiation codon. The minor initiation site was found to be 5 bp downstream from the major site. Most of the promoter activity of the LOX-1 gene was ascribed to the region (-150 to -90) containing the GC and CAAT boxes. The coding sequence was divided into 6 exons by 5 introns. The first 3 exons corresponded to the different functional domains of the protein (cytoplasmic, transmembrane and neck domains), and the residual 3 exons encoded the carbohydrate-recognition domain similar to the case of other C-type lectin genes. The LOX-1 gene was a single-copy gene and assigned to the p12.3-p13.2 region of chromosome 12. Since the locus for a familial hypertension has been mapped to the overlapping region, LOX-1 might be the gene responsible for the hypertension. PMID:10085242

  2. Oxidized low-density lipoprotein alters the effect of matrix stiffness on the formation of endothelial networks and capillary lumens

    PubMed Central

    2013-01-01

    Abstract Formation of new blood vessels is essential for vascular repair and remodeling, and it is known that biomechanical properties of extracellular matrix play a major role in this process. Our earlier studies have also shown that exposing endothelial cells to oxidized modification of low-density lipoproteins (oxLDL) increases endothelial stiffness and facilitates their ability to form cellular networks, suggesting that it facilitates endothelial angiogenic potential. The goal of this study, therefore, was to test the interrelationship between matrix stiffness and oxLDL in the regulation of angiogenesis. Our results show that, as expected, an increase in matrix stiffness inhibited endothelial network formation and that exposure to oxLDL significantly facilitated this process. We also show, however, that oxLDL-induced facilitation of endothelial networks was observed only in stiff (3 mg/mL) but not in soft (1 mg/mL) collagen gels, resulting in blunting the effect of matrix stiffness. Also unexpectedly, we show that an increase in matrix stiffness results in a significant increase in the number of capillary lumens that are formed by single cells or pairs of cells, suggesting that while endothelial connectivity is impaired, formation of single-cell lumens is facilitated. oxLDL facilitates lumen formation, but this effect is also matrix dependent and is observed only in soft gels and not in stiff gels. Finally, an increase in both matrix stiffness and oxLDL exposure results in changes in capillary morphology, with the formation of larger capillary lumens. Overall, our study suggests that oxLDL plays an important role in formation of new capillaries and their morphology and that this effect is critically dependent on the extracellular environment’s compliance, thereby underlining the importance of the interdependence of these parameters. PMID:24618546

  3. Oxidized low-density lipoprotein alters the effect of matrix stiffness on the formation of endothelial networks and capillary lumens.

    PubMed

    Gundavaram, Madhu S; Shentu, Tzu Pin; Kowalsky, Gregory B; Volkov, Suncica; Schraufnagel, Dean E; Levitan, Irena

    2013-09-01

    Abstract Formation of new blood vessels is essential for vascular repair and remodeling, and it is known that biomechanical properties of extracellular matrix play a major role in this process. Our earlier studies have also shown that exposing endothelial cells to oxidized modification of low-density lipoproteins (oxLDL) increases endothelial stiffness and facilitates their ability to form cellular networks, suggesting that it facilitates endothelial angiogenic potential. The goal of this study, therefore, was to test the interrelationship between matrix stiffness and oxLDL in the regulation of angiogenesis. Our results show that, as expected, an increase in matrix stiffness inhibited endothelial network formation and that exposure to oxLDL significantly facilitated this process. We also show, however, that oxLDL-induced facilitation of endothelial networks was observed only in stiff (3 mg/mL) but not in soft (1 mg/mL) collagen gels, resulting in blunting the effect of matrix stiffness. Also unexpectedly, we show that an increase in matrix stiffness results in a significant increase in the number of capillary lumens that are formed by single cells or pairs of cells, suggesting that while endothelial connectivity is impaired, formation of single-cell lumens is facilitated. oxLDL facilitates lumen formation, but this effect is also matrix dependent and is observed only in soft gels and not in stiff gels. Finally, an increase in both matrix stiffness and oxLDL exposure results in changes in capillary morphology, with the formation of larger capillary lumens. Overall, our study suggests that oxLDL plays an important role in formation of new capillaries and their morphology and that this effect is critically dependent on the extracellular environment's compliance, thereby underlining the importance of the interdependence of these parameters.

  4. Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved[S

    PubMed Central

    Chen, Chao-Hung; Ke, Liang-Yin; Chan, Hua-Chen; Lee, An-Sheng; Lin, Kun-Der; Chu, Chih-Sheng; Lee, Mei-Yueh; Hsiao, Pi-Jung; Hsu, Chin; Chen, Chu-Huang; Shin, Shyi-Jang

    2016-01-01

    Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. “Stimulated by retinoic acid 6” (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor α, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFβ1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells. These L5-induced changes of STRA6 cascades, renal apoptosis, and fibrosis were reversed in kidneys of LOX1−/− mice. LOX1 RNA silencing and inhibitor of c-Jun N-terminal kinase and p38MAPK rescued the suppression of STRA6 cascades and apoptosis and fibrosis in L5-treated renal tubular cells. Furthermore, crbp1 gene transfection reversed downregulation of STRA6 cascades, apoptosis, and fibrosis in L5-treated renal tubular cells. For mimicking STRA6 deficiency, efficient silencing of STRA6 RNA was performed and was found to repress STRA6 cascades and caused apoptosis and fibrosis in L1-treated renal tubular cells. In summary, this study reveals that electronegative L5 can cause kidney apoptosis and fibrosis via the suppression of STRA6 cascades, and implicates that STRA6 signaling may be involved in dyslipidemia-mediated kidney disease. PMID:27256691

  5. Attenuated suppression of the oxidative burst by cells dying in the presence of oxidized low density lipoprotein.

    PubMed

    Namgaladze, Dmitry; Jennewein, Carla; Preiss, Stefan; von Knethen, Andreas; Brüne, Bernhard

    2009-11-01

    Macrophages ingesting apoptotic cells attenuate inflammatory responses, such as reactive oxygen species (ROS) generation. In atherosclerosis, ongoing inflammation and accumulation of apoptotic/necrotic material are observed, suggesting defects of phagocytes in recognizing or responding to dying cells. Modified lipoproteins such as oxidized LDL (oxLDL) are known to promote inflammation and to interfere with apoptotic cell clearance. Here, we studied the impact of cells exposed to oxLDL on their ability to interfere with the oxidative burst in phagocytes. In contrast to apoptotic cells, cells dying in response to or in the presence of oxLDL failed to suppress ROS generation despite efficiently being taken up by phagocytes. In addition, apoptotic cells, but not oxLDL-treated cells, inhibited phosphorylation of extracellular signal-regulated kinase, which is important for NADPH oxidase activation. oxLDL treatment did not interfere with activation of the antiinflammatory transcriptional regulator peroxisome proliferator-activated receptor gamma by apoptotic cells. Moreover, cells exposed to oxLDL failed to suppress lipopolysaccharide- induced proinflammatory cytokine expression, whereas apoptotic cells attenuated these phagocyte responses. Thus, the presence of oxLDL during cell death impaired the ability of apoptotic cells to act antiinflammatory with regard to oxidative burst inhibition and cytokine expression in phagocytes.

  6. Lectin-like Oxidized Low-Density Lipoprotein (LDL) Receptor (LOX-1): A Chameleon Receptor for Oxidized LDL.

    PubMed

    Zeya, Bushra; Arjuman, Albina; Chandra, Nimai Chand

    2016-08-16

    LOX-1, one of the main receptors for oxLDL, is found mainly on the surface of endothelial cells. It is a multifacet 52 kDa type II transmembrane protein that structurally belongs to the C-type lectin family. It exists with short intracellular N-terminal and long extracellular C-terminal hydrophilic domains separated by a hydrophobic domain of 26 amino acids. LOX-1 acts like a bifunctional receptor either showing pro-atherogenicity by activating the NFκB-mediated down signaling cascade for gene activation of pro-inflammatory molecules or playing an atheroprotective agent by receptor-mediated uptake of oxLDL in the presence of an anti-inflammatory molecule like IL-10. Mildly, moderately, and highly oxidized LDL show their characteristic features upon LOX-1 activation and its ligand binding indenture. The polymorphic LOX-1 genes are intensively associated with increased susceptibility to myocardial diseases. The splicing variant LOX IN dimerizes with the native form of LOX-1 and protects cells from damage by oxidized LDL. In the developing field of regenerating medicine, LOX-1 is a potential target for therapeutic intervention.

  7. Lectin-like Oxidized Low-Density Lipoprotein (LDL) Receptor (LOX-1): A Chameleon Receptor for Oxidized LDL.

    PubMed

    Zeya, Bushra; Arjuman, Albina; Chandra, Nimai Chand

    2016-08-16

    LOX-1, one of the main receptors for oxLDL, is found mainly on the surface of endothelial cells. It is a multifacet 52 kDa type II transmembrane protein that structurally belongs to the C-type lectin family. It exists with short intracellular N-terminal and long extracellular C-terminal hydrophilic domains separated by a hydrophobic domain of 26 amino acids. LOX-1 acts like a bifunctional receptor either showing pro-atherogenicity by activating the NFκB-mediated down signaling cascade for gene activation of pro-inflammatory molecules or playing an atheroprotective agent by receptor-mediated uptake of oxLDL in the presence of an anti-inflammatory molecule like IL-10. Mildly, moderately, and highly oxidized LDL show their characteristic features upon LOX-1 activation and its ligand binding indenture. The polymorphic LOX-1 genes are intensively associated with increased susceptibility to myocardial diseases. The splicing variant LOX IN dimerizes with the native form of LOX-1 and protects cells from damage by oxidized LDL. In the developing field of regenerating medicine, LOX-1 is a potential target for therapeutic intervention. PMID:27419271

  8. Pericoronary Adipose Tissue as Storage and Supply Site for Oxidized Low-Density Lipoprotein in Human Coronary Plaques

    PubMed Central

    Uchida, Yasumi; Uchida, Yasuto; Shimoyama, Ei; Hiruta, Nobuyuki; Kishimoto, Toshihiko; Watanabe, Soichiro

    2016-01-01

    Objectives It is generally believed that low-density lipoprotein enters the vascular wall from its lumen and oxidized (oxLDL), after which it plays an important role in atherosclerosis. Because voluminous epicardial adipose tissue is a risk factor for coronary events, there is a possibility that the pericoronary adipose tissue (PCAT), which is a part of epicardial adipose tissue, acts as a risk factor by supplying oxLDL to the coronary arterial wall. The present study was performed whether PCAT stores and supplies oxLDL to the coronary wall. Methods Localization of oxLDL in PCAT and its relation to plaque morphology were examined by immunohistochemical techniques in 27 epicardial coronary arteries excised from 9 human autopsy cases. Results OxLDL deposited in all PCAT of the studied cases. The percent (%) incidence of oxLDL in the intima of 25 normal segment, 19 white plaques, 15 yellow plaques without necrotic core (NC) and 10 yellow plaques with NC, was 32, 84, 93 (p<0.05 vs normal segments and yellow plaques with NC), and 30, respectively. OxLDL deposited either in dotted or diffuse pattern. Double immunohistochemical staining revealed that the dotted oxLDL was that contained in CD68(+)-macrophages. The oxLDL-containing macrophages were observed in the interstitial space but not inside of the vasa vasorum, and they traversed PCAT, adventitia, external and internal elastic laminae, suggesting their migration towards the intima. Diffuse oxLDL deposits were observed in 17 preparations, the majority of which were co-localized with the vasa vasorum in outer or in both inner and outer halves of intima, and rarely in the inner half alone. Conclusions The results suggested that PCAT is a supply source of oxLDL to coronary intima and acts as a risk factor for coronary events, that oxLDL increasingly deposits in the intima with plaque growth and decreases after plaque maturation, and therefore molecular therapies targeting the PCAT before plaque growth could be effective

  9. Oxidized Low-Density Lipoprotein and the Incidence of Proliferative Diabetic Retinopathy and Clinically Significant Macular Edema Determined From Fundus Photographs

    PubMed Central

    Klein, Ronald; Myers, Chelsea E.; Lee, Kristine E.; Paterson, Andrew D.; Cruickshanks, Karen J.; Tsai, Michael Y.; Gangnon, Ronald E.; Klein, Barbara E. K.

    2015-01-01

    IMPORTANCE Studies have shown oxidized low-density lipoprotein to be associated with the incidence of proliferative retinopathy and other complications of type 1 diabetes mellitus. Because low-risk interventions are available to modify oxidized low-density lipoprotein, it is important to examine the relationships between this factor and the incidence of proliferative retinopathy and of macular edema, 2 important causes of visual impairment in people with type 1 diabetes. OBJECTIVE To determine the association of oxidized low-density lipoprotein with the worsening of diabetic retinopathy and the incidence of proliferative retinopathy and of macular edema. DESIGN, SETTING, AND PARTICIPANTS Of 996 participants with type 1 diabetes in the Wisconsin Epidemiologic Study of Diabetic Retinopathy, 730 were examined up to 4 times (1990-1992, 1994-1996, 2005-2007, and 2012-2014) over 24 years and had assays of oxidized low-density lipoprotein and fundus photographs gradable for diabetic retinopathy and macular edema. Analyses started July 2014 and ended February 2015. MAIN OUTCOMES AND MEASURES Worsening of diabetic retinopathy, incidence of proliferative diabetic retinopathy, and incidence of macular edema as assessed via grading of color stereo film fundus photographs. The levels of oxidized low-density lipoprotein collected from serum samples at the time of each examination were measured in 2013 and 2014 from frozen serum. RESULTS The cohort at baseline had a mean (SD) level of oxidized low-density lipoprotein of 30.0 (8.5) U/L. While adjusting for duration of diabetes, glycated hemoglobin A1c level, and other factors, we found that neither the level of oxidized low-density lipoprotein at the beginning of a period nor the change in it over a certain period was associated with the incidence of proliferative diabetic retinopathy (hazard ratio [HR], 1.11 [95% CI, 0.91-1.35], P = .30; odds ratio [OR], 1.77 [95% CI, 0.99-3.17], P = .06), the incidence of macular edema (HR, 1

  10. Fermentation with Aspergillus awamori enhanced contents of amino nitrogen and total phenolics as well as the low-density lipoprotein oxidation inhibitory activity of black soybeans.

    PubMed

    Chen, Yu-Fei; Lee, Shiow-Ling; Chou, Cheng-Chun

    2011-04-27

    A solid fermentation was performed on black soybeans with Aspergillus awamori. The effects of fermentation on the contents of total phenolics and amino nitrogen and on the inhibitory effect on low-density lipoprotein (LDL) oxidation of black soybeans were examined. Results revealed that fermentation significantly enhanced the LDL oxidation inhibitory activity and total phenolics and amino nitrogen contents of black soybeans. The increased content of amino nitrogen was closely related to the enhanced LDL oxidation inhibitory activity of fermented black soybeans and its water extract. Fermentation temperature and length affected the LDL oxidation inhibitory effect exerted by the prepared fermented black soybeans. The A. awamori-fermented black soybean prepared at 30 °C for 3 days exhibited the highest inhibitory effect on LDL oxidation. The bioactive principles related to the inhibitory effect on LDL oxidation in black soybeans, regardless of fermentation, could be most efficiently extracted with water rather than 80% methanol or 80% ethanol.

  11. Serum Lectin-Like Oxidized-Low Density Lipoprotein Receptor-1 and Adiponectin Levels Are Associated With Coronary Artery Disease Accompanied With Metabolic Syndrome

    PubMed Central

    Md Sayed, Ali Sheikh; Zhao, Zhenyu; Guo, Lanyan; Li, Fei; Deng, Xu; Deng, Hai; Xia, Ke; Yang, Tianlun

    2014-01-01

    Background: Coronary artery disease (CAD) is a major public health problem for developed and developing countries and is the single leading cause of death worldwide. Objectives: There is very few evidence regarding changes of both serum Lectin-like oxidized-low density lipoprotein receptor-1 (LOX-1) and adiponectin in patients with CAD accompanied with metabolic syndrome (MS). Here we aimed to evaluate serum levels of LOX-1 and adiponectin in patients with CAD accompanied with MS. Patients and Methods: Thirty patients with coronary artery disease without metabolic syndrome, 30 patients with coronary artery disease and metabolic syndrome, 30 ones with metabolic syndrome and 30 healthy subjects were enrolled. For all subjects, a questionnaire was filled to collect data, and peripheral blood samples were collected aseptically from the antecubital vein to measure serum Lectin-like oxidized-low density lipoprotein receptor-1 and adiponectin levels by enzyme-linked immunosorbent assay. Results: Serum LOX-1 level was highest in CAD + MS group; the difference between control and disease groups was statistically significant (P < 0.001). Adiponectin level had the lowest value in CAD + MS group; the difference between control and disease groups was statistically significant (P < 0.05). No significant differences were observed in serum Lectin-like oxidized-low density lipoprotein receptor-1and adiponectin in patients with different ages and gender. Serum LOX-1 level was changed negatively and linearly (R2 = 0.721) correlated with adiponectin level in different groups. Conclusions: Patient with CAD and MS had higher risk than those with only CAD because of lipid and glucose metabolism abnormalities. Combination measurements of serum LOX-1 and adiponectin levels may be helpful to evaluate the severity of CAD together with MS. PMID:25389471

  12. The influence of medium components on Cu(2+)-dependent oxidation of low-density lipoproteins and its sensitivity to superoxide dismutase.

    PubMed

    Thomas, C E

    1992-09-22

    The extent of in vitro Cu(2+)-dependent oxidation of low-density lipoproteins (LDL) has been reported to vary widely depending upon reaction conditions. In this study, the effect of proteins and amino acids on Cu(2+)-induced LDL oxidation was examined. Treatment of LDL with 5 microM CuSO4 for 18 h in either phosphate-buffered saline (PBS) or Ham's F-10 medium resulted in extensive oxidation as determined by the content of thiobarbituric acid reactive substances (TBARS) and by increased lipoprotein electronegativity. In PBS, oxidation was entirely blocked by histidine and the tripeptide, gly-his-lys (GHK). Oxidation was also prevented by bovine serum albumin, but superoxide dismutase (SOD) provided only 20% protection. Both proteins bound similar amounts of Cu2+, but albumin appeared to be a more effective peroxyl radical trap as evidenced by its ability to prevent LDL oxidation induced by 2,2'-azo-bis(2-amidinopropane hydrochloride). In F-10 medium, SOD had marked inhibitory effects, in contrast to PBS. The addition of disulfides to PBS markedly enhanced the ability of SOD to inhibit oxidation. These results indicate that medium components which affect Cu2+ availability influence LDL oxidation and suggest that albumin is ideally suited as a plasma antioxidant to prevent oxidative modification of LDL. Furthermore, in certain instances, the inhibitory effects of SOD may be attributable to effects such as Cu2+ binding rather than dismutation of superoxide. PMID:1390878

  13. Investigation of serum oxidized low-density lipoprotein IgG levels in patients with angiographically defined coronary artery disease.

    PubMed

    Moohebati, Mohsen; Kabirirad, Vahid; Ghayour-Mobarhan, Majid; Esmaily, Habibollah; Tavallaie, Shima; Akhavan Rezayat, Amir; Pourghadamyari, Hossein; Sahebkar, Amirhossein

    2014-01-01

    It has been suggested that antioxidized low-density lipoprotein (anti-oxLDL) antibodies play a role in the pathogenesis of atherosclerosis. The aim of this study was to measure serum ox-LDL IgG levels in 31 patients with angiographically defined coronary artery disease (CAD) (≥50% stenosis in at least one major coronary artery; CAD(+) group) and compare these levels with those of 32 subjects with <50% coronary stenosis (CAD(-) group) and 24 healthy age- and sex-matched controls using ELISA. We did not find any significant difference between CAD(+), CAD(-), and control groups in regard to oxLDL IgG levels (P = 0.83). Serum oxLDL IgG levels did not differ between 1VD (one vessel disease), 2VD (2 vessels disease), and 3VD (3 vessels disease) subgroups of CAD(+) patients (P = 0.20). Serum anti-oxLDL titers were only significantly correlated with LDL-C in the CAD(+) group (P < 0.05) and waist and hip circumference (P < 0.05 and P < 0.01, resp.) in the CAD(-) group. In stepwise regression analysis, none of the conventional cardiovascular risk factors was associated with serum ox-LDL IgG levels. The present results suggest that serum levels of ox-LDL IgG are neither associated with the presence and severity of CAD nor with the conventional cardiovascular risk factors.

  14. Effects of a 12-week healthy-life exercise program on oxidized low-density lipoprotein cholesterol and carotid intima-media thickness in obese elderly women.

    PubMed

    Park, Jong-Hwan; Park, Hyuntae; Lim, Seung-Taek; Park, Jin-Kee

    2015-05-01

    [Purpose] This study examined the effects of a 12-week exercise program on plasma level of oxidized low-density lipoprotein cholesterol in obese elderly women, who are at increased risk of heart disease morbidity. [Subjects and Methods] Twenty participants were assigned into either a control (n = 10) or a supervised exercise program (n = 10) group. The 12-week exercise intervention was performed 3 days per week and involved combined aerobic exercise, resistance exercise, and traditional Korean dance. [Results] Two-factor analysis of variance revealed significant group × time interactions for body mass, diastolic blood pressure, appendicular muscle mass. For high-density lipoprotein cholesterol, oxidized low-density lipoprotein cholesterol, and the ratio of oxidized low-/high-density lipoprotein cholesterol, two-factor analysis of variance revealed significant interactions (group × time), indicating responses differed significantly between the control and exercise groups after 12 weeks. [Conclusion] A 12-week low- to moderate-intensity exercise program appears to be beneficial for obese elderly women by improving risk factors for cardiovascular disease.

  15. Behavior of the thermal diffusivity of native and oxidized human low-density lipoprotein solutions studied by the Z-scan technique

    NASA Astrophysics Data System (ADS)

    Santos, Priscila R.; Genaro-Mattos, Thiago C.; Monteiro, Andrea M.; Miyamoto, Sayuri; Figueiredo Neto, Antonio M.

    2012-10-01

    Modifications in low-density lipoprotein (LDL) have emerged as a major pathogenic factor of atherosclerosis, which is the main cause of morbidity and mortality in the western world. Measurements of the heat diffusivity of human LDL solutions in their native and in vitro oxidized states are presented by using the Z-Scan (ZS) technique. Other complementary techniques were used to obtain the physical parameters necessary to interpret the optical results, e.g., pycnometry, refractometry, calorimetry, and spectrophotometry, and to understand the oxidation phase of LDL particles. To determine the sample's thermal diffusivity using the thermal lens model, an iterative one-parameter fitting method is proposed which takes into account several characteristic ZS time-dependent and the position-dependent transmittance measurements. Results show that the thermal diffusivity increases as a function of the LDL oxidation degree, which can be explained by the increase of the hydroperoxides production due to the oxidation process. The oxidation products go from one LDL to another, disseminating the oxidation process and caring the heat across the sample. This phenomenon leads to a quick thermal homogenization of the sample, avoiding the formation of the thermal lens in highly oxidized LDL solutions.

  16. Protective Effect of Antioxidant Extracts from Grey Oyster Mushroom, Pleurotus pulmonarius (Agaricomycetes), Against Human Low-Density Lipoprotein Oxidation and Aortic Endothelial Cell Damage.

    PubMed

    Abidin, Mohamad Hamdi Zainal; Abdullah, Noorlidah; Abidin, Nurhayati Zainal

    2016-01-01

    This study evaluated the in vitro antioxidant capacities of extracts from Pleurotus pulmonarius via Folin-Ciocalteu, 1,1-diphenyl-2-picrylhydrazyl free radical scavenging, metal chelating, cupric ion reducing antioxidant capacity, and lipid peroxidation inhibition assays. Extract compositions were determined by phenol-sulfuric acid; Coomassie Plus (Bradford) protein; Spectroquant zinc, copper, and manganese test assays; and liquid chromatography-tandem mass spectrometry (LC/MS/MS) and gas chromatography-mass spectrometry (GC/MS). Methanol-dichloromethane extract, water fraction, hot water, aqueous extract and hexane fraction exhibited the most potent extracts in the antioxidant activities. LC/MS/MS and GC/MS showed that the extracts contained ergothioneine, ergosterol, flavonoid, and phenolic compounds. The selected potent extracts were evaluated for their inhibitory effect against oxidation of human low-density lipoproteins and protective effects against hydrogen peroxide-induced cytotoxic injury in human aortic endothelial cells. The crude aqueous extract was deemed most potent for the prevention of human low-density lipoprotein oxidation and endothelial membrane damage. Ergothioneine might be the compound responsible for the activities, as supported by previous reports. Thus, P. pulmonarius may be a valuable antioxidant ingredient in functional foods or nutraceuticals. PMID:27279533

  17. Purification, crystallization and preliminary X-ray analysis of the ligand-binding domain of human lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1)

    SciTech Connect

    Ishigaki, Tomoko; Ohki, Izuru; Oyama, Takuji; Machida, Sachiko; Morikawa, Kousuke; Tate, Shin-ichi

    2005-05-01

    Two different fragments of the ligand-binding domain of LOX-1, the major receptor for oxidized low-density lipoprotein (LDL) on endothelial cells, have been crystallized in different forms. Two different fragments of the ligand-binding domain of LOX-1, the major receptor for oxidized low-density lipoprotein (LDL) on endothelial cells, have been crystallized in different forms. One crystal form contains the disulfide-linked dimer, which is the form of the molecule present on the cell surface; the other contains a monomeric form of the receptor that lacks the cysteine residue necessary to form disulfide-linked homodimers. The crystal of the monomeric ligand-binding domain belongs to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 56.79, b = 67.57, c = 79.02 Å. The crystal of the dimeric form belongs to space group C2, with unit-cell parameters a = 70.86, b = 49.56, c = 76.73 Å, β = 98.59°. Data for the dimeric form of the LOX-1 ligand-binding domain have been collected to 2.4 Å. For the monomeric form of the ligand-binding domain, native, heavy-atom derivative and SeMet-derivative crystals have been obtained; their diffraction data have been measured to 3.0, 2.4 and 1.8 Å resolution, respectively.

  18. Oxidized or acetylated low density lipoproteins are rapidly cleared by the liver in mice with disruption of the scavenger receptor class A type I/II gene.

    PubMed Central

    Ling, W; Lougheed, M; Suzuki, H; Buchan, A; Kodama, T; Steinbrecher, U P

    1997-01-01

    Oxidized low density lipoprotein (LDL) and acetyl LDL are recognized by the scavenger receptor class A type I/II (SR-AI/II) on macrophages and liver endothelial cells. Several investigators have suggested that there are additional receptors specific for oxidized LDL, but characterization of these alternate receptors for oxidized LDL and evaluation of their quantitative importance in uptake of oxidized LDL has been difficult because of overlapping ligand specificity with SR-AI/II. The purpose of this study was to determine the importance of SR-AI/II in the removal of modified LDL from the bloodstream in vivo. The clearance rate of oxidized LDL from plasma in normal mice was very rapid, and > 90% of injected dose was removed from the blood within 5 min. Clearance rates of oxidized LDL were equally high in SR-AI/II knockout mice, indicating that this receptor is not required for removal of oxidized LDL from plasma. Surprisingly, there was no difference in the clearance rate of acetyl LDL in wild-type and SR-AI/II knockout animals. The plasma clearance of radioiodinated acetyl LDL was almost fully blocked by a 50-fold excess of unlabeled acetyl LDL, but the latter only inhibited oxidized LDL clearance by approximately 5%. Both modified LDLs were cleared mostly by the liver, and there was no difference in the tissue distribution of modified LDL in control and knockout mice. Studies in isolated nonparenchymal liver cells showed that Kupffer cells accounted for most of the uptake of oxidized LDL. Extensively oxidized LDL and LDL modified by exposure to fatty acid peroxidation products were efficient competitors for the uptake of labeled oxidized LDL by SR-AI/II-deficient Kupffer cells, while acetyl LDL and malondialdehyde-modified LDL were relatively poor competitors. PMID:9218499

  19. Differential regulation of acid sphingomyelinase in macrophages stimulated with oxidized low-density lipoprotein (LDL) and oxidized LDL immune complexes: role in phagocytosis and cytokine release.

    PubMed

    Truman, Jean-Philip; Al Gadban, Mohammed M; Smith, Kent J; Jenkins, Russell W; Mayroo, Nalini; Virella, Gabriel; Lopes-Virella, Maria F; Bielawska, Alicja; Hannun, Yusuf A; Hammad, Samar M

    2012-05-01

    Oxidized low-density lipoprotein (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) contribute to the formation of lipid-laden macrophages (foam cells). Fcγ receptors mediate uptake of oxLDL-IC, whereas scavenger receptors internalize oxLDL. We have previously reported that oxLDL-IC, but not free oxLDL, activate macrophages and prolong their survival. Sphingomyelin is a major constituent of cell membranes and lipoprotein particles and acid sphingomyelinase (ASMase) hydrolyses sphingomyelin to generate the bioactive lipid ceramide. ASMase exists in two forms: lysosomal (L-ASMase) and secretory (S-ASMase). In this study we examined whether oxLDL and oxLDL-IC regulate ASMase differently, and whether ASMase mediates monocyte/macrophage activation and cytokine release. The oxLDL-IC, but not oxLDL, induced early and consistent release of catalytically active S-ASMase. The oxLDL-IC also consistently stimulated L-ASMase activity, whereas oxLDL induced a rapid transient increase in L-ASMase activity before it steadily declined below baseline. Prolonged exposure to oxLDL increased L-ASMase activity; however, activity remained significantly lower than that induced by oxLDL-IC. Further studies were aimed at defining the function of the activated ASMase. In response to oxLDL-IC, heat-shock protein 70B' (HSP70B') was up-regulated and localized with redistributed ASMase in the endosomal compartment outside the lysosome. Treatment with oxLDL-IC induced the formation and release of HSP70-containing and IL-1β-containing exosomes via an ASMase-dependent mechanism. Taken together, the results suggest that oxLDL and oxLDL-IC differentially regulate ASMase activity, and the pro-inflammatory responses to oxLDL-IC are mediated by prolonged activation of ASMase. These findings may contribute to increased understanding of mechanisms mediating macrophage involvement in atherosclerosis.

  20. Oxidized Low-Density Lipoprotein-β2-Glycoprotein I Complex But Not Free Oxidized LDL Is Associated With the Presence and Severity of Coronary Artery Disease.

    PubMed

    Bliden, Kevin P; Chaudhary, Rahul; Lopez, Luis R; Damrongwatanasuk, Rongras; Guyer, Kirk; Gesheff, Martin G; Franzese, Christopher J; Kaza, Himabindu; Tantry, Udaya S; Gurbel, Paul A

    2016-09-01

    Oxidized low-density lipoprotein (oxLDL) and β2-glycoprotein I (β2GPI) have been identified in human atherosclerotic lesions and when complexed have been implicated as a pro-atherothrombotic antigen. We examined the association of free oxLDL and oxLDL-β2GPI complex in patients with coronary artery disease who underwent elective cardiac catheterization. Serum was collected from patients with suspected coronary artery disease immediately before elective cardiac catheterization who were either treated (n = 385) or not treated (n = 150) with statins and from healthy volunteers (n = 134). OxLDL and oxLDL-β2GPI complex levels were determined by enzyme-linked immunosorbent assay. Disease severity was defined angiographically as none-minimal (<20%), moderate (20% to 75%), and severe (>75%) luminal diameter obstruction of any major coronary vessel. Both oxLDL and oxLDL-β2GPI complex were lower in patients on statins (p <0.001). In statin-naive patients, oxLDL-β2GPI complex, but not free oxLDL, was associated with severe coronary artery disease (p = 0.036). However, no association was observed in patients on statins. LDL4 and triglycerides increased with oxLDL-β2GPI complex quartiles (p = 0.001). OxLDL-β2GPI complex (>0.32 U/ml) was predictive of severe atherosclerosis by receiver-operating characteristic curve analysis in statin-naive patients (area under the curve 0.66, p = 0.002). In conclusion, oxLDL-β2GPI appears more predictive of coronary artery disease severity than oxLDL alone in statin-naive patients.

  1. Inhibitory effect of three C-glycosylflavonoids from Cymbopogon citratus (Lemongrass) on human low density lipoprotein oxidation.

    PubMed

    Orrego, Roxana; Leiva, Elba; Cheel, José

    2009-09-30

    This study assessed the inhibitory effect of three C-glycosylflavonoids from Cymbopogon citratus leaves--isoorientin (1), swertiajaponin (2) and isoorientin 2"-Orhamnoside (3)--on human LDL oxidation. Isolated LDL was incubated with compounds 1-3 and the kinetics of lipid peroxidation were assessed by conjugated diene and malondialdehyde-thiobarbituric acid reactive substances (MDA-TBARS) formation after addition of copper ions. Significant differences (p < 0.05) between the lag time phase of the control and the lag time phase in the presence of the compounds 1 (0.25 microM) and 2 (0.50 microM) were observed. After five hours of incubation all three compounds showed a significant inhibitory effect on MDA-TBARS formation with respect to the control. After six hours of incubation only compound 1 kept a remarkable antioxidant effect. This study demonstrates that isoorientin (1) is an effective inhibitor of in vitro LDL oxidation. As oxidative damage to LDL is a key event in the formation of atherosclerotic lesions, the use of this natural antioxidant may be beneficial to prevent or attenuate atherosclerosis.

  2. Lysophosphatidylcholine, oxidized low-density lipoprotein and cardiovascular disease in Korean hemodialysis patients: analysis at 5 years of follow-up.

    PubMed

    Lee, Young-Ki; Lee, Dong Hun; Kim, Jin Kyung; Park, Min-Jeong; Yan, Ji-Jing; Song, Dong-Keun; Vaziri, Nosratola D; Noh, Jung-Woo

    2013-02-01

    Although oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (LPC) have been proposed as important mediators of the atherosclerosis, the long-term contribution to the risk of cardiovascular disease (CVD) in hemodialysis patients has not been evaluated. This study investigated the relation between oxidized LDL and LPC levels with long term risk of CVD. Plasma oxidized LDL and LPC levels were determined in 69 Korean hemodialysis patients as a prospective observational study for 5 yr. During the observation period, 18 cardiovascular events (26.1%) occurred including 6 deaths among the hemodialysis patients. The low LPC level group (≤ 254 µM/L, median value) had much more increased risk of CVD compared to the high LPC level group (> 254 µM/L) (P = 0.01). However, serum levels of oxidized LDL were not significantly different between groups with and without CVD. In adjusted Cox analysis, previous CVD, (hazard ratio [HR], 5.68; 95% confidence interval [CI], 1.94-16.63, P = 0.002) and low LPC level (HR, 3.45; 95% CI, 1.04-11.42, P = 0.04) were significant independent risk factors for development of CVD. It is suggested that low LPC, but not oxidized LDL, is associated with increased risk of CVD among a group of Korean hemodialysis patients.

  3. Development and application of a nonradioactive binding assay of oxidized low-density lipoprotein to macrophage scavenger receptors

    PubMed Central

    Montano, Erica N.; Boullier, Agnès; Almazan, Felicidad; Binder, Christoph J.; Witztum, Joseph L.; Hartvigsen, Karsten

    2013-01-01

    Macrophages play a key role in atherogenesis in part through excessive uptake of oxidized LDL (OxLDL) via scavenger receptors. Binding of OxLDL to macrophages has traditionally been assessed using radiolabeled OxLDL. To allow more efficient and convenient measurements, we developed a nonradioactive binding assay in which biotinylated OxLDL (Bt-OxLDL) is added to macrophages in 96-well microtiter culture plates under various conditions and the extent of binding is determined using solid phase chemiluminescent immunoassay techniques. As examples, we show that Bt-OxLDL displayed high and saturable binding to macrophages in contrast to Bt-LDL, which showed very low binding. In competition assays, unlabeled OxLDL and the anti-OxLDL monoclonal antibody E06 inhibited Bt-OxLDL binding to macrophages in a dose-dependent manner. Specific binding of Bt-OxLDL to ApoE/SR-A/CD36 triple knockout macrophages was reduced by 80% as compared with binding to macrophages from ApoE knockout mice. Binding of Bt-OxLDL to CD36 transfected COS-7 cells showed enhanced saturable binding compared with mock-transfected cells. This assay avoids the use of radioactivity and uses small amounts of materials. It can be used to study binding of OxLDL to macrophages and factors that influence this binding. The techniques described should be readily adaptable to study of other ligands, receptors, and cell types. PMID:23997238

  4. Oxidized wax as compatibilizer in linear low-density polyethylene-clay nanocomposites: x-ray diffraction and dynamic mechanical analysis.

    PubMed

    Geethamma, V G; Luyt, Adriaan S

    2008-04-01

    Oxidized paraffin wax was used as a compatibilizer in composites of linear low-density polyethylene and layered nano silicate clays. X-ray diffraction analyses were carried out to investigate the crystalline morphology of five types of clays, oxidized wax, and their composites with LLDPE. The composites exhibited different X-ray diffraction and dynamic mechanical behaviour in the presence of different clays. Generally, the composites retained the partially crystalline behaviour of LLDPE, and no exfoliation was observed. Increased amount of wax did not change the morphology in most cases. The incorporation of clay resulted in an observable increase in the storage modulus of LLDPE. These values also increased with the addition of oxidized wax for most of the composites. The loss modulus increased with the amount of clay, irrespective of its nature. In most cases these values also increased with the incorporation of wax. The composites with 10% clay and 10% oxidized wax showed the highest storage and loss moduli, irrespective of the nature of the clay. The tan delta values did not change considerably with the addition of clay or wax.

  5. Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor.

    PubMed Central

    Yoshida, H; Kondratenko, N; Green, S; Steinberg, D; Quehenberger, O

    1998-01-01

    A new receptor for oxidized low-density lipoprotein (LDL), lectin-like oxidized LDL receptor-1 (LOX-1), has recently been cloned from bovine endothelial cells and human lung. A limited tissue-distribution study suggested that the protein was mainly produced by the vascular endothelium. In the present study we demonstrate that LOX-1 is also expressed in macrophages, where it may function as a scavenger receptor. LOX-1 was not detected in undifferentiated THP-1 cells or in freshly isolated human blood monocytes. However, mature human monocyte-derived macrophages and differentiated THP-1 cells showed high levels of LOX-1 transcripts. Consistent with these results, immunofluorescence staining and FACS analysis demonstrated that LOX-1 protein is expressed on the plasma membrane of macrophages. Western-blot analysis of membranes from macrophages (but not those from monocytes) identified a single band, with an apparent molecular mass of about 40 kDa, that displayed oxidized LDL-binding activity. These results suggest that differentiation induces the expression of LOX-1 in macrophages, where it may play a role as a scavenger receptor and/or a receptor for oxidized LDL. PMID:9693095

  6. Antioxidative Effects and Inhibition of Human Low Density Lipoprotein Oxidation In Vitro of Polyphenolic Compounds in Flammulina velutipes (Golden Needle Mushroom)

    PubMed Central

    Rahman, Mohammad Azizur; Abdullah, Noorlidah; Aminudin, Norhaniza

    2015-01-01

    Dietary polyphenolic compounds mediate polynomial actions in guarding against multiple diseases. Atherosclerosis is an oxidative stress driven pathophysiological complication where free radical induced oxidative modification of low density lipoprotein (LDL) plays the ground breaking role. Mushrooms have been highly regarded for possessing an antioxidant arsenal. Polyphenolic compounds present in dietary mushrooms seem pertinent in withstanding LDL oxidation en route to controlling atherosclerosis. In this study, the antioxidative effect of five solvent fractions consisting of methanol : dichloromethane (M : DCM), hexane (HEX), dichloromethane (DCM), ethyl acetate (EA), and aqueous residue (AQ) of Flammulina velutipes was evaluated. M : DCM fraction showed the most potent 2,2-diphenyl-1-picrylhydrazyl radical scavenging effect with IC50 of 0.86 mg/mL and total phenolic content of 56.36 gallic acid equivalent/g fraction. In LDL oxidation inhibitory tests, M : DCM fraction at 1 µg/mL concentration mostly lengthened the lag time (125 mins) of conjugated diene formation and inhibited the formation of thiobarbituric acid reactive substances (48.71%, at 1 mg/mL concentration). LC-MS/MS analyses of M : DCM fraction identified the presence of polyphenolic substances protocatechuic acid, p-coumaric, and ellagic acid. These chain-breaking polyphenolics might impart the antioxidative effects of F. velutipes. Thus, mushroom-based dietary polyphenolic compounds might be implicated in slowing down the progression of atherosclerosis. PMID:26180589

  7. Effect of a low-density polyethylene film containing butylated hydroxytoluene on lipid oxidation and protein quality of Sierra fish (Scomberomorus sierra) muscle during frozen storage.

    PubMed

    Torres-Arreola, Wilfrido; Soto-Valdez, Herlinda; Peralta, Elizabeth; Cardenas-López, José Luis; Ezquerra-Brauer, Josafat Marina

    2007-07-25

    Fresh sierra fish (Scomberomorus sierra) fillets were packed in low-density polyethylene films with butylated hydroxytoluene (BHT-LDPE) added. Fillets packed in LDPE with no BHT were used as controls (LDPE). The packed fillets were stored at -25 degrees C for 120 days in which the film released 66.5% of the antioxidant. The influence of the antioxidant on lipid and protein quality, lipid oxidation, muscle structure changes, and shear-force resistance was recorded. As compared to LDPE films, fillets packed in BHT-LDPE films showed lower lipid oxidation, thiobarbituric acid values (4.20 +/- 0.52 vs 11.95 +/- 1.06 mg malonaldehyde/kg), peroxide values (7.20 +/- 1.38 vs 15.15 +/- 1.48 meq/kg), and free fatty acids (7.98 +/- 0.43 vs 11.83 +/- 1.26% of oleic acid). Fillets packed in BHT-LDPE films showed less tissue damage and lost less firmness than fillets packed in LDPE. A significant relationship between lipid oxidation and texture was detected (R2 adjusted, 0.70-0.73). BHT-LDPE films may be used not only to prevent lipid oxidation but also to minimize protein damage to prolong the shelf life of sierra fish.

  8. Expression of lectin-like oxidized low density lipoprotein receptor-1 in human and murine macrophages: upregulated expression by TNF-alpha.

    PubMed

    Moriwaki, H; Kume, N; Kataoka, H; Murase, T; Nishi, E; Sawamura, T; Masaki, T; Kita, T

    1998-11-27

    Uptake of oxidized low density lipoprotein (Ox-LDL) and subsequent foam cell transformation have been implicated in early atherogenesis. Although multiple molecules, including class A and B scavenger receptors, have been identified as Ox-LDL receptors, additional receptors may also be involved in this process. Here, we provide evidence that lectin-like Ox-LDL receptor-1 (LOX-1), a novel Ox-LDL receptor initially identified in vascular endothelial cells, is also expressed in macrophages in humans and mice. Expression of LOX-1 can be induced after macrophage-like differentiation in vitro in human peripheral blood monocytes and the related cell line THP-1 cells. Furthermore, LOX-1 expression can also be detected in resident peritoneal macrophages, and can be upregulated by an inflammatory cytokine TNF-alpha. These results suggest that LOX-1 in macrophages may play an important role in Ox-LDL uptake and subsequent foam cell formation in this cell type.

  9. Rapamycin Inhibits Oxidized Low Density Lipoprotein Uptake in Human Umbilical Vein Endothelial Cells via mTOR/NF-κB/LOX-1 Pathway

    PubMed Central

    Liu, Zhi-Hua; Cao, Yong-Jun; Liu, Chun-Feng; Zhang, Yan-Lin; Xie, Ying

    2016-01-01

    Background Lectin-like oxidized low-density lipoprotein-1 (LOX-1) is the major receptor for oxidized low density lipoprotein (ox-LDL) uptake in human umbilical vein endothelial cells (HUVECs). Previously, we found that rapamycin inhibited ox-LDL accumulation in HUVECs, and this effect was related to its role in increasing the activity of autophagy-lysosome pathway. In this study, we determined whether rapamycin could also reduce ox-LDL uptake in HUVECs and investigated the underlying signaling mechanisms. Results Flow cytometry and live cell imaging showed that rapamycin reduced Dil-ox-LDL accumulation in HUVECs. Furthermore, rapamycin reduced the ox-LDL-induced increase in LOX-1 mRNA and protein levels. Western blotting showed that rapamycin inhibited mechanistic target of rapamycin (mTOR), p70s6k and IκBα phosphorylation triggered by ox-LDL. Flow cytometry implied that mTOR, NF-κB knockdown and NF-κB inhibitors significantly reduced Dil-ox-LDL uptake. Moreover, immunofluorescent staining showed that rapamycin reduced the accumulation of p65 in the nucleus after ox-LDL treatment for 30 h. mTOR knockdown decreased LOX-1 protein production and IκBα phosphorylation induced by ox-LDL. NF-κB knockdown and NF-κB inhibitors reduced LOX-1 protein production, but did not inhibit mTOR phosphorylation stimulated by ox-LDL. Conclusions These findings demonstrate that rapamycin reduce mTOR phosphorylation and subsequently inhibit NF-κB activation and suppresses LOX-1, resulting in a reduction in ox-LDL uptake in HUVECs. PMID:26752047

  10. Degree of oxidation of low density lipoprotein affects expression of CD36 and PPARgamma, but not cytokine production, by human monocyte-macrophages.

    PubMed

    Kavanagh, Ian C; Symes, Carole E; Renaudin, Pauline; Nova, Esther; Mesa, Maria Dolores; Boukouvalas, George; Leake, David S; Yaqoob, Parveen

    2003-06-01

    Oxidized low-density lipoprotein (oxLDL) exhibits many atherogenic effects, including the promotion of monocyte recruitment to the arterial endothelium and the induction of scavenger receptor expression. However, while atherosclerosis involves chronic inflammation within the arterial intima, it is unclear whether oxLDL alone provides a direct inflammatory stimulus for monocyte-macrophages. Furthermore, oxLDL is not a single, well-defined entity, but has structural and physical properties which vary according to the degree of oxidation. We tested the hypothesis that the biological effects of oxLDL will vary according to its degree of oxidation and that some species of oxLDL will have atherogenic properties, while other species may be responsible for its inflammatory activity. The atherogenic and inflammatory properties of LDL oxidized to predetermined degrees (mild, moderate and extensive oxidation) were investigated in a single system using human monocyte-derived macrophages. Expression of CD36 mRNA was up-regulated by mildly- and moderately-oxLDL, but not highly-oxLDL. The expression of the transcription factor, proliferator-activated receptor-gamma (PPARgamma), which has been proposed to positively regulate the expression of CD36, was increased to the greatest degree by highly-oxLDL. However, the DNA binding activity of PPARgamma was increased only by mildly- and moderately-oxLDL. None of the oxLDL species appeared to be pro-inflammatory towards monocytes, either directly or indirectly through mediators derived from lymphocytes, regardless of the degree of oxidation.

  11. Antioxidant capacity of oat (Avena sativa L.) extracts. 1. Inhibition of low-density lipoprotein oxidation and oxygen radical absorbance capacity.

    PubMed

    Handelman, G J; Cao, G; Walter, M F; Nightingale, Z D; Paul, G L; Prior, R L; Blumberg, J B

    1999-12-01

    Milled oat groat pearlings, trichomes, flour, and bran were extracted with methanol and the fractions tested in vitro for antioxidant capacity against low-density lipoprotein (LDL) oxidation and R-phycoerythrin protein oxidation in the oxygen radical absorbance capacity (ORAC) assay. The oxidative reactions were generated by 2,2'-azobis(2-amidinopropane) HCl (AAPH) or Cu(2+) in the LDL assay and by AAPH or Cu(2+) + H(2)O(2) in the ORAC assay and calibrated against a Trolox standard to calculate Trolox equivalents (1 Trolox equivalent = 1 TE = activity of 1 micromol of Trolox). The antioxidant capacity of the oat fractions was generally consistent with a potency rank of pearlings (2.89-8.58 TE/g) > flour (1.00-3.54 TE/g) > trichome (1.74 TE/g) = bran (1.02-1.62 TE/g) in both LDL and ORAC assays regardless of the free radical generator employed. A portion of the oat antioxidant constituents may be heat labile as the greatest activity was found among non-steam-treated pearlings. The contribution of oat tocols from the fractions accounted for <5% of the measured antioxidant capacity. AAPH-initiated oxidation of LDL was inhibited by the oat fractions in a dose-dependent manner, although complete suppression was not achieved with the highest doses tested. In contrast, Cu(2+)-initiated oxidation of LDL stimulated peroxide formation with low oat concentrations but completely inhibited oxidation with higher doses. Thus, oats possess antioxidant capacity most of which is likely derived from polar phenolic compounds in the aleurone. PMID:10606548

  12. Recognition of oxidized low density lipoprotein by the scavenger receptor of macrophages results from derivatization of apolipoprotein B by products of fatty acid peroxidation.

    PubMed

    Steinbrecher, U P; Lougheed, M; Kwan, W C; Dirks, M

    1989-09-15

    Uptake of cholesterol-containing lipoproteins by macrophages in the arterial intima is believed to be an important step in the pathogenesis of atherosclerosis. There are a number of possible mechanisms by which macrophages might accumulate cholesterol, and one that has attracted much interest recently involves the uptake of oxidatively modified low density lipoprotein (LDL) via a specific cell surface receptor, termed the scavenger or acetyl-LDL receptor. Previous studies have shown that chemical derivatization of LDL with reagents that result in neutralization of the charge of lysine amino groups also allows recognition by this receptor. As well, it has been shown that oxidation of LDL is accompanied by a decrease in free lysine groups and binding of lipid products to apolipoprotein B. The present studies were done to further characterize the receptor-binding domain on oxidized LDL. It was found that LDL could be modified by incubation with water-soluble products derived from autoxidized unsaturated fatty acids under conditions that inhibited oxidation of the LDL itself. The LDL modified in this way had increased electrophoretic mobility but showed no evidence of the oxidative damage that typifies LDL oxidized by exposure to metal ions. Furthermore, the oxidation product-modified LDL was rapidly degraded by cultured macrophages through the scavenger receptor pathway. Bovine albumin modified by oxidation products also showed greatly accelerated degradation by macrophages. When analyzed by reverse-phase high pressure liquid chromatography, the reactive oxidation products appeared less polar than fatty acids or simple medium-chain aldehydes. When treated with the carbonyl reagent 2,4-dinitrophenylhydrazine, the reactive fractions yielded derivatives, some of which were identified by mass spectrometry as hydrazones of nonenal, heptenal, pentenal, and crotonaldehyde. A series of 2-unsaturated aldehydes (acrolein to 2-nonenal) were all found to modify LDL, but none of

  13. Photochemiluminescent detection of antiradical activity. VI. Antioxidant characteristics of human blood plasma, low density lipoprotein, serum albumin and amino acids during in vitro oxidation.

    PubMed

    Popov, I; Lewin, G

    1999-01-01

    During investigation of the mechanism of therapeutic efficacy of UV (254 nm)-irradiated autologous blood, the antioxidant capacity (AC) of plasma, serum albumin, 20 amino acids, uric acid, ascorbic acid and alpha-tocopherol was measured after irradiation in vitro. AC of plasma demonstrated a biphasic time course (decrease to in a minimum (greater zero) followed by an increase). AC of uric acid, ascorbic acid and alpha-tocopherol diminished under irradiation to zero. In contrast, albumin and seven amino acids developed AC following irradiation. During the Cu(+2)-induced oxidation of low-density lipoprotein (LDL), the AC measured in a system for water-soluble substances appeared, after a lag-phase, to be comparable to that of the conjugated diene formation; AC of LDL measured in a system for lipid-soluble substances demonstrated a biphasic course. Our results suggest that: (a) the oxidized products of some amino acids and proteins acquire antiradical properties at the same time that they are being produced; (b) the biphasic character of changes of antioxidant properties of blood plasma during UV irradiation represents the overlapping of two processes: disappearing of antioxidants and acquisition of AC by (lipo)proteins; and (c) the measurement of AC of blood plasma (lipo)proteins can possibly serve to detect the existence and extent of oxidative stress in human organism.

  14. A1M/α1-microglobulin is proteolytically activated by myeloperoxidase, binds its heme group and inhibits low density lipoprotein oxidation

    PubMed Central

    Cederlund, Martin; Deronic, Adnan; Pallon, Jan; Sørensen, Ole E.; Åkerström, Bo

    2015-01-01

    α1-microglobulin (A1M) is a 26 kDa plasma and tissue protein with reductase activity and radical- and heme-binding anti-oxidative functions. In addition, exposure of A1M to hemoglobin has been shown to induce proteolytic elimination of a C-terminal tetrapeptide yielding a heme-degrading form, truncated A1M (t-A1M). Myeloperoxidase (MPO), a heme-containing enzyme that catalyzes the production of free radicals and hypochlorite, is released by neutrophils during the inflammatory response to bacterial infections. MPO-induced low density lipoprotein (LDL)-oxidation in blood has been suggested as a causative factor in atherosclerosis. In this study we have hypothesized that A1M interacts with MPO in a similar mode as with hemoglobin, and is a regulator of its activity. The results show that A1M is proteolytically cleaved, with formation of t-A1M, after exposure to MPO, and that t-A1M contains iron and heme-degradation products. The reaction is dependent of pH, time and concentration of substrates and a pH-value around 7 is shown to be optimal for cleavage. Furthermore, A1M inhibits MPO- and hydrogen peroxide-induced oxidation of LDL. The results suggest that A1M may have a role as an inhibitor of the damaging effects of the neutrophil respiratory burst on bystander tissue components. PMID:25698971

  15. Investigation of space charge distribution of low-density polyethylene/GO-GNF (graphene oxide from graphite nanofiber) nanocomposite for HVDC application.

    PubMed

    Kim, Yoon Jin; Ha, Son-Tung; Lee, Gun Joo; Nam, Jin Ho; Ryu, Ik Hyun; Nam, Su Hyun; Park, Cheol Min; In, Insik; Kim, Jiwan; Han, Chul Jong

    2013-05-01

    This paper reported a research on space charge distribution in low-density polyethylene (LDPE) nanocomposites with different types of graphene and graphene oxide (GO) at low filler content (0.05 wt%) under high DC electric field. Effect of addition of graphene oxide or graphene, its dispersion in LDPE polymer matrix on the ability to suppress space charge generation will be investigated and compared with MgO/LDPE nanocomposite at the same filler concentration. At an applied electric field of 80 kV/mm, a positive packet-like charge was observed in both neat LDPE, MgO/LDPE, and graphene/LDPE nanocomposites, whereas only little homogenous space charge was observed in GO/LDPE nanocomposites, especially with GO synthesized from graphite nano fiber (GNF) which is only -100 nm in diameter. Our research also suggests that dispersion of graphene oxide particles on the polymer matrix plays a significant role to the performance of nanocomposites on suppressing packet-like space charge. From these results, it is expected that nano-sized GO synthesized from GNF can be a promising filler material to LDPE composite for HVDC applications.

  16. Glycation and glycoxidation of low-density lipoproteins by glucose and low-molecular mass aldehydes. Formation of modified and oxidized particles.

    PubMed

    Knott, Heather M; Brown, Bronwyn E; Davies, Michael J; Dean, Roger T

    2003-09-01

    Patients with diabetes mellitus suffer from an increased incidence of complications including cardiovascular disease and cataracts; the mechanisms responsible for this are not fully understood. One characteristic of such complications is an accumulation of advanced glycation end-products formed by the adduction of glucose or species derived from glucose, such as low-molecular mass aldehydes, to proteins. These reactions can be nonoxidative (glycation) or oxidative (glycoxidation) and result in the conversion of low-density lipoproteins (LDL) to a form that is recognized by the scavenger receptors of macrophages. This results in the accumulation of cholesterol and cholesteryl esters within macrophages and the formation of foam cells, a hallmark of atherosclerosis. The nature of the LDL modifications required for cellular recognition and unregulated uptake are poorly understood. We have therefore examined the nature, time course, and extent of LDL modifications induced by glucose and two aldehydes, methylglyoxal and glycolaldehyde. It has been shown that these agents modify Arg, Lys and Trp residues of the apoB protein of LDL, with the extent of modification induced by the two aldehydes being more rapid than with glucose. These processes are rapid and unaffected by low concentrations of copper ions. In contrast, lipid and protein oxidation are slow processes and occur to a limited extent in the absence of added copper ions. No evidence was obtained for the stimulation of lipid or protein oxidation by glucose or methylglyoxal in the presence of copper ions, whereas glycolaldehyde stimulated such reactions to a modest extent. These results suggest that the earliest significant events in this system are metal ion-independent glycation (modification) of the protein component of LDL, whilst oxidative events (glycoxidation or direct oxidation of lipid or proteins) only occur to any significant extent at later time points. This 'carbonyl-stress' may facilitate the formation

  17. Effect of ezetimibe/atorvastatin combination on oxidized low density lipoprotein cholesterol in patients with coronary artery disease or coronary artery disease equivalent.

    PubMed

    Azar, Rabih R; Badaoui, Georges; Sarkis, Antoine; Azar, Mireille; Aydanian, Herminé; Harb, Serge; Achkouty, Guy; Kassab, Roland

    2010-07-15

    Ezetimibe is effective in providing additional low-density lipoprotein (LDL) cholesterol lowering when coadministered with statins, but its effect beyond LDL cholesterol lowering is unknown. Oxidized LDL (ox-LDL) is a better predictor of adverse cardiovascular events than standard lipid parameters. The objective of this study was to investigate the effect of ezetimibe on ox-LDL. A total of 100 patients with coronary artery disease or coronary artery disease equivalent were randomized to atorvastatin 40 mg/day and ezetimibe 10 mg/day or to atorvastatin 40 mg/day and placebo. LDL cholesterol, LDL cholesterol subfractions, and ox-LDL were measured at baseline and after 8 weeks of therapy. The ezetimibe group had a larger reduction in total LDL cholesterol compared to placebo. This was due mainly to a larger reduction in large buoyant LDL (24% vs 10%, p = 0.008). Ox-LDL level did not change in the placebo group (50 +/- 13 vs 51 +/- 13 U/L), while it decreased in the ezetimibe group, from 51 +/- 13 to 46 +/- 10 U/L (p = 0.01 vs baseline and p = 0.02 vs final level in placebo). The change in ox-LDL correlated significantly with those in total LDL and in large buoyant LDL (r = 0.6 and r = 0.5, respectively, p <0.01 for both), but not with that of small dense LDL, high-density lipoprotein, or very low density lipoprotein. In conclusion, this study demonstrates that ezetimibe decreases ox-LDL cholesterol through reductions in total LDL cholesterol and in large buoyant LDL cholesterol.

  18. Nitric oxide inhibition of lipoxygenase-dependent liposome and low-density lipoprotein oxidation: termination of radical chain propagation reactions and formation of nitrogen-containing oxidized lipid derivatives.

    PubMed

    Rubbo, H; Parthasarathy, S; Barnes, S; Kirk, M; Kalyanaraman, B; Freeman, B A

    1995-12-01

    Lipoxygenase-induced lipid oxidation contributes to plasma lipoprotein oxidation and may be an underlying pathogenic mechanism of atherogenesis. Since inactivation of the vasorelaxant actions of nitric oxide (.NO) plays a critical role in the impaired function of atherosclerotic vessels and because .NO reacts rapidly with other radical species, we assessed the influence of .NO on lipoxygenase-catalyzed oxidation of linoleic and linolenic acid, 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (PC) liposomes, hypercholesterolemic rabbit beta-very-low-density lipoprotein, and human low-density lipoprotein. Soybean lipoxygenase (SLO)-induced lipid oxidation was assessed by accumulation of conjugated dienes, formation of lipid hydroperoxides, oxygen consumption, and liquid chromatography-mass spectrometry. Different rates of delivery of .NO to lipid oxidation systems were accomplished either by infusion of .NO gas equilibrated with anaerobic buffer or via .NO released from S-nitrosoglutathione. Nitric oxide alone did not induce lipid peroxidation, while exposure to SLO yielded significant oxidation of fatty acids, PC liposomes, or lipoproteins in a metal ion-independent mechanism. Low concentrations of .NO, which did not significantly inhibit the activity of the iron-containing lipoxygenase, induced potent inhibition of lipid peroxidation in a dose-dependent manner. Mass spectral analysis of oxidation products showed formation of nitrito-, nitro-, nitrosoperoxo-, and/or nitrated lipid oxidation adducts, demonstrating that .NO serves as a potent terminator of radical chain propagation reactions. The formation of Schiff's base fluorescent conjugates between SLO-oxidized linoleic or linolenic acid and bovine serum albumin (BSA) was also inhibited by .NO via reaction with lipid hydroperoxyl radicals (LOO.), thus preventing the reaction of LOO. with polypeptide amino groups. Mass spectrometry analysis showed that both lipid peroxidation products and nitrogen

  19. Oxide-free InAs(111)A interface in metal-oxide-semiconductor structure with very low density of states prepared by anodic oxidation

    SciTech Connect

    Valisheva, N. A. Aksenov, M. S.; Golyashov, V. A.; Levtsova, T. A.; Kovchavtsev, A. P.; Gutakovskii, A. K.; Tereshchenko, O. E.; Khandarkhaeva, S. E.; Kalinkin, A. V.; Prosvirin, I. P.; Bukhtiyarov, V. I.

    2014-10-20

    In this letter, we present structural, compositional, and electrical characteristics of anodic oxide layer-based metal-oxide-semiconductor (MOS) capacitors on n-type InAs(111)A, along with the effect of a thin fluorinated interfacial passivation layer. Electrochemical oxidation in acid electrolyte with addition of fluorine (NH{sub 4}F) led to the formation of oxygen free well-ordered wide gap fluorinated interfacial layer at InAs(111)A with the fixed charge (Q{sub fix}) and density of interface states (D{sub it}) in the range of (4–6) × 10{sup 10 }cm{sup −2} and (2–12) × 10{sup 10 }eV{sup −1 }cm{sup −2}, respectively. We found that MOS capacitors showed excellent capacitance-voltage characteristics with very small frequency dispersion (<1% and <15 mV). Fluorinated interfacial layer consists of crystalline isostructural compound with the InAs substrate, which remains intact with the atomic smoothness and sharpness that explain unpinned behavior of the Fermi level.

  20. Phenolic-extract from argan oil (Argania spinosa L.) inhibits human low-density lipoprotein (LDL) oxidation and enhances cholesterol efflux from human THP-1 macrophages.

    PubMed

    Berrougui, Hicham; Cloutier, Martin; Isabelle, Maxim; Khalil, Abdelouahed

    2006-02-01

    Argan oil is rich in unsaturated fatty acids, tocopherol and phenolic compounds. These protective molecules make further study of its cardiovascular diseases (CVDs) action interesting. Furthermore, no previous study has explored the antioxidant activity of argan oil in comparison with olive oil. The present study was conducted to evaluate the beneficial properties of Virgin argan oil phenolic extracts (VAO-PE) towards CVD by: (A) protecting human (low-density lipoprotein, LDL) against lipid peroxidation and (B) promoting high-density lipoprotein (HDL)-mediated cholesterol efflux. Human LDLs were oxidized by incubation with CuSO(4) in the presence of different concentrations of VAO-PE (0-320mug/ml). LDL lipid peroxidation was evaluated by conjugated diene and MDA formation as well as Vitamin E disappearance. Incubation of LDL with VAO-PE significantly prolonged the lag-phase and lowered the progression rate of lipid peroxidation (P<0.01) and reduced the disappearance of Vitamin E in a concentration-dependent manner. Incubation of HDL with VAO-PE significantly increased the fluidity of the HDL phospholipidic bilayer (P=0.0004) and HDL-mediated cholesterol efflux from THP-1 macrophages. These results suggest that Virgin argan oil provides a source of dietary phenolic antioxidants, which prevent cardiovascular diseases by inhibiting LDL-oxidation and enhancing reverse cholesterol transport. These properties increase the anti-atherogenic potential of HDL. PMID:16019008

  1. Phenolic-extract from argan oil (Argania spinosa L.) inhibits human low-density lipoprotein (LDL) oxidation and enhances cholesterol efflux from human THP-1 macrophages.

    PubMed

    Berrougui, Hicham; Cloutier, Martin; Isabelle, Maxim; Khalil, Abdelouahed

    2006-02-01

    Argan oil is rich in unsaturated fatty acids, tocopherol and phenolic compounds. These protective molecules make further study of its cardiovascular diseases (CVDs) action interesting. Furthermore, no previous study has explored the antioxidant activity of argan oil in comparison with olive oil. The present study was conducted to evaluate the beneficial properties of Virgin argan oil phenolic extracts (VAO-PE) towards CVD by: (A) protecting human (low-density lipoprotein, LDL) against lipid peroxidation and (B) promoting high-density lipoprotein (HDL)-mediated cholesterol efflux. Human LDLs were oxidized by incubation with CuSO(4) in the presence of different concentrations of VAO-PE (0-320mug/ml). LDL lipid peroxidation was evaluated by conjugated diene and MDA formation as well as Vitamin E disappearance. Incubation of LDL with VAO-PE significantly prolonged the lag-phase and lowered the progression rate of lipid peroxidation (P<0.01) and reduced the disappearance of Vitamin E in a concentration-dependent manner. Incubation of HDL with VAO-PE significantly increased the fluidity of the HDL phospholipidic bilayer (P=0.0004) and HDL-mediated cholesterol efflux from THP-1 macrophages. These results suggest that Virgin argan oil provides a source of dietary phenolic antioxidants, which prevent cardiovascular diseases by inhibiting LDL-oxidation and enhancing reverse cholesterol transport. These properties increase the anti-atherogenic potential of HDL.

  2. Fatty acid synthase/oxidized low-density lipoprotein as metabolic oncogenes linking obesity to colon cancer via NF-kappa B in Egyptians.

    PubMed

    Keshk, Walaa Arafa; Zineldeen, Doaa Hussein; Wasfy, Rania E L-sayed; El-Khadrawy, Osama Helmy

    2014-10-01

    Obesity is a major health problem which heightens the risk of several chronic illnesses including cancer development particularly colon cancer. The underlying pathophysiology of obesity associated colon cancer remains to be elucidated. The purpose of this current study was to determine fatty acid synthase (FASN) activity/expression, oxidized low-density lipoprotein (ox-LDL) level and redox status under the context of anthropometric measurements and lipid profile to find their potential role as interacting biomarkers relating obesity to colon cancer initiation and progression via nuclear factor kappa-B (NF-κB) signaling. This study was conducted upon Egyptian individuals; 30 obese subjects with colon cancer, 11 nonobese and 11 obese subjects without colon cancer. FASN gene expression, NF-κB immunoreactivity, and serum ox-LDL level were estimated by real-time PCR, immunohistochemistry and immunoassay, respectively. FASN activity, glycemic status, obesity, and oxidative stress indices were also assessed. It was found that FASN expression and activity were statistically increased in obese with colon cancer (P=0.021 and 0.018, respectively), with statistically significant increase in patients with advanced grading. Moreover, NF-κB immunoreactivity and serum ox-LDL level were significantly increased in obese colon cancer patients with significantly higher levels in those with advanced grading (all P<0.05). Dyslipidemia, insulin resistance, and oxidative stress indices were worsened in obese patients with colon cancer. These results revealed that FASN and ox-LDL as well as oxidative stress may increase the risk of obesity related colon cancer, particularly via NF-κB signaling and could be used as potential predictive and prognostic biomarkers for obesity complicated with colon cancer.

  3. Chemical structures of 4-oxo-flavonoids in relation to inhibition of oxidized low-density lipoprotein (LDL)-induced vascular endothelial dysfunction.

    PubMed

    Yi, Long; Jin, Xin; Chen, Chun-Ye; Fu, Yu-Jie; Zhang, Ting; Chang, Hui; Zhou, Yong; Zhu, Jun-Dong; Zhang, Qian-Yong; Mi, Man-Tian

    2011-01-01

    Vascular endothelial dysfunction induced by oxidative stress has been demonstrated to be the initiation step of atherosclerosis (AS), and flavonoids may play an important role in AS prevention and therapy. Twenty-three flavonoids categorized into flavones, flavonols, isoflavones, and flavanones, all with 4-oxo-pyronenucleus, were examined for what structural characteristics are required for the inhibitory effects on endothelial dysfunction induced by oxidized low-density lipoprotein (oxLDL). Human vascular endothelial cells EA.hy926 were pretreated with different 4-oxo-flavonoids for 2 hs, and then exposed to oxLDL for another 24 hs. Cell viability and the level of malondialdehyde (MDA), nitric oxide (NO) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured, respectively. Then, correlation analysis and paired comparison were used to analyze the structure-activity relationships. Significant correlations were observed between the number of -OH moieties in total or in B-ring and the inhibitory effectson endothelial dysfunction. Furthermore, 3',4'-ortho-dihydroxyl on B-ring, 3-hydroxyl on C-ring and 2,3-double bondwere correlated closely to the inhibitory effects of flavonolson cell viability decrease and lipid peroxidation. 5,7-meta-dihydroxyl group on A-ring was crucial for the anti-inflammatory effects of flavones and isoflavones in endothelial cells. Moreover, the substituted position of B-ring on C3 rather than C2 was important for NO release. Additionally, hydroxylation at C6 position significantly attenuated the inhibitory effects of 4-oxo-flavonoids on endothelial dysfunction. Our findings indicated that the effective agents in inhibiting endothelial dysfunction include myricetin, quercetin, luteolin, apigenin, genistein and daidzein. Our work might provide some evidence for AS prevention and a strategy for the design of novel AS preventive agents.

  4. Cell surface expression of mouse macrosialin and human CD68 and their role as macrophage receptors for oxidized low density lipoprotein.

    PubMed

    Ramprasad, M P; Terpstra, V; Kondratenko, N; Quehenberger, O; Steinberg, D

    1996-12-10

    We have previously identified a 94- to 97-kDa oxidized low density lipoprotein (LDL)-binding protein in mouse macrophages as macrosialin (MS), a member of the lamp family. Earlier immunostaining studies have shown that MS and its human homolog, CD68, are predominantly intracellular proteins. However, using sensitive techniques such as flow cytometry (FACS) and cell-surface-specific biotinylation, we now show that there is significant surface expression of these proteins. FACS analysis of intact cells using mAb FA/11 showed small but definite surface expression of MS in resident mouse peritoneal macrophages but this was greatly enhanced with thioglycollate elicitation. Biotinylation of intact cells and detergent-solubilized cell preparations followed by immunoprecipitation revealed 10-15% of the total MS content of elicited macrophages on the plasma membrane. Similar results were obtained with untreated RAW 264.7 cells. FACS analysis of intact THP-1 monocytic cells showed minimal surface expression of CD68 on unactivated cells (4% of total cell content). Stimulation with phorbol 12-myristate 13-acetate increased both surface and total CD68 expression considerably. Furthermore, the specific binding at 4 degrees C and uptake at 37 degrees C of 125I-labeled oxidized LDL by activated THP-1 cells was inhibited by 30-50% by CD68 mAbs KP-1 and EBM-11. Thus, although the surface expression of MS/CD68 at steady-state represents only a small percentage of their total cellular content, these proteins can play a significant role in oxidized LDL uptake by activated macrophages in vitro and could contribute to foam cell formation in atherosclerotic lesions.

  5. Inhibition of Glutathione Production Induces Macrophage CD36 Expression and Enhances Cellular-oxidized Low Density Lipoprotein (oxLDL) Uptake.

    PubMed

    Yang, Xiaoxiao; Yao, Hui; Chen, Yuanli; Sun, Lei; Li, Yan; Ma, Xingzhe; Duan, Shengzhong; Li, Xiaoju; Xiang, Rong; Han, Jihong; Duan, Yajun

    2015-09-01

    The glutathione (GSH)-dependent antioxidant system has been demonstrated to inhibit atherosclerosis. Macrophage CD36 uptakes oxidized low density lipoprotein (oxLDL) thereby facilitating foam cell formation and development of atherosclerosis. It remains unknown if GSH can influence macrophage CD36 expression and cellular oxLDL uptake directly. Herein we report that treatment of macrophages with l-buthionine-S,R-sulfoximine (BSO) decreased cellular GSH production and ratios of GSH to glutathione disulfide (GSH/GSSG) while increasing production of reactive oxygen species. Associated with decreased GSH levels, macrophage CD36 expression was increased, which resulted in enhanced cellular oxLDL uptake. In contrast, N-acetyl cysteine and antioxidant enzyme (catalase or superoxide dismutase) blocked BSO-induced CD36 expression as well as oxLDL uptake. In vivo, administration of mice with BSO increased CD36 expression in peritoneal macrophages and kidneys. BSO had no effect on CD36 mRNA expression and promoter activity but still induced CD36 protein expression in macrophages lacking peroxisome proliferator-activated receptor γ expression, suggesting it induced CD36 expression at the translational level. Indeed, we determined that BSO enhanced CD36 translational efficiency. Taken together, our study demonstrates that cellular GSH levels and GSH/GSSG status can regulate macrophage CD36 expression and cellular oxLDL uptake and demonstrate an important anti-atherogenic function of the GSH-dependent antioxidant system by providing a novel molecular mechanism.

  6. Inhibition of lectin-like oxidized low-density lipoprotein receptor-1 reduces cardiac fibroblast proliferation by suppressing GATA Binding Protein 4.

    PubMed

    Liu, Bin; Liu, Ning-Ning; Liu, Wei-Hua; Zhang, Shuang-Wei; Zhang, Jing-Zhi; Li, Ai-Qun; Liu, Shi-Ming

    2016-07-01

    Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and GATA Binding Protein 4 (GATA4) are important for the growth of cardiac fibroblasts (CFs). When deregulated, LOX-1 and GATA4 can cause cardiac remodeling. In the present study, we found novel evidence that GATA4 was required for the LOX-1 regulation of CF proliferation. The inhibition of LOX-1 by RNA interference LOX-1 lentivirus resulted in the loss of PI3K/Akt activation and GATA4 protein expression. The overexpression of LOX-1 by lentivirus rescued CF proliferation, PI3K/Akt activation, and GATA4 protein expression. Moreover, GATA4 overexpression enhanced CF proliferation with LOX-1 inhibition. We also found that the inhibition of PI3K/Akt activation by LY294002, a PI3K inhibitor, reduced cell proliferation and protein level of GATA4. In summary, GATA4 may play an important role in the LOX-1 and PI3K/Akt regulation of CF proliferation. PMID:27216460

  7. Inhibition of p38 Mitogen-Activated Protein Kinase Enhances the Apoptosis Induced by Oxidized Low-Density Lipoprotein in Endothelial Progenitor Cells.

    PubMed

    Tie, Guodong; Yan, Jinglian; Messina, Julia A; Raffai, Robert L; Messina, Louis M

    2015-01-01

    Oxidized low-density lipoprotein (oxLDL) is an important risk factor in the development of atherosclerosis. oxLDL has been shown to decrease endothelial progenitor cell (EPC) number by inducing apoptosis. p38 mitogen-activated protein kinase (MAPK) was shown to be activated by oxLDL and participated in the regulation of EPC number and function. However, the role of p38 remains unknown. Here, we show that oxLDL-induced p38 phosphorylation in EPCs is time and dose dependent. Treatment with antioxidant N-acetyl cysteine restored oxLDL-induced p38 phosphorylation to basal levels. LOX-1-blocking antibody also significantly decreased oxLDL-induced p38 phosphorylation. Interestingly, TUNEL staining showed that pretreatment with the p38 inhibitor SB203580 further increased oxLDL-induced apoptosis in EPCs. In accordance with these findings, pretreatment with SB203580 further attenuated Akt phosphorylation in EPCs challenged with oxLDL, indicating an interaction between Akt and p38 MAPK pathways. In agreement, inhibition of p38 MAPK further attenuated Akt phosphorylation and increased apoptosis in EPCs isolated from hypercholesterolemic ApoE-/- mice. In conclusion, p38 MAPK serves as an anti-apoptotic pathway by supporting Akt activity when EPCs are challenged with oxLDL. PMID:27031525

  8. Effects of Bulbus allii macrostemi on clinical outcomes and oxidized low-density lipoprotein and plasminogen in unstable angina/non-ST-segment elevation myocardial infarction patients.

    PubMed

    Liu, Yan; Zhang, Lei; Liu, Yun-Fang; Yan, Fang-Fang; Zhao, Yu-Xia

    2008-11-01

    Unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) is associated with an increased risk of cardiac death and an efficacious drug with few side effects is necessary. The study aimed to evaluate the effects of Bulbus allii macrostemi (B. macrostemi) on UA/NSTEMI patients as well as to elucidate possible mechanisms. 79 patients were randomly divided into two groups: the trial group received B. macrostemi plus baseline therapy, the control group was given placebo plus baseline therapy. The trial lasted 8 weeks. The evaluation involved main clinical symptoms, changes of electrocardiogram and biochemical examination. After treatment, the trial group showed more significant improvement on clinical manifestation. The plasma oxidized low-density lipoprotein (ox-LDL) level decreased significantly in the trial group (p < 0.01); the plasminogen activator inhibitor-1 (PAI-1) level decreased in both groups and it decreased more significantly in the trial group (p < 0.01). In contrast, the activity of plasminogen (PLG) increased in both groups and the change was more marked in the trial group (p < 0.01). The results suggested that B. macrostemi combined with baseline therapy could improve clinical symptoms of UA/NSTEMI patients by decreasing the ox-LDL and PAI-1 levels and enhancing the activity of PLG. PMID:18688814

  9. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation

    NASA Astrophysics Data System (ADS)

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-08-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

  10. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.

    PubMed

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-01-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease. PMID:27488468

  11. Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation.

    PubMed

    Liu, Liang; Gao, Chao; Yao, Ping; Gong, Zhiyong

    2015-01-01

    A growing body of evidence has indicated that high-fat diet-induced nonalcoholic fatty liver disease is usually accompanied by oxidized low-density lipoprotein (ox-LDL) deposited in the liver. The current study aimed to investigate the effect of quercetin on high-fat diet-induced ox-LDL accumulation in the liver and to explore the potential underlying mechanisms. The results demonstrate that quercetin supplementation for 24 weeks significantly alleviated high-fat diet-induced liver damage and reduced hepatic cholesterol and ox-LDL level. Quercetin notably inhibited both mRNA and protein expression of CD36 (reduced by 53% and 71%, resp.) and MSR1 (reduced by 25% and 45%, resp.), which were upregulated by high-fat diet. The expression of LC3II was upregulated by 2.4 times whereas that of p62 and mTOR was downregulated by 57% and 63% by quercetin treatment. Therefore, the significantly improved autophagy lysosomal degradation capacity for ox-LDL may be implicated in the hepatoprotective effect of quercetin; scavenger receptors mediated ox-LDL uptake might also be involved.

  12. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.

    PubMed

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-08-04

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

  13. Pdcd4 Is Involved in the Formation of Stress Granule in Response to Oxidized Low-Density Lipoprotein or High-Fat Diet

    PubMed Central

    Bai, Yang; Dong, Zhaojing; Shang, Qianwen; Zhao, Hui; Wang, Liyang; Guo, Chun; Gao, Fei; Zhang, Lining; Wang, Qun

    2016-01-01

    Stress granules (SGs) in response to various stresses have been reported in many diseases. We previously reported the implication of programmed cell death 4 (Pdcd4) in obesity-induced stress responses, but the possible link between Pdcd4 and SGs remains lacking. In this study we showed that oxidized low-density lipoprotein (ox-LDL) or high-fat diet (HFD) induced SG formation in mouse macrophages and liver tissues, and Pdcd4 deficiency in mice remarkably reduced its formation. In response to ox-LDL, either endogenous or ectopic Pdcd4 displayed granule-like expression and co-localized with SG markers including T-cell-restricted intracellular antigen-1, fragile X mental retardation-related protein 1, and eukaryotic initiation factor 4A. Ectopic expression of truncated Pdcd4 that depleted specific RNA-binding motif significantly disrupted the SG formation, suggesting the direct involvement of Pdcd4 in ox-LDL-induced SGs through its RNA-binding activity. Additionally, Pdcd4 deficiency drove AKT activation and suppression of eIF2α phosphorylation, thereby contributing to the resistance to ox-LDL or HFD-induced SG formation. Collectively, our data suggest that Pdcd4 as a crucial regulator in SGs induced by ox-LDL or HFD maybe a potential target for mitigating SG-associated stress responses in obesity and related diseases. PMID:27454120

  14. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation

    PubMed Central

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-01-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease. PMID:27488468

  15. Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation

    PubMed Central

    Liu, Liang; Gao, Chao; Yao, Ping; Gong, Zhiyong

    2015-01-01

    A growing body of evidence has indicated that high-fat diet-induced nonalcoholic fatty liver disease is usually accompanied by oxidized low-density lipoprotein (ox-LDL) deposited in the liver. The current study aimed to investigate the effect of quercetin on high-fat diet-induced ox-LDL accumulation in the liver and to explore the potential underlying mechanisms. The results demonstrate that quercetin supplementation for 24 weeks significantly alleviated high-fat diet-induced liver damage and reduced hepatic cholesterol and ox-LDL level. Quercetin notably inhibited both mRNA and protein expression of CD36 (reduced by 53% and 71%, resp.) and MSR1 (reduced by 25% and 45%, resp.), which were upregulated by high-fat diet. The expression of LC3II was upregulated by 2.4 times whereas that of p62 and mTOR was downregulated by 57% and 63% by quercetin treatment. Therefore, the significantly improved autophagy lysosomal degradation capacity for ox-LDL may be implicated in the hepatoprotective effect of quercetin; scavenger receptors mediated ox-LDL uptake might also be involved. PMID:26697490

  16. Inhibition of Glutathione Production Induces Macrophage CD36 Expression and Enhances Cellular-oxidized Low Density Lipoprotein (oxLDL) Uptake*

    PubMed Central

    Yang, Xiaoxiao; Yao, Hui; Chen, Yuanli; Sun, Lei; Li, Yan; Ma, Xingzhe; Duan, Shengzhong; Li, Xiaoju; Xiang, Rong; Han, Jihong; Duan, Yajun

    2015-01-01

    The glutathione (GSH)-dependent antioxidant system has been demonstrated to inhibit atherosclerosis. Macrophage CD36 uptakes oxidized low density lipoprotein (oxLDL) thereby facilitating foam cell formation and development of atherosclerosis. It remains unknown if GSH can influence macrophage CD36 expression and cellular oxLDL uptake directly. Herein we report that treatment of macrophages with l-buthionine-S,R-sulfoximine (BSO) decreased cellular GSH production and ratios of GSH to glutathione disulfide (GSH/GSSG) while increasing production of reactive oxygen species. Associated with decreased GSH levels, macrophage CD36 expression was increased, which resulted in enhanced cellular oxLDL uptake. In contrast, N-acetyl cysteine and antioxidant enzyme (catalase or superoxide dismutase) blocked BSO-induced CD36 expression as well as oxLDL uptake. In vivo, administration of mice with BSO increased CD36 expression in peritoneal macrophages and kidneys. BSO had no effect on CD36 mRNA expression and promoter activity but still induced CD36 protein expression in macrophages lacking peroxisome proliferator-activated receptor γ expression, suggesting it induced CD36 expression at the translational level. Indeed, we determined that BSO enhanced CD36 translational efficiency. Taken together, our study demonstrates that cellular GSH levels and GSH/GSSG status can regulate macrophage CD36 expression and cellular oxLDL uptake and demonstrate an important anti-atherogenic function of the GSH-dependent antioxidant system by providing a novel molecular mechanism. PMID:26187465

  17. Effects of soy pinitol on the pro-inflammatory cytokines and scavenger receptors in oxidized low-density lipoprotein-treated THP-1 macrophages.

    PubMed

    Choi, Myung-Sook; Lee, Won-Ha; Kwon, Eun-Young; Kang, Mi Ae; Lee, Mi-Kyung; Park, Yong Bok; Jeon, Seon-Min

    2007-12-01

    Pinitol, a methylated form of D-chiro-inositol, acts as a insulin mediator. We investigated the effects of soy pinitol on the factors involved in foam cell formation using differentiated THP-1 macrophages. Pinitol slightly inhibited the lipid-laden foam cell formation by oxidized low-density lipoprotein (oxLDL) in a dose-dependent manner. Tumor necrosis factor-alpha and monocyte chemoattractant protein-1 releases were significantly reduced by pinitol treatment (0.05-0.5 mM), whereas interleukin-1beta and interleukin-8 secretions were significantly reduced in low-dose pinitol (0.05 or 0.1 mM) and 0.5 mM pinitol-treated cells, respectively, compared to no pinitol-treated cells. Gene expressions of CD36 and CD68 were significantly down-regulated by 0.05-0.5 mM pinitol compared to the oxLDL-treated control cells. Matrix metalloproteinase-9 gene expression was significantly decreased in 0.05-0.5 mM pinitol-treated cells compared to the no pinitol-treated macrophages. We conclude that pinitol has some inhibitory effects on foam cell formation by reducing lipid accumulation, secretion, and expression of some cytokines and macrophage scavenger receptor expression via its insulin-like action.

  18. Pressurized water versus ethanol as a Silybum marianum extraction solvent for inhibition of low-density lipoprotein oxidation mediated by copper and J774 macrophage cells.

    PubMed

    Wallace, Sunny N; Raible, Jennifer; Carrier, Danielle Julie; Vaughn, Katherine L; Griffis, Carl L; Clausen, Edgar C; Nagarajan, Shanmugam

    2007-09-01

    Silybum marianum contains flavonolignans, termed silymarin (SM), that are therapeutic agents for many inflammation-based diseases including atherosclerosis. Oxidation of human low-density lipoprotein was induced by CuSO4 or J774 macrophage cells and measured by the formation of thiobarbituric acid reactive substances (TBARS). SM was extracted by pressurized hot water (PHWE) or ethanol, and the effects of these extracts on TBARS formation were evaluated in comparison with those of SM preparations made from blending masses of individual flavonolignan standards in ratios identical to those of the water and ethanol extracts. Ethanol-extracted SM and its blended counterpart inhibited the generation of TBARS by 82% and 43%, respectively, at 150 mumol/L doses. TBARS levels in the presence of 150 micromol/L of the PHWE and its blended SM counterpart were reduced by 84% and 38%, respectively. Extracts from milk thistle fruit displayed higher protective effects than blended SM solutions of the same concentration with an identical compositional makeup. The appearance of degradation peaks in the water extract did not create any cytotoxic effects. Results of this study confirm that PHWE can be used to extract flavonolignans from milk thistle and that these extracts may possess therapeutic potential different from or beyond that of traditional organic solvent preparations. PMID:18066135

  19. Protective effect of the silkworm protein 30Kc6 on human vascular endothelial cells damaged by oxidized low density lipoprotein (Ox-LDL).

    PubMed

    Yu, Wei; Ying, Huihui; Tong, Fudan; Zhang, Chen; Quan, Yanping; Zhang, Yaozhou

    2013-01-01

    Although the 30K family proteins are important anti-apoptotic molecules in silkworm hemolymph, the underlying mechanism remains to be investigated. This is especially the case in human vascular endothelial cells (HUVECs). In this study, a 30K protein, 30Kc6, was successfully expressed and purified using the Bac-to-Bac baculovirus expression system in silkworm cells. Furthermore, the 30Kc6 expressed in Escherichia coli was used to generate a polyclonal antibody. Western blot analysis revealed that the antibody could react specifically with the purified 30Kc6 expressed in silkworm cells. The In vitro cell apoptosis model of HUVEC that was induced by oxidized low density lipoprotein (Ox-LDL) and in vivo atherosclerosis rabbit model were constructed and were employed to analyze the protective effects of the silkworm protein 30Kc6 on these models. The results demonstrated that the silkworm protein 30Kc6 significantly enhanced the cell viability in HUVEC cells treated with Ox-LDL, decreased the degree of DNA fragmentation and markedly reduced the level of 8-isoprostane. This could be indicative of the silkworm protein 30Kc6 antagonizing the Ox-LDL-induced cell apoptosis by inhibiting the intracellular reactive oxygen species (ROS) generation. Furthermore, Ox-LDL activated the cell mitogen activated protein kinases (MAPK), especially JNK and p38. As demonstrated with Western analysis, 30Kc6 inhibited Ox-LDL-induced cell apoptosis in HUVEC cells by preventing the MAPK signaling pathways. In vivo data have demonstrated that oral feeding of the silkworm protein 30Kc6 dramatically improved the conditions of the atherosclerotic rabbits by decreasing serum levels of total triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Furthermore, 30Kc6 alleviated the extent of lesions in aorta and liver in the atherosclerotic rabbits. These data are not only helpful in understanding the anti

  20. Effects of low-density lipoproteins as additive on quality parameters and oxidative stress following cryopreservation of mithun (Bos frontalis) spermatozoa.

    PubMed

    Perumal, P; Srivastava, S K; Ghosh, S K; Baruah, K K; Bag, S; Rajoria, J S; Kumar, K; Rajkhowa, C; Pande, M; Srivastava, N

    2016-10-01

    Artificial breeding of mithun poses several challenges including lack of standard protocol for cryopreservation of spermatozoa. This is further complicated by harmful effects of hen's egg yolk (EY) as additive in extender. Purified low-density lipoproteins (LDL) extracted from EY have been shown as beneficial over EY extender for long-term semen storage in several species. This investigation explored use of LDL versus EY on semen quality and oxidative stress following freezing-thawing of spermatozoa. A total of 25 of 50 ejaculates based on biophysical parameters were selected for the experiment. After diluting with the Tris-citrate-glycerol (TCG) extender, each sample was split into three equal aliquots: Group I, control, EY; Group II and Group III contained 8% and 10% purified LDL, respectively. Frozen-thawed samples were evaluated for motility parameters (progressive, and in the bovine cervical mucus penetration test [BCMPT]), viability, sperm and nuclear abnormality, acrosome integrity, and enzymatic (leakage of intracellular contents) and biochemical (oxidative stress) profiles and in vitro fertility (IVF) assay. Study revealed a significant (p < .05) improvement in viability, sperm and nuclear abnormality, acrosome integrity, motility (progressive and in cervical mucus), cholesterol content, and reduction in the leakage of intracellular enzymes in Group II. Moreover, intactness of acrosome and biochemical membranes was protected significantly (p < .05) in addition to significant (p < .05) improvement in binding per cent and binding index in IVF assay in extender containing 8% LDL. These results demonstrate that although cryopreservation of mithun's spermatozoa in EY was comparable with other species, addition of 8% LDL holds a clear advantage over EY or 10% LDL. PMID:27418332

  1. MicroRNA-155 silencing enhances inflammatory response and lipid uptake in oxidized low-density lipoprotein-stimulated human THP-1 macrophages.

    PubMed

    Huang, Ri-sheng; Hu, Guan-qiong; Lin, Bin; Lin, Zhi-yi; Sun, Cheng-chao

    2010-12-01

    It has been proposed that the inflammatory response of monocytes/macrophages induced by oxidized low-density lipoprotein (oxLDL) is a key event in the pathogenesis of atherosclerosis. MicroRNA-155 (miR-155) is an important regulator of the immune system and has been shown to be involved in acute inflammatory response. However, the function of miR-155 in oxLDL-stimulated inflammation and atherosclerosis remains unclear. Here, we show that the exposure of human THP-1 macrophages to oxLDL led to a marked up-regulation of miR-155 in a dose-dependent manner. Silencing of endogenous miR-155 in THP-1 cells using locked nucleic acid-modified antisense oligonucleotides significantly enhanced oxLDL-induced lipid uptake, up-regulated the expression of scavenger receptors (lectinlike oxidized LDL receptor-1, cluster of differentiation 36 [CD36], and CD68), and promoted the release of several cytokines including interleukin (IL)-6, -8, and tumor necrosis factor α (TNF-α). Luciferase reporter assay showed that targeting miR-155 promoted nuclear factor-kappa B (NF-κB) nuclear translocation and potentiated the NF-κB-driven transcription activity. Moreover, miR-155 knockdown resulted in a marked increase in the protein amount of myeloid differentiation primary response gene 88 (MyD88), an important adapter protein used by Toll-like receptors to activate the NF-κB pathway. Our data demonstrate that miR-155 serves as a negative feedback regulator in oxLDL-stimulated THP-1 inflammatory responses and lipid uptake and thus might have potential therapeutic implications in atherosclerosis.

  2. Lectin-like oxidized low-density lipoprotein receptor-1 abrogation causes resistance to inflammatory bone destruction in mice, despite promoting osteoclastogenesis in the steady state.

    PubMed

    Nakayachi, Mai; Ito, Junta; Hayashida, Chiyomi; Ohyama, Yoko; Kakino, Akemi; Okayasu, Mari; Sato, Takuya; Ogasawara, Toru; Kaneda, Toshio; Suda, Naoto; Sawamura, Tatsuya; Hakeda, Yoshiyuki

    2015-06-01

    Inflammatory bone diseases have been attributed to increased bone resorption by augmented and activated bone-resorbing osteoclasts in response to inflammation. Although the production of diverse proinflammatory cytokines is induced at the inflamed sites, the inflammation also generates reactive oxygen species that modify many biological compounds, including lipids. Among the oxidized low-density lipoprotein (LDL) receptors, lectin-like oxidized LDL receptor-1 (LOX-1), which is a key molecule in the pathogenesis of multifactorial inflammatory atherosclerosis, was downregulated with osteoclast differentiation. Here, we demonstrate that LOX-1 negatively regulates osteoclast differentiation by basically suppressing the cell-cell fusion of preosteoclasts. The LOX-1-deleted (LOX-1(-/-)) mice consistently decreased the trabecular bone mass because of elevated bone resorption during the growing phase. In contrast, when the calvaria was inflamed by a local lipopolysaccharide-injection, the inflammation-induced bone destruction accompanied by the elevated expression of osteoclastogenesis-related genes was reduced by LOX-1 deficiency. Moreover, the expression of receptor activator of NF-κB ligand (RANKL), a trigger molecule for osteoclast differentiation, evoked by the inflammation was also abrogated in the LOX-1(-/-) mice. Osteoblasts, the major producers of RANKL, also expressed LOX-1 in response to proinflammatory agents, interleukin-1β and prostaglandin E2. In the co-culture of LOX-1(-/-) osteoblasts and wild-type osteoclast precursors, the osteoclastogenesis induced by interleukin-1β and prostaglandin E2 decreased; this process occurred in parallel with the downregulation of osteoblastic RANKL expression. Collectively, LOX-1 abrogation results in resistance to inflammatory bone destruction, despite promoting osteoclastogenesis in the steady state. Our findings indicate the novel involvement of LOX-1 in physiological bone homeostasis and inflammatory bone diseases.

  3. Low density microcellular foams

    DOEpatents

    Aubert, J.H.; Clough, R.L.; Curro, J.G.; Quintana, C.A.; Russick, E.M.; Shaw, M.T.

    1985-10-02

    Low density, microporous polymer foams are provided by a process which comprises forming a solution of polymer and a suitable solvent followed by rapid cooling of the solution to form a phase-separated system and freeze the phase-separated system. The phase-separated system comprises a polymer phase and a solvent phase, each of which is substantially continuous within the other. The morphology of the polymer phase prior to and subsequent to freezing determine the morphology of the resultant foam. Both isotropic and anisotropic foams can be produced. If isotropic foams are produced, the polymer and solvent are tailored such that the solution spontaneously phase-separates prior to the point at which any component freezes. The morphology of the resultant polymer phase determines the morphology of the reusltant foam and the morphology of the polymer phase is retained by cooling the system at a rate sufficient to freeze one or both components of the system before a change in morphology can occur. Anisotropic foams are produced by forming a solution of polymer and solvent that will not phase separate prior to freezing of one or both components of the solution. In such a process, the solvent typically freezes before phase separation occurs. The morphology of the resultant frozen two-phase system determines the morphology of the resultant foam. The process involves subjecting the solution to essentially one-dimensional cooling. Foams having a density of less than 0.1 g/cc and a uniform cell size of less than 10 ..mu..m and a volume such that the foams have a length greater than 1 cm are provided.

  4. Low density microcellular foams

    DOEpatents

    Aubert, James H.; Clough, Roger L.; Curro, John G.; Quintana, Carlos A.; Russick, Edward M.; Shaw, Montgomery T.

    1987-01-01

    Low density, microporous polymer foams are provided by a process which comprises forming a solution of polymer and a suitable solvent followed by rapid cooling of the solution to form a phase-separated system and freeze the phase-separated system. The phase-separated system comprises a polymer phase and a solvent phase, each of which is substantially continuous within the other. The morphology of the polymer phase prior to and subsequent to freezing determine the morphology of the resultant foam. Both isotropic and anisotropic foams can be produced. If isotropic foams are produced, the polymer and solvent are tailored such that the solution spontaneously phase-separates prior to the point at which any component freezes. The morphology of the resultant polymer phase determines the morphology of the resultant foam and the morphology of the polymer phase is retained by cooling the system at a rate sufficient to freeze one or both components of the system before a change in morphology can occur. Anisotropic foams are produced by forming a solution of polymer and solvent that will not phase separate prior to freezing of one or both components of the solution. In such a process, the solvent typically freezes before phase separation occurs. The morphology of the resultant frozen two-phase system determines the morphology of the resultant foam. The process involves subjecting the solution to essentially one-dimensional cooling. Means for subjecting such a solvent to one-dimensional cooling are also provided. Foams having a density of less than 0.1 g/cc and a uniform cell size of less than 10 .mu.m and a volume such that the foams have a length greater than 1 cm are provided.

  5. Human Serum Amyloid A3 (SAA3) Protein, Expressed as a Fusion Protein with SAA2, Binds the Oxidized Low Density Lipoprotein Receptor

    PubMed Central

    Tomita, Takeshi; Ieguchi, Katsuaki; Sawamura, Tatsuya; Maru, Yoshiro

    2015-01-01

    Serum amyloid A3 (SAA3) possesses characteristics distinct from the other serum amyloid A isoforms, SAA1, SAA2, and SAA4. High density lipoprotein contains the latter three isoforms, but not SAA3. The expression of mouse SAA3 (mSAA3) is known to be up-regulated extrahepatically in inflammatory responses, and acts as an endogenous ligand for the toll-like receptor 4/MD-2 complex. We previously reported that mSAA3 plays an important role in facilitating tumor metastasis by attracting circulating tumor cells and enhancing hyperpermeability in the lungs. On the other hand, human SAA3 (hSAA3) has long been regarded as a pseudogene, which is in contrast to the abundant expression levels of the other isoforms. Although the nucleotide sequence of hSAA3 is very similar to that of the other SAAs, a single oligonucleotide insertion in exon 2 causes a frame-shift to generate a unique amino acid sequence. In the present study, we identified that hSAA3 was transcribed in the hSAA2-SAA3 fusion transcripts of several human cell lines. In the fusion transcript, hSAA2 exon 3 was connected to hSAA3 exon 1 or hSAA3 exon 2, located approximately 130kb downstream from hSAA2 exon 3 in the genome, which suggested that it is produced by alternative splicing. Furthermore, we succeeded in detecting and isolating hSAA3 protein for the first time by an immunoprecipitation-enzyme linked immune assay system using monoclonal and polyclonal antibodies that recognize the hSAA3 unique amino acid sequence. We also demonstrated that hSAA3 bound oxidized low density lipoprotein receptor (oxLDL receptor, LOX-1) and elevated the phosphorylation of ERK, the intracellular MAP-kinase signaling protein. PMID:25738827

  6. Elevated levels of oxidized low-density lipoprotein correlate positively with C-reactive protein in patients with acute coronary syndrome.

    PubMed

    Zhang, Ya-chen; Wei, Jing-jing; Wang, Fei; Chen, Man-tian; Zhang, Mao-zhen

    2012-03-01

    The relationship between oxidized low-density lipoprotein (Ox-LDL) and C-reactive protein (CRP) in patients with acute coronary syndrome (ACS) is unknown. We, therefore, measured serum levels of Ox-LDL and high-sensitivity (hs)-CRP in 90 ACS patients, 45 stable angina pectoris (SAP) patients, and 66 healthy controls using sandwich ELISA. ACS patients were subdivided into: (1) acute myocardial infarction (AMI; n = 45); (2) unstable angina pectoris (UAP; n = 45) groups. In AMI patients, Ox-LDL (177.5 mmol/l) and hs-CRP (25.40 mg/l) levels were significantly higher (P < 0.01) than in UAP (Ox-LDL:107.5 mmol/l, hs-CRP:10.7 mg/l) and SAP (Ox-LDL:82.3 mmol/l, hs-CRP:2.10 mg/l) patients as well as controls (Ox-LDL:41.4 mmol/l, hs-CRP:1.76 mg/l). Ox-LDL/hs-CRP levels in UAP patients were significantly higher (P < 0.01) than in SAP patients and controls. Importantly, a positive correlation was found between Ox-LDL and CRP (r = 0.622; P < 0.01) levels. Serum levels of total, HDL, and LDL cholesterol did not differ among these patient groups. In conclusion, our data show that Ox-LDL and hs-CRP levels correlate positively in ACS patients, supporting the hypothesis that Ox-LDL and CRP may play a direct role in promoting the inflammatory component of atherosclerosis in these individuals. We suggest that Ox-LDL/CRP elevated levels may serve as markers of the severity of the disease in evaluation and management of ACS patients.

  7. The Effects of Phellinus linteus Polysaccharide Extracts on Cholesterol Efflux in Oxidized Low-Density Lipoprotein-Loaded THP-1 Macrophages.

    PubMed

    Li, Xiao-hui; Li, Yan; Cheng, Zhao-yun; Cai, Xi-guo; Wang, Hong-min

    2015-06-01

    The removal of excess cellular cholesterol is critical for maintaining cellular cholesterol homeostasis. Phellinus linteus polysaccharide extracts (PLPEs) is an immunomudulatory agent with a molecular weight of 153 kd. Here, we analyzed the effects of PLPEs on cholesterol efflux in oxidized low-density lipoprotein (ox-LDL)-loaded THP-1 (human acute monocytic leukemia cell line) macrophages. Various concentrations of PLPEs (5, 10, 20, and 100 μg/mL) were used to treat cells. Cholesterol efflux analysis was performed to analyze the cholesterol efflux ratio in PLPE-treated cells. Semiquantitative reverse transcription-polymerase chain reaction and Western blot analysis were conducted to assess the expression of target genes. Low dose of PLPEs (5-20 μg/mL) dose dependently enhanced cholesterol efflux to apolipoprotein A-I (ApoA-I), evidenced by promoting the expression of adenosine 5'-triphosphate (ATP)-binding cassette A1, ATP-binding cassette G1, and peroxisome proliferation-activated receptor γ, key regulators for cholesterol efflux. Moreover, GW9662, a potent antagonist of peroxisome proliferation-activated receptor γ, inhibited PLPE (20 μg/mL)-promoted cholesterol efflux to ApoA-I in a dose-dependent fashion. However, high dose of PLPEs (100 μg/mL) inhibited cholesterol efflux to ApoA-I from ox-LDL-loaded THP-1 macrophages, enhanced the production of superoxide anion, decreased mitochondrial membrane potential and ATP levels, and raised nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate oxidase subunits. Thus, these results indicate that low and high doses of PLPEs exhibit opposite effects on cholesterol efflux from ox-LDL-loaded THP-1 cells.

  8. Highly stable, fluorescence-labeled heptapeptides substituted with a D-amino acid for the specific detection of oxidized low-density lipoprotein in plasma.

    PubMed

    Sato, Akira; Yamanaka, Hikaru; Oe, Keitaro; Yokoyama, Izumi; Yamazaki, Yoji; Ebina, Keiichi

    2015-03-01

    Probes that can detect oxidized low-density lipoprotein (ox-LDL) in plasma and in atherosclerotic plaques can be useful for the diagnosis, prevention, and treatment of atherosclerosis. Recently, we have reported that two heptapeptides (Lys-Trp-Tyr-Lys-Asp-Gly-Asp, KP6) coupled to fluorescein isothiocyanate (FITC) through the ε-amino group of N-terminus Lys in the absence/presence of 6-amino-n-caproic acid (AC) linker to FITC-(FITC)KP6 and (FITC-AC)KP6-can be useful as fluorescent probes for the specific detection of ox-LDL. In this study, to develop the fluorescent peptides with high plasma stability for the specific detection of ox-LDL, we investigated the interaction of (FITC)KP6 and (FITC-AC)KP6 substituted with D-Lys at the N-terminus-(FITC)dKP6 and (FITC-AC)dKP6-with ox-LDL, and the in vitro stability of these peptides in mouse plasma. (FITC)dKP6 and (FITC-AC)dKP6 bound with high specificity to ox-LDL in a dose-dependent manner, and also to ox-LDL in the mouse plasma. Furthermore, (FITC)dKP6 was more stable than (FITC)KP6 in mouse plasma (102.1% versus 69.0% remained after 1 h). These findings strongly suggest that (FITC)dKP6 and (FITC-AC)dKP6 may be effective fluorescent probes with higher plasma stability than (FITC)KP6 and (FITC-AC)KP6 for the specific detection of ox-LDL.

  9. Oxidized low-density lipoprotein and C-reactive protein have combined utility for better predicting prognosis after acute coronary syndrome.

    PubMed

    Zhang, Ya-chen; Tang, Yong; Chen, Yu; Huang, Xiao-hong; Zhang, Min; Chen, Jian; Sun, Ying-gang; Li, Yi-gang

    2014-03-01

    It has been shown that the elevated concentrations of oxidized low-density lipoprotein (Ox-LDL) or high-sensitivity C-reactive protein (hs-CRP) are predictive of future cardiovascular events for acute coronary syndrome (ACS) patients. But, the combined value of Ox-LDL and hs-CRP for predicting cardiovascular events is still unknown. Serum concentrations of Ox-LDL, hs-CRP, and cTnT were measured in a prospective cohort of 425 selective ACS patients followed 3-5 years for the occurrence of acute myocardial infarction (AMI) or death (AMI/death). Among 425 enrolled patients, 124 patients demonstrated AMI/death. Baseline levels of Ox-LDL, hs-CRP, and cTnT were significantly higher in AMI/death group than the event-free survival group. Kaplan-Meier survival analyses supported that elevations in Ox-LDL or hs-CRP predicted increased cardiovascular events risks. However, the strongest risk prediction was achieved by assessing Ox-LDL and hs-CRP together. Patients with high levels of Ox-LDL and hs-CRP were more likely to experience AMI or death than those with either Ox-LDL or hs-CRP elevated. Receiver-operating characteristic curves showed that Ox-LDL and hs-CRP have higher sensitivity and specificity than those of cTnT for predicting AMI or death. This was reflected by the AUC values for Ox-LDL, hs-CRP, and cTnT, which were 0.891, 0.834, and 0.626, respectively. The combined use of Ox-LDL and hs-CRP may improve prognosis after ACS with high-sensitivity and specificity.

  10. Microarray analysis of ox-LDL (oxidized low-density lipoprotein)-regulated genes in human coronary artery smooth muscle cells.

    PubMed

    Minta, Joe; Jungwon Yun, James; St Bernard, Rosanne

    2010-01-01

    Recent studies suggest that circulating LDL (low-density lipoproteins) play a central role in the pathogenesis of atherosclerosis, and the oxidized form (ox-LDL) is highly atherogenic. Deposits of ox-LDL have been found in atherosclerotic plaques, and ox-LDL has been shown to promote monocyte recruitment, foam cell formation and the transition of quiescent and contractile vascular SMCs (smooth muscle cells) to the migratory and proliferative phenotype. SMC phenotype transition and hyperplasia are the pivotal events in the pathogenesis of atherosclerosis. To comprehend the complex molecular mechanisms involved in ox-LDL-mediated SMC phenotype transition, we have compared the differential gene expression profiles of cultured quiescent human coronary artery SMCs with cells induced with ox-LDL for 3 and 21 h using Affymetrix HG-133UA cDNA microarray chips. Assignment of the regulated genes into functional groups indicated that several genes involved in metabolism, membrane transport, cell-cell interactions, signal transduction, transcription, translation, cell migration, proliferation and apoptosis were differentially expressed. Our data suggests that the interaction of ox-LDL with its cognate receptors on SMCs modulates the induction of several growth factors and cytokines, which activate a variety of intracellular signalling mechanisms (including PI3K, MAPK, Jak/STAT, sphingosine, Rho kinase pathways) that contribute to SMC transition from the quiescent and contractile phenotype to the proliferative and migratory phenotype. Our study has also identified several genes (including CDC27, cyclin A1, cyclin G2, glypican 1, MINOR, p15 and apolipoprotein) not previously implicated in ox-LDL-induced SMC phenotype transition and substantially extends the list of potential candidate genes involved in atherogenesis.

  11. Oxidized low-density lipoprotein is a common risk factor for cardiovascular diseases and gastroenterological cancers via epigenomical regulation of microRNA-210

    PubMed Central

    Chen, Ku-Chung; Liao, Yi-Chu; Wang, Jaw-Yuan; Lin, Ying-Chu; Chen, Chung-Ho; Juo, Suh-Hang Hank

    2015-01-01

    Hyperlipidemia, including the oxidized low-density lipoprotein (oxLDL) accumulation, is a risk and highly associated with the development of cancers and cardiovascular diseases. microRNA-210 (miR-210), a hypoxia-responsive microRNA regulated by HIF-1α, has been implicated in cancer and cardiovascular disease formation. Furthermore, Bioinformatics analysis revealed that the promoter of the miR-210 gene contains CpG-rich regions. It is unclear whether miR-210 expression could be epigenetically regulated in these disease progresses. The study aimed to explore the relationships between lipid and miR-210 in the context of cardiovascular disease and gastrointestinal cancer. We demonstrated oxLDL can decrease methylation in the miR-210 promoter to up-regulate miR-210. HIF-1α can bind to miR-210 promoter, but this HIF-1α binding site can be blocked by methylation. We showed that subjects of carotid atherosclerosis, stroke patients and cancer patients had hypomethylation in the miR-210 promoter, especially the HIF-1α binding site. Furthermore, miR-210 can directly inhibit sprouty-related EVH1 domain 2 (SPRED2) expressions, and SPRED2 reduces cell migration via ERK/c-Fos/MMPs pathways. Increased miR-210 and reduced SPRED2 levels were found in aorta of mice under high-fat diet and tumor tissues, which implied that miR-210 can be an underlying mechanism to explain oxLDL as a common risk factor for cardiovascular disease and gastrointestinal cancer. PMID:26254226

  12. High plasma levels of oxidatively modified low-density lipoproteins are associated with the suppressed expression of immunomodulatory molecules in patients with hematological malignancies

    PubMed Central

    YANG, HAI-QING; QIU, FA-QI; JIN, KE; JIANG, NENG-GANG; ZHANG, LI

    2015-01-01

    Dyslipidemia is a common feature in immunosuppressed patients, such as kidney and bone marrow transplantation recipients and patients with breast, prostate or gynecological carcinoma or acute lymphoblastic leukemia. In addition, high levels of oxidatively modified low-density lipoproteins (oxLDLs) are closely associated with carcinogenesis. There are, however, no reports on the association between the serum oxLDL levels and the expression of important immunomodulatory molecules in patients with hematological disorders. In the present study, 39 patients with hematological disorders were stratified into four groups: Two groups with malignancies [chronic myeloid leukemia (CML) and acute myeloblastic leukemia (AML)] and two groups without malignancies [myelodysplastic syndrome (MDS) and iron deficiency anemia (IDA)]. Immunomodulatory molecules were monitored in these groups. The enzyme-linked immunosorbent assay results indicated that the plasma oxLDL levels were significantly higher in patients with AML or CML than those in patients with MDS or IDA. The quantitative polymerase chain reaction results revealed that the expression of numerous important immunomodulatory elements, including tumor-related genes, immunological and inflammatory cytokines, defense-responsive genes, genes regulating cell proliferation, adhesion and migration molecules and leukocyte chemotaxis genes, showed considerable variation in patients with hematological disorders, particularly in those with MDS or IDA, as compared with the expression in the healthy volunteers. The present study demonstrated that, in patients with a hematological malignancy (either AML or CML), the activation of numerous immune response-related molecules was inhibited. Thus, an association between hematological malignancies and dyslipidemia, i.e. high levels of oxLDL, is suggested. Further research is necessary to investigate how oxLDL influences cancer progression. PMID:26136994

  13. Oxidized low-density lipoprotein is a common risk factor for cardiovascular diseases and gastroenterological cancers via epigenomical regulation of microRNA-210.

    PubMed

    Chen, Ku-Chung; Liao, Yi-Chu; Wang, Jaw-Yuan; Lin, Ying-Chu; Chen, Chung-Ho; Juo, Suh-Hang Hank

    2015-09-15

    Hyperlipidemia, including the oxidized low-density lipoprotein (oxLDL) accumulation, is a risk and highly associated with the development of cancers and cardiovascular diseases. microRNA-210 (miR-210), a hypoxia-responsive microRNA regulated by HIF-1α, has been implicated in cancer and cardiovascular disease formation. Furthermore, Bioinformatics analysis revealed that the promoter of the miR-210 gene contains CpG-rich regions. It is unclear whether miR-210 expression could be epigenetically regulated in these disease progresses. The study aimed to explore the relationships between lipid and miR-210 in the context of cardiovascular disease and gastrointestinal cancer. We demonstrated oxLDL can decrease methylation in the miR-210 promoter to up-regulate miR-210. HIF-1α can bind to miR-210 promoter, but this HIF-1α binding site can be blocked by methylation. We showed that subjects of carotid atherosclerosis, stroke patients and cancer patients had hypomethylation in the miR-210 promoter, especially the HIF-1α binding site. Furthermore, miR-210 can directly inhibit sprouty-related EVH1 domain 2 (SPRED2) expressions, and SPRED2 reduces cell migration via ERK/c-Fos/MMPs pathways. Increased miR-210 and reduced SPRED2 levels were found in aorta of mice under high-fat diet and tumor tissues, which implied that miR-210 can be an underlying mechanism to explain oxLDL as a common risk factor for cardiovascular disease and gastrointestinal cancer. PMID:26254226

  14. Usefulness of Antibodies to Oxidized Low-Density Lipoproteins as Predictors of Morbidity and Prognosis in Heart Failure Patients Aged ≥65 Years.

    PubMed

    Charach, Gideon; Michowitz, Yoav; Rogowski, Ori; Charach, Lior; Argov, Ori; George, Jacob; Grosskopf, Itamar

    2015-11-01

    Elevated level of antibodies to oxidized low-density lipoproteins (OxLDL-Ab) was shown to reliably predict morbidity and mortality in patients with heart failure (HF). Two hundred and eleven patients aged ≥65 years treated at the Heart Failure Unit, Tel Aviv-Sourasky Medical Center, were included in this retrospective study. The end points were time to the first hospitalization (morbidity), all-cause mortality, and a combination of the two (composite outcome). HF duration ranged from 8 to 10.5 years. Mean follow-up was 5.2 ± 1.9 years. The mean number of clinical visits was 18.3 ± 2.4. Participants were divided according to OxLDL-Ab level. Group 1 had Ox LDL-Ab level <200 arbitrary U/ml. Group 2 had OxLDL-Ab level ≥200 arbitrary U/ml. The mean time to the first hospitalization was 25.8 ± 17.0 months. The mortality rate was 44.1%. Combined mortality and hospitalization rate was 58.8%. Adjusted hazard ratios of OxLDL-Ab for hospitalization were 3.16, p <0.001, 95% confidence interval 1.740 to 5.736 and for composite outcome 2.67, p <0.001, 95% confidence interval 1.580 to 4.518. In conclusion, OxLDL-Ab level was the best predictor for both hospitalization and composite outcome. It may, thus, serve as a useful clue for early and more accurate detection of poorly controlled HF and as a marker for imminent exacerbations of thereof. PMID:26372212

  15. A novel murine model for non-alcoholic steatohepatitis developed by combination of a high-fat diet and oxidized low-density lipoprotein.

    PubMed

    Yimin; Furumaki, Hiroaki; Matsuoka, Shiho; Sakurai, Toshihiro; Kohanawa, Masashi; Zhao, Songji; Kuge, Yuji; Tamaki, Nagara; Chiba, Hitoshi

    2012-02-01

    Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome that is characterized by steatosis, inflammation, and fibrosis, and may progress to cirrhosis and carcinoma. To investigate its pathogenic processes, we established a novel murine model for NASH by combination of a high-fat diet (HFD) and oxidized low-density lipoprotein (oxLDL). Mice that received HFD for 23 weeks showed hepatic steatosis, slight fibrosis, and a high level of lipid peroxidation compared with a regular diet (RD)-fed mice. Hepatic injury and elevated tumor necrosis factor (TNF)-α mRNA expression were also detected in these mice. Moreover, oxLDL administration to HFD-fed mice during weeks 21-23 not only aggravated hepatic steatosis, fibrosis, and lipid metabolism, but also resulted in intense inflammation, including severe hepatic injury and inflammatory cell infiltration, which are the typical histological features of NASH. Inflammation was accompanied by increased gene expression of TNF-α and interleukin (IL)-6. Additionally, the livers of RD-fed animals treated with oxLDL during weeks 21-23 were characterized by foamy macrophages and inflammatory cell infiltration along with an elevated IL-6 mRNA level. These results suggest that an increased oxidative state, including HFD-induced intracellular lipid peroxidation and its extracellular source from oxLDL, is the actual trigger for hepatic inflammation in which liver injury is mediated by TNF-α and inflammatory cell accumulation is dependent on IL-6. HFD and oxLDL also induced insulin resistance in mice; additionally, oxLDL downregulated insulin secretion. In this model, CD36 overexpression was observed in the hepatocytes of HFD-fed mice and those treated with HFD and oxLDL, and in the hepatic macrophages of RD-fed mice immediately after oxLDL treatment. In vitro experiments indicated a rapid and transient elevation of CD36 on macrophage plasma membrane in response to oxLDL. Our findings demonstrate that CD36

  16. Why are low-density lipoproteins atherogenic?

    PubMed Central

    Young, S G; Parthasarathy, S

    1994-01-01

    Low-density lipoproteins (LDLs) carry most of the cholesterol in human plasma, and high levels of LDL cholesterol clearly cause heart disease. In recent years, many scientists have focused on elucidating the pathophysiologic steps that lie between elevated levels of LDL in the plasma and atherosclerotic plaques in the arterial wall. A large number of scientific studies indicate that oxidation of LDL within the arterial wall may be an important early step in atherogenesis. The uptake of oxidized LDL by macrophages is a likely explanation for the formation of macrophage foam cells in early atherosclerotic lesions. In addition, oxidized LDL has many other potentially proatherogenic properties. Images PMID:8160466

  17. Cyclic tensile stretch load and oxidized low density lipoprotein synergistically induce lectin-like oxidized ldl receptor-1 in cultured bovine chondrocytes, resulting in decreased cell viability and proteoglycan synthesis.

    PubMed

    Akagi, Masao; Nishimura, Shunji; Yoshida, Kohji; Kakinuma, Takumi; Sawamura, Tatsuya; Munakata, Hiroshi; Hamanishi, Chiaki

    2006-08-01

    Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 microg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/- 3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan synthesis [81.0% +/- 7.1% and 85.7% +/- 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% +/- 4.6% for native-LDL (n = 3)]. Cyclic loading and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/- 6.7% of control at 24 h, respectively (n = 3; p < 0.01 when compared with individual application of cyclic loading or 10 microg/mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis.

  18. Low density metal hydride foams

    DOEpatents

    Maienschein, Jon L.; Barry, Patrick E.

    1991-01-01

    Disclosed is a low density foam having a porosity of from 0 to 98% and a density less than about 0.67 gm/cc, prepared by heating a mixture of powered lithium hydride and beryllium hydride in an inert atmosphere at a temperature ranging from about 455 to about 490 K for a period of time sufficient to cause foaming of said mixture, and cooling the foam thus produced. Also disclosed is the process of making the foam.

  19. Comparative studies on the antioxidant activities of nine common food legumes against copper-induced human low-density lipoprotein oxidation in vitro.

    PubMed

    Xu, B J; Yuan, S H; Chang, S K C

    2007-09-01

    Epidemiological studies demonstrated that the consumption of dietary antioxidant was associated with the prevention of atherosclerosis. The aim of this study was to investigate the antioxidant activities of the hydrophilic extracts from 9 selected legumes based on copper-induced human LDL oxidation model in vitro. The antioxidant activities were assessed on the basis of the formation of conjugated dienes (lag time of oxidation) and thiobarbituric acid reactive substances (TBARS) as the early and later stage markers of LDL oxidation. The results showed that the extracts of black beans (Phaseolus vulgaris L.), lentils (Lens culinaris), black soybeans (Glycine max), and red kidney beans (Phaseolus vulgaris L.) had significant (P < 0.05) longer LDL oxidation lag times (128.8, 124.2, 107.7, and 111.1 min, respectively) than the LDL control group (94.9 min). No significant lag-time lengthening was observed in other tested legume extracts. On the other hand, black beans, lentils, black soybeans, red kidney beans, and pinto beans exhibited higher antioxidant capacities (Trolox equivalents) than yellow peas, green peas, chickpea, and yellow soybeans in both LDL-conjugated dienes assay and LDL-TBARS assay. Meanwhile, the antioxidant activities of these legumes against LDL-lipid peroxidation in the above assays were found to correlate very significantly (P < 0.01) with their phenolic substances, and DPPH radical scavenging activity and ORAC (oxygen radical absorbance capacity). These results suggest that consuming black beans, lentils, black soybeans, and red kidney beans may have potential in preventing the development of atherosclerosis from the perspective of inhibiting LDL oxidation.

  20. Comparative studies on the antioxidant activities of nine common food legumes against copper-induced human low-density lipoprotein oxidation in vitro.

    PubMed

    Xu, B J; Yuan, S H; Chang, S K C

    2007-09-01

    Epidemiological studies demonstrated that the consumption of dietary antioxidant was associated with the prevention of atherosclerosis. The aim of this study was to investigate the antioxidant activities of the hydrophilic extracts from 9 selected legumes based on copper-induced human LDL oxidation model in vitro. The antioxidant activities were assessed on the basis of the formation of conjugated dienes (lag time of oxidation) and thiobarbituric acid reactive substances (TBARS) as the early and later stage markers of LDL oxidation. The results showed that the extracts of black beans (Phaseolus vulgaris L.), lentils (Lens culinaris), black soybeans (Glycine max), and red kidney beans (Phaseolus vulgaris L.) had significant (P < 0.05) longer LDL oxidation lag times (128.8, 124.2, 107.7, and 111.1 min, respectively) than the LDL control group (94.9 min). No significant lag-time lengthening was observed in other tested legume extracts. On the other hand, black beans, lentils, black soybeans, red kidney beans, and pinto beans exhibited higher antioxidant capacities (Trolox equivalents) than yellow peas, green peas, chickpea, and yellow soybeans in both LDL-conjugated dienes assay and LDL-TBARS assay. Meanwhile, the antioxidant activities of these legumes against LDL-lipid peroxidation in the above assays were found to correlate very significantly (P < 0.01) with their phenolic substances, and DPPH radical scavenging activity and ORAC (oxygen radical absorbance capacity). These results suggest that consuming black beans, lentils, black soybeans, and red kidney beans may have potential in preventing the development of atherosclerosis from the perspective of inhibiting LDL oxidation. PMID:17995667

  1. Lemon grass (Cymbopogon citratus (D.C) Stapf) polyphenols protect human umbilical vein endothelial cell (HUVECs) from oxidative damage induced by high glucose, hydrogen peroxide and oxidised low-density lipoprotein.

    PubMed

    Campos, J; Schmeda-Hirschmann, G; Leiva, E; Guzmán, L; Orrego, R; Fernández, P; González, M; Radojkovic, C; Zuñiga, F A; Lamperti, L; Pastene, E; Aguayo, C

    2014-05-15

    The aromatic herb Cymbopogon citratus Stapf is widely used in tropical and subtropical countries in cooking, as a herbal tea, and in traditional medicine for hypertension and diabetes. Some of its properties have been associated with the in vitro antioxidant effect of polyphenols isolated from their aerial parts. However, little is known about C. citratus effects on endothelial cells oxidative injury. Using chromatographic procedures, a polyphenol-rich fraction was obtained from C. citratus (CCF) and their antioxidant properties were assessed by cooper-induced LDL oxidation assay. The main constituents of the active CCF, identified by high-performance liquid chromatography with diode-array detection and mass spectrometry (HPLC-DAD-MS), were chlorogenic acid, isoorientin and swertiajaponin. CCF 10 and 100 μg/ml diminishes reactive oxidative species (ROS) production in human umbilical vein endothelial cell (HUVECs), challenged with high D-glucose (60% inhibition), hydrogen peroxide (80% inhibition) or oxidised low-density lipoprotein (55% inhibition). CCF 10 or 100 μg/ml did not change nitric oxide (NO) production. However, CCF was able to inhibit vasoconstriction induced by the thromboxane A2 receptor agonist U46619, which suggest a NO-independent vasodilatador effect on blood vessels. Our results suggest that lemon grass antioxidant properties might prevent endothelial dysfunction associated to an oxidative imbalance promoted by different oxidative stimuli.

  2. Low-density ionization behavior

    SciTech Connect

    Baker, G.A. Jr.

    1995-04-01

    As part of a continuing study of the physics of matter under extreme conditions, I give some results on matter at extremely low density. In particular I compare a quantum mechanical calculation of the pressure for atomic hydrogen with the corresponding pressure given by Thomas-Fermi theory. (This calculation differs from the ``confined atom`` approximation in a physically significant way.) Since Thomas-Fermi theory in some sense, represents the case of infinite nuclear charge, these cases should represent extremes. Comparison is also made with Saha theory, which considers ionization from a chemical point of view, but is weak on excited-state effects. In this theory, the pressure undergoes rapid variation as electron ionization levels are passed. This effect is in contrast to the smooth behavior of the Thomas-Fermi fixed temperature, complete ionization occurs in the low density limit, I study the case where the temperature goes appropriately to zero with the density. Although considerable modification is required, Saha theory is closer to the actual results for this case than is Thomas-Fermi theory.

  3. Evidence for an additional intracellular site of action of probucol in the prevention of oxidative modification of low density lipoprotein. Use of a new water-soluble probucol derivative.

    PubMed Central

    Parthasarathy, S

    1992-01-01

    Oxidative modification of low density lipoprotein (LDL) renders it more atherogenic. Probucol, a highly nonpolar antioxidant, is transported in lipoproteins, including LDL, and inhibits oxidative modification of LDL in vitro. The ability of probucol to inhibit atherogenesis in the LDL receptor-deficient rabbit has been attributed to its antioxidant effect. We report synthesis of a new water-soluble analogue of probucol that is very effective in preventing cell-induced LDL oxidation. The polar probucol derivative, diglutaryl probucol, is efficiently taken up by endothelial cells and macrophages in culture and is hydrolyzed to release the active antioxidant, probucol. The treated cells, after thorough washing, show a marked decrease in their capacity to oxidize LDL during a subsequent incubation. At high concentrations of the derivative, the cells also released free probucol into the medium. Thus, the effectiveness of probucol in vivo may be related both to its presence in LDL, acting as a nonspecific antioxidant, and to an additional ability to inhibit cell-mediated oxidation of LDL by virtue of its uptake into cells. PMID:1569200

  4. Oxidized low-density lipoprotein attenuated desmoglein 1 and desmocollin 2 expression via LOX-1/Ca(2+)/PKC-β signal in human umbilical vein endothelial cells.

    PubMed

    Li, Yuan-Bin; Zhang, Qing-Hai; Chen, Zhuang; He, Zhi-Jun; Yi, Guang-Hui

    Numerous studies have reported the presence of oxidized LDL (ox-LDL) and expression of its lectin-like receptor, LOX-1, have been shown in atherosclerotic regions. The present study aims to investigate the effects of ox-LDL on expression of desmoglein 1 (DSG1) and desmocollin 2 (DSC2) in endothelial cells, and to explore the role of LOX-1 mediated signal in the permeability injury associated with DSG1 and DSC2 disruption induced by oxidized lipoprotein. RT-PCR and Western blotting were applied to determine the mRNA and protein expression levels of DSG1 and DSC2 in human umbilical vein endothelial cells (HUVECs) respectively. Immunoreactivities of DSG1 and DSC2 were detected by laser scanning confocal microscope (LSCM). HUVEC monolayers permeability was evaluated by FITC-labeled LDL in transwell assay system. The possible signal was assessed using in vitro blocking LOX-1 or Ca(2+) channel or PKC. The DSG1 and DSC2 expression were decreased by ox-LDL in concentration- and time-dependent manner. The effects of ox-LDL were mediated by its endothelial receptor, LOX-1. In parallel experiments, ox-LDL increased the influx of extracellular calcium, activation of protein kinase C (PKC) and permeability to LDL, which was inhibited by the LOX-1blocking antibody (10 μg/ml), Ca(2+) channel blocker (Diltiazem, 50 μmol/L) and PKC-β inhibitor (hispidin, 4 μmol/L). These results suggested that ox-LDL-induced decrease in DSG1 and DSC2 expression and monolayer barrier injury via calcium uptake and PKC-β activation following up-regulation of LOX-1 is one of the mechanisms of inducing greater permeability in HUVECs. PMID:26498522

  5. Oxidized low-density lipoprotein attenuated desmoglein 1 and desmocollin 2 expression via LOX-1/Ca(2+)/PKC-β signal in human umbilical vein endothelial cells.

    PubMed

    Li, Yuan-Bin; Zhang, Qing-Hai; Chen, Zhuang; He, Zhi-Jun; Yi, Guang-Hui

    Numerous studies have reported the presence of oxidized LDL (ox-LDL) and expression of its lectin-like receptor, LOX-1, have been shown in atherosclerotic regions. The present study aims to investigate the effects of ox-LDL on expression of desmoglein 1 (DSG1) and desmocollin 2 (DSC2) in endothelial cells, and to explore the role of LOX-1 mediated signal in the permeability injury associated with DSG1 and DSC2 disruption induced by oxidized lipoprotein. RT-PCR and Western blotting were applied to determine the mRNA and protein expression levels of DSG1 and DSC2 in human umbilical vein endothelial cells (HUVECs) respectively. Immunoreactivities of DSG1 and DSC2 were detected by laser scanning confocal microscope (LSCM). HUVEC monolayers permeability was evaluated by FITC-labeled LDL in transwell assay system. The possible signal was assessed using in vitro blocking LOX-1 or Ca(2+) channel or PKC. The DSG1 and DSC2 expression were decreased by ox-LDL in concentration- and time-dependent manner. The effects of ox-LDL were mediated by its endothelial receptor, LOX-1. In parallel experiments, ox-LDL increased the influx of extracellular calcium, activation of protein kinase C (PKC) and permeability to LDL, which was inhibited by the LOX-1blocking antibody (10 μg/ml), Ca(2+) channel blocker (Diltiazem, 50 μmol/L) and PKC-β inhibitor (hispidin, 4 μmol/L). These results suggested that ox-LDL-induced decrease in DSG1 and DSC2 expression and monolayer barrier injury via calcium uptake and PKC-β activation following up-regulation of LOX-1 is one of the mechanisms of inducing greater permeability in HUVECs.

  6. Oxidized low-density lipoprotein and lipoprotein(a) levels in chronic kidney disease patients under hemodialysis: influence of adiponectin and of a polymorphism in the apolipoprotein(a) gene.

    PubMed

    Ribeiro, Sandra; Faria, Maria do Sameiro; Silva, Gil; Nascimento, Henrique; Rocha-Pereira, Petronila; Miranda, Vasco; Vieira, Emília; Santos, Rosário; Mendonça, Denisa; Quintanilha, Alexandre; Costa, Elísio; Belo, Luís; Santos-Silva, Alice

    2012-10-01

    Chronic kidney disease (CKD) has been associated with an abnormal lipid profile. Our aim was to study the interplay between oxidized low-density lipoprotein (ox-LDL), adiponectin, and blood lipids and lipoproteins in Portuguese patients with CKD under hemodialysis (HD); the influence of the pentanucleotide repeat polymorphism in the apolipoprotein(a) (apo [a]) gene upon lipoprotein(a) (Lp[a]) levels in these patients. We studied 187 HD patients and 25 healthy individuals. ox-LDL and adiponectin were measured using enzyme-linked immunoassays. Apo(a) genotyping was performed by polymerase chain reaction, followed by electrophoresis in polyacrylamide gel. Compared with controls, patients presented with significantly higher levels of adiponectin, Lp(a), and ox-LDL/low-density lipoprotein cholesterol (LDLc) ratio; significantly lower levels of total cholesterol (TC), LDLc, apo A-I, apo B, ox-LDL, and TC/high-density lipoprotein cholesterol (HDLc) ratio were also observed. Similar changes were observed for patients with or without statin therapy, as compared with controls, except for Lp(a). Multiple linear regression analysis showed that body mass index, HDLc, time on HD, and triglycerides (TG) were independent determinants of adiponectin levels, and that apo B, TG and LDLc were independent determinants of ox-LDL concentration. Concerning the apo(a) genotype, the homozygous (TTTTA)8/8 repeats was the most prevalent (50.8%). A raised proportion of LDL particles that are oxidized was observed. Adiponectin almost doubled its values in patients and seems to be an important determinant in HDLc and TG levels, improving the lipid profile in these patients. Apo(a) alleles with a lower number of repetitions are more frequent in patients with higher Lp(a).

  7. A Subregion of Reelin Suppresses Lipoprotein-Induced Cholesterol Accumulation in Macrophages

    PubMed Central

    Guo, Zhongmao; Yang, Fang; Smith, Carlie; Yang, Hong

    2015-01-01

    Activation of apolipoprotein E receptor-2 (apoER2) and very low density lipoprotein receptor (VLDLR) inhibits foam cell formation. Reelin is a ligand of these receptors. Here we generated two reelin subregions containing the receptor binding domain with or without its C-terminal region (R5-6C and R5-6, respectively) and studied the impact of these peptides on macrophage cholesterol metabolism. We found that both R5-6C and R5-6 can be secreted by cells. Purified R5-6 protein can bind apoER2 and VLDLR. Overexpression of apoER2 in macrophages increased the amount of R5-6 bound to the cell surface. Treatment of macrophages with 0.2 μg/ml R5-6 elevated ATP binding cassette A1 (ABCA1) protein level by ~72% and apoAI-mediated cholesterol efflux by ~39%. In addition, the medium harvested from cells overexpressing R5-6 or R5-6C (R5-6- and R5-6C-conditioned media, respectively) also up-regulated ABCA1 protein expression, which was associated with accelerated cholesterol efflux and enhanced phosphorylation of phosphatidylinositol 3 kinase (PI3K) and specificity protein-1 (Sp1) in macrophages. The increased ABCA1 expression and cholesterol efflux by R5-6- and R5-6C-conditioned media were diminished by Sp1 or PI3K inhibitors mithramycin A and LY294002. Further, the cholesterol accumulation induced by apoB-containing, apoE-free lipoproteins was significantly less in macrophages incubated with R5-6- or R5-6C-conditioned medium than in those incubated with control conditioned medium. Knockdown of apoER2 or VLDLR attenuated the inhibitory role of R5-6-conditioned medium against lipoprotein-induced cholesterol accumulation. These results suggest that the reelin subregion R5-6 can serve as a tool for studying the role of apoER2 and VLDLR in atherogenesis. PMID:26317415

  8. The relationship between concentrations of magnesium and oxidized low-density lipoprotein and Beta2-microglobulin in the serum of patients on the end-stage of renal disease.

    PubMed

    Raikou, Vaia D; Kyriaki, Despina

    2016-05-01

    The end-stage of renal disease is associated with increased oxidative stress and oxidative modification of low-density lipoproteins (LDLs). Beta2 microglobulin (beta2M) is accumulated in the serum of dialysis patients. Magnesium (Mg) plays a protective role in the development of oxidative stress in healthy subjects. We studied the relationship between concentrations of magnesium and oxidized LDL (ox-LDL) and beta2M in the serum of patients on the end stage of renal disease. In 96 patients on on-line- predilution hemodiafiltration, beta2M and intact parathormone were measured by radioimmunoassays. High-sensitivity C-reactive protein (hsCRP) and ox-LDL were measured using ΕLISA. Serum bicarbonate levels were measured in the blood gas analyser gas machine. We performed logistic regression analysis models to investigate Mg as an important independent predictor of elevated ox-LDL and high beta2M serum concentrations, after adjustment to traditional and specific for dialysis patients' factors. We observed a positive correlation of Mg with ox-LDL (r = 0.383, P = 0.001), but the association of Mg with beta2M, hsCRP, and serum bicarbonate levels was significantly inverse (r = -0.252, P = 0.01, r = -0.292, P = 0.004, and r = -0.282, P = 0.04 respectively). The built logistic-regression analysis showed that Mg act as a significant independent factor for the elevated ox-LDL and beta2M serum concentrations adjusting to traditional and specific factors for these patients. We observed a positive relationship between magnesium and acidosis status- related ox-LDL concentrations, but the inverse association between magnesium and beta2M serum concentrations in hemodialysis patients.

  9. The relationship between concentrations of magnesium and oxidized low-density lipoprotein and Beta2-microglobulin in the serum of patients on the end-stage of renal disease.

    PubMed

    Raikou, Vaia D; Kyriaki, Despina

    2016-05-01

    The end-stage of renal disease is associated with increased oxidative stress and oxidative modification of low-density lipoproteins (LDLs). Beta2 microglobulin (beta2M) is accumulated in the serum of dialysis patients. Magnesium (Mg) plays a protective role in the development of oxidative stress in healthy subjects. We studied the relationship between concentrations of magnesium and oxidized LDL (ox-LDL) and beta2M in the serum of patients on the end stage of renal disease. In 96 patients on on-line- predilution hemodiafiltration, beta2M and intact parathormone were measured by radioimmunoassays. High-sensitivity C-reactive protein (hsCRP) and ox-LDL were measured using ΕLISA. Serum bicarbonate levels were measured in the blood gas analyser gas machine. We performed logistic regression analysis models to investigate Mg as an important independent predictor of elevated ox-LDL and high beta2M serum concentrations, after adjustment to traditional and specific for dialysis patients' factors. We observed a positive correlation of Mg with ox-LDL (r = 0.383, P = 0.001), but the association of Mg with beta2M, hsCRP, and serum bicarbonate levels was significantly inverse (r = -0.252, P = 0.01, r = -0.292, P = 0.004, and r = -0.282, P = 0.04 respectively). The built logistic-regression analysis showed that Mg act as a significant independent factor for the elevated ox-LDL and beta2M serum concentrations adjusting to traditional and specific factors for these patients. We observed a positive relationship between magnesium and acidosis status- related ox-LDL concentrations, but the inverse association between magnesium and beta2M serum concentrations in hemodialysis patients. PMID:27215248

  10. The 94- to 97-kDa mouse macrophage membrane protein that recognizes oxidized low density lipoprotein and phosphatidylserine-rich liposomes is identical to macrosialin, the mouse homologue of human CD68.

    PubMed Central

    Ramprasad, M P; Fischer, W; Witztum, J L; Sambrano, G R; Quehenberger, O; Steinberg, D

    1995-01-01

    We have previously reported the partial purification of a 94- to 97-kDa plasma membrane protein from mouse peritoneal macrophages that binds oxidatively modified low density lipoprotein (OxLDL) and phosphatidylserine-rich liposomes. We have now identified that protein as macrosialin, a previously cloned macrophage-restricted membrane protein in the lysosomal-associated membrane protein family (mouse homologue of human CD68). Early in the course of purification of the 94- to 97-kDa protein, a new OxLDL-binding band at 190-200 kDa appeared and copurified with the 94- to 97-kDa protein. The HPLC pattern of tryptic peptides from this higher molecular mass ligand-binding band closely matched that derived from the 94- to 97-kDa band. Specifically, the same three macrosialin-derived tryptic peptides (9, 9, and 15 residues) were present in the purified 94- to 97-kDa band and in the 190- to 200-kDa band and antisera raised against peptide sequences in macrosialin recognized both bands. An antiserum against macrosialin precipitated most of the 94- to 97-kDa OxLDL-binding material. We conclude that the binding of OxLDL to mouse macrophage membranes is in part attributable to macrosialin. Our previous studies show that OxLDL competes with oxidized red blood cells and with apoptotic thymocytes for binding to mouse peritoneal macrophages. Whether macrosialin plays a role in recognition of OxLDL and oxidatively damaged cells by intact macrophages remains uncertain. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7568176

  11. Method of synthesizing a low density material

    DOEpatents

    Lorensen, L.E.; Monaco, S.B.

    1987-02-27

    A novel method of synthesizing a polymeric material of low density of the order of 50mg/cc or less. Such a low density material has applications in many areas including laser target fabrication. The method comprises preparing a polymer blend of two incompatible polymers as a major and a minor phase by mixing them and extruding the mixture, and then selectively extracting the major component, to yield a fine, low density structure.

  12. A Phytochemical-rich Multivitamin-multimineral Supplement Is Bioavailable and Reduces Serum Oxidized Low-density Lipoprotein, Myeloperoxidase, and Plasminogen Activator Inhibitor-1 in a Four-week Pilot trial of Healthy Individuals

    PubMed Central

    Desai, Anuradha; Lamb, Joseph J.; Chang, Jyh-Lurn; Darland, Gary; Konda, Veera R.

    2014-01-01

    Background: A multivitamin-multimineral supplement combined with a diverse blend of bioactive phytochemicals may provide additional antioxidant capacity and anti-inflammatory property for overall health. This convenient feature may be useful for individuals who want to increase their intake of phytochemicals. Methods: We conducted a pilot study in 15 healthy individuals (8 women and 7 men, mean age 41.7±14.9 years, mean body mass index 28.0±5.6) to investigate the effects of this novel formulation on biomarkers associated with oxidative stress and inflammation. After a 2-week diet that limited intake of fruits and vegetables to 2 servings/day, participants continued with the same restricted diet but began consuming 2 tablets of the study product for the subsequent 4 weeks. Fasting blood samples collected at Week 2 and Week 6 were analyzed and compared using paired t-tests for levels of carotenoids, folate, vitamin B12, homocysteine, oxidized low-density lipoprotein cholesterol (oxLDL), high-sensitivity C-reactive protein (hs-CRP), F2-isoprostane, plasminogen activator inhibitor-1 (PAI-1), and myeloperoxidase. Noninvasive peripheral arterial tonometry (EndoPAT) was also measured. Results: After 4 weeks of supplementation, plasma levels of carotenoids, folate, and vitamin B12, but not homocysteine, were significantly increased (P<.05). Serum levels of oxLDL, PAI-1 and myeloperoxidase were significantly reduced (P<.05), but F2-isoprostane, hs-CRP, and EndoPAT measures were unchanged compared with baseline. The study product was well tolerated. Conclusions: This nutritional supplement is bioavailable as indicated by the significant increase in plasma carotenoids, vitamin B12, and folate levels and may provide health benefits by significantly reducing serum levels of oxLDL, myeloperoxidase, and PAI-1 in healthy individuals. PMID:24808980

  13. [Atherogenic modification of low-density lipoproteins].

    PubMed

    Sukhorukov, V N; Karagodin, V P; Orekhov, A N

    2016-05-01

    One of the first manifestations of atherosclerosis is accumulation of extra- and intracellular cholesterol esters in the arterial intima. Formation of foam cells is considered as a trigger in the pathogenesis of atherosclerosis. Low density lipoprotein (LDL) circulating in human blood is the source of lipids accumulated in the arterial walls. This review considered features and role in atherogenesis different modified forms of LDL: oxidized, small dense, electronegative and especially desialylated LDL. Desialylated LDL of human blood plasma is capable to induce lipid accumulation in cultured cells and it is atherogenic. LDL possesses numerous alterations of protein, carbohydrate and lipid moieties and therefore can be termed multiple-modified LDL. Multiple modification of LDL occurs in human blood plasma and represents a cascade of successive changes in the lipoprotein particle: desialylation, loss of lipids, reduction in the particle size, increase of surface electronegative charge, etc. In addition to intracellular lipid accumulation, stimulatory effects of naturally occurring multiple-modified LDL on other processes involved in the development of atherosclerotic lesions, namely cell proliferation and fibrosis, were shown. PMID:27562992

  14. Cilostazol prevents remnant lipoprotein particle-induced monocyte adhesion to endothelial cells by suppression of adhesion molecules and monocyte chemoattractant protein-1 expression via lectin-like receptor for oxidized low-density lipoprotein receptor activation.

    PubMed

    Park, So Youn; Lee, Jeong Hyun; Kim, Yong Ki; Kim, Chi Dae; Rhim, Byung Yong; Lee, Won Suk; Hong, Ki Whan

    2005-03-01

    This study shows cilostazol effect to prevent remnant lipoprotein particle (RLP)-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). Upon incubation of HUVECs with RLP (50 microg/ml), adherent monocytes significantly increased by 3.3-fold with increased cell surface expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, E-selectin, and monocyte chemoattractant protein-1 (MCP-1). Cilostazol ( approximately 1-100 microM) concentration dependently repressed these variables as did (E)3-[(4-t-butylphenyl)sulfonyl]-2-propenenitrile (BAY 11-7085) (10 microM), a specific nuclear factor-kappaB (NF-kappaB) inhibitor. Cilostazol effects were significantly antagonized by iberiotoxin (1 microM), a maxi-K channel blocker. RLP significantly increased expression of lectin-like receptor for oxidized low-density lipoprotein (LDL) (LOX-1) receptor protein. Upon transfection with antisense LOX-1 oligodeoxynucleotide (As-LOX-1), LOX-1 receptor expression was reduced, whereas HUVECs with sense LOX-1 oligodeoxynucleotide did express high LOX-1 receptor. RLP-stimulated superoxide and tumor necrosis factor-alpha levels were significantly lowered with decreased expression of VCAM-1 and MCP-1 by transfection with As-LOX-1 as did polyinosinic acid (10 microg/ml, a LOX-1 receptor inhibitor). RLP significantly degraded inhibitory kappaBalpha in the cytoplasm and activated nuclear factor-kappaB (NF-kappaB) p65 in the nucleus of HUVECs with increased luciferase activity of NF-kappaB, all of which were reversed by cilostazol (10 microM), BAY 11-7085, and polyinosinic acid. Together, cilostazol suppresses RLP-stimulated increased monocyte adhesion to HUVECs by suppression of LOX-1 receptor-coupled NF-kappaB-dependent nuclear transcription via mediation of the maxi-K channel opening.

  15. Increases in oxidized low-density lipoprotein and other inflammatory and adhesion molecules with a concomitant decrease in high-density lipoprotein in the individuals exposed to arsenic in Bangladesh.

    PubMed

    Karim, Md Rezaul; Rahman, Mashiur; Islam, Khairul; Mamun, Abdullah Al; Hossain, Shakhawoat; Hossain, Ekhtear; Aziz, Abdul; Yeasmin, Fouzia; Agarwal, Smita; Hossain, Md Imam; Saud, Zahangir Alam; Nikkon, Farjana; Hossain, Mostaque; Mandal, Abul; Jenkins, Richard O; Haris, Parvez I; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled

    2013-09-01

    Elevated exposure to arsenic has been suggested to be associated with atherosclerosis leading to cardiovascular disease (CVD). However, biochemical events underlying the arsenic-induced atherosclerosis have not yet been fully documented. The aim of this study was to investigate the associations of circulating molecules involved in atherosclerosis with arsenic exposure in the individuals exposed to arsenic in Bangladesh. A total of 324 study subjects, 218 from arsenic-endemic areas and 106 from nonendemic areas in Bangladesh, were recruited. Drinking water, hair, nail, and blood samples were collected from the study subjects for analysis. Total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels were lower in arsenic-endemic subjects than those of nonendemic subjects. Oxidized LDL (Ox-LDL), C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) levels were significantly higher in arsenic-endemic subjects than those in nonendemic subjects. All these circulating molecules showed significant correlations with arsenic exposure (water, hair, and nail arsenic concentrations), and all these relations were significant before and after adjusting for relevant covariates. Among the circulating molecules tested in this study, HDL, Ox-LDL, and CRP showed dose-response relationships with arsenic exposure. Ox-LDL/HDL ratios were increased with the increasing concentrations of arsenic in the water, hair, and nails. Furthermore, non-HDL cholesterol and TC/HDL ratios were significantly correlated with arsenic exposure before and after adjusting for relevant covariates. Thus, all the observed associations may be the major features of arsenic exposure-related atherosclerosis leading to CVD.

  16. Hydrogen sulfide suppresses oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 generation from macrophages via the nuclear factor κB (NF-κB) pathway.

    PubMed

    Du, Junbao; Huang, Yaqian; Yan, Hui; Zhang, Qiaoli; Zhao, Manman; Zhu, Mingzhu; Liu, Jia; Chen, Stella X; Bu, Dingfang; Tang, Chaoshu; Jin, Hongfang

    2014-04-01

    This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine-β-synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-κB and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in ox-LDL-induced macrophage inflammation.

  17. The terminal six amino-acids of the carboxy cytoplasmic tail of CD36 contain a functional domain implicated in the binding and capture of oxidized low-density lipoprotein.

    PubMed Central

    Malaud, Eric; Hourton, Delphine; Giroux, Louise Marie; Ninio, Ewa; Buckland, Robin; McGregor, John L

    2002-01-01

    CD36, a major adhesion molecule expressed by monocytes/macrophages, plays a key role in the binding and internalization of oxidized low-density lipoprotein (OxLDL). This adhesion molecule, a member of an important scavenger receptor family, contains a very short C-terminal cytoplasmic tail that is known to induce intracellular signalling events. However, the domains on the cytoplasmic tail involved in such signal transduction are unknown. In this study, we have investigated the functional components of the cytoplasmic tail by site-directed mutagenesis coupled with functional OxLDL and monoclonal antibody (mAb) binding studies. Seven truncated or punctual CD36 constructs, localized in the cytoplasmic tail, were produced by site-directed mutagenesis. Each construct was stably expressed in HEK293 cells. We used a quantitative and a qualitative method, labelling OxLDL with either iodine or rhodamine, to determine the functional importance of the cytoplasmic domains in OxLDL internalization. Results indicate that: (1) a deletion of the last amino-acid (construct K472STOP) significantly reduces, compared with wild-type, the binding, internalization and degradation of OxLDL; (2) truncation of the last six amino-acids (construct R467STOP) significantly reduces OxLDL binding; (3) the above two constructs (K472STOP and R467STOP) showed a reduced rate of OxLDL internalization compared with wild-type; (4) the binding and rate of internalization of an anti-CD36 monoclonal antibody (10/5) was not affected by the above mentioned mutants (K472STOP and R467STOP), compared with wild-type. This study shows, for the first time, a specific site on the CD36 cytoplasmic tail that is critical for the binding, endocytosis and targeting of OxLDL. PMID:12023894

  18. Hydrogen Sulfide Suppresses Oxidized Low-density Lipoprotein (Ox-LDL)-stimulated Monocyte Chemoattractant Protein 1 generation from Macrophages via the Nuclear Factor κB (NF-κB) Pathway*

    PubMed Central

    Du, Junbao; Huang, Yaqian; Yan, Hui; Zhang, Qiaoli; Zhao, Manman; Zhu, Mingzhu; Liu, Jia; Chen, Stella X.; Bu, Dingfang; Tang, Chaoshu; Jin, Hongfang

    2014-01-01

    This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine-β-synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-κB and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in ox-LDL-induced macrophage inflammation. PMID:24550391

  19. Clinical association of baseline levels of conjugated dienes in low-density lipoprotein and nitric oxide with aggressive B-cell non-Hodgkin lymphoma and their relationship with immunoglobulins and Th1-to-Th2 ratio

    PubMed Central

    Haddouche, Mustapha; Meziane, Warda; Hadjidj, Zeyneb; Mesli, Naima; Aribi, Mourad

    2016-01-01

    Objective The aim of this study was to highlight the clinical association of baseline levels of conjugated dienes in low-density lipoprotein (LDL-BCD) and nitric oxide (NO) with immunoglobulins (Igs) and T helper (Th)1/Th2 ratio in patients with newly diagnosed B-cell non-Hodgkin lymphoma (NHL). Patients and methods Thirty-two newly diagnosed patients with aggressive B-cell NHL and 25 age-, sex-, and body-mass-index-matched healthy controls were randomly selected for a cross-sectional case–control study conducted at the Hematology Department of Tlemcen Medical Centre University (northwest of Algeria). Results Circulating levels of LDL-BCD and NO and those of IgA and IgM were significantly higher in patients than in controls. The levels of Th1/Th2 ratio and plasma total antioxidant capacity were significantly lower in patients compared with controls, while malondialdehyde and protein carbonyl levels were significantly higher in patients. B-cell NHL was significantly associated with high levels of LDL-BCD from 25th to 75th percentile (25th percentile: relative risk [RR] =2.26, 95% confidence interval [CI] 1.42–3.59, P=0.014; 50th percentile: RR =2.84, 95% CI 1.72–4.68, P<0.001; 75th percentile: RR =5.43, 95% CI 2.58–11.42, P<0.001). Similarly, the disease was significantly associated with high levels of NO production from 25th to 75th percentile (25th percentile: RR =2.07, 95% CI 1.25–3.44, P=0.024; 50th percentile: RR =2.78, 95% CI 1.63–4.72, P<0.001; 75th percentile: RR =4.68, 95% CI 2.21–9.91, P<0.001). Moreover, LDL-BCD levels were positively and significantly correlated with interferon (IFN)-γ, whereas NO levels were inversely and significantly correlated with IFN-γ and Th1/Th2 ratio. Conclusion LDL-BCD and NO production seem to be associated with aggressive B-cell NHL and alteration of Th1/Th2 ratio. Our results have to be examined using ex vivo mechanistic studies leading to further investigations of these parameters, with an interest in the

  20. Low density, resorcinol-formaldehyde aerogels

    DOEpatents

    Pekala, R.W.

    1988-05-26

    The polycondensation of resorcinol with formaldehyde under alkaline conditions results in the formation of surface functionalized polymer ''clusters''. The covalent crosslinking of these ''clusters'' produces gels which when processed under supercritical conditions, produce low density, organic aerogels (density less than or equal to100 mg/cc; cell size less than or equal to0.1 microns). The aerogels are transparent,dark red in color and consist of interconnected colloidal-like particles with diameters of about 100 A/degree/. These aerogels may be further carbonized to form low density carbon foams with cell size of about 0.1 micron. 1 fig., 1 tab.

  1. Low density, resorcinol-formaldehyde aerogels

    DOEpatents

    Pekala, Richard W.

    1989-01-01

    The polycondensation of resorcinol with formaldehyde under alkaline conditions results in the formation of surface functionalized polymer "clusters". The covalent crosslinking of these "clusters" produces gels which when processed under supercritical conditions, produce low density, organic aerogels (density .ltoreq.100 mg/cc; cell size .ltoreq.0.1 microns). The aerogels are transparent, dark red in color and consist of interconnected colloidal-like particles with diameters of about 100 .ANG.. These aerogels may be further carbonized to form low density carbon foams with cell size of about 0.1 micron.

  2. Low density, resorcinol-formaldehyde aerogels

    DOEpatents

    Pekala, R.W.

    1989-10-10

    The polycondensation of resorcinol with formaldehyde under alkaline conditions results in the formation of surface functionalized polymer clusters. The covalent crosslinking of these clusters produces gels which when processed under supercritical conditions, produce low density, organic aerogels (density [<=]100 mg/cc; cell size [<=]0.1 microns). The aerogels are transparent, dark red in color and consist of interconnected colloidal-like particles with diameters of about 100 [angstrom]. These aerogels may be further carbonized to form low density carbon foams with cell size of about 0.1 micron.

  3. Low density, resorcinol-formaldehyde aerogels

    DOEpatents

    Pekala, Richard W.

    1991-01-01

    The polycondensation of resorcinol with formaldehyde under alkaline conditions results in the formation of surface functionalized polymer "Clusters". The covalent crosslinking of these "clusters" produces gels which when processed under supercritical conditions, produce low density, organic aerogels (density.ltoreq.100 mg/cc; cell size .ltoreq.0.1 microns). The aerogels are transparent, dark red in color and consist of interconnected colloidal-like particles with diameters of about 100.circle.. These aerogels may be further carbonized to form low density carbon foams with cell size of about 0.1 micron.

  4. Study of low density air transportation concepts

    NASA Technical Reports Server (NTRS)

    Webb, H. M.

    1972-01-01

    Low density air transport refers to air service to sparsely populated regions. There are two major objectives. The first is to examine those characteristics of sparsely populated areas which pertain to air transportation. This involves determination of geographical, commercial and population trends, as well as those traveler characteristics which affect the viability of air transport in the region. The second objective is to analyze the technical, economic and operational characteristics of low density air service. Two representative, but diverse arenas, West Virginia and Arizona, were selected for analysis: The results indicate that Arizona can support air service under certain assumptions whereas West Virginia cannot.

  5. Role of low-density lipoprotein apheresis.

    PubMed

    Ziajka, Paul

    2005-08-22

    Low-density lipoprotein (LDL) apheresis has been shown to reduce plasma levels of total cholesterol, LDL cholesterol, and lipoprotein(a). In addition to these lipoprotein changes, LDL apheresis induces atherosclerosis regression, improves myocardial perfusion and endothelial function, and may reduce cardiovascular event rates. PMID:16098847

  6. Oxidized Lipoprotein as a Major Vessel Cell Proliferator in Oxidized Human Serum

    PubMed Central

    Noguchi, Noriko

    2016-01-01

    Oxidative stress is correlated with the incidence of several diseases such as atherosclerosis and cancer, and oxidized biomolecules have been determined as biomarkers of oxidative stress; however, the detailed molecular relationship between generated oxidation products and the promotion of diseases has not been fully elucidated. In the present study, to clarify the role of serum oxidation products in vessel cell proliferation, which is related to the incidence of atherosclerosis and cancer, the major vessel cell proliferator in oxidized human serum was investigated. Oxidized human serum was prepared by free radical exposure, separated using gel chromatography, and then each fraction was added to several kinds of vessel cells including endothelial cells and smooth muscle cells. It was found that a high molecular weight fraction in oxidized human serum specifically induced vessel cell proliferation. Oxidized lipids were contained in this high molecular weight fraction, while cell proliferation activity was not observed in oxidized lipoprotein-deficient serum. Oxidized low-density lipoproteins induced vessel cell proliferation in a concentration-dependent manner. Taken together, these results indicate that oxidized lipoproteins containing lipid oxidation products function as a major vessel cell proliferator in oxidized human serum. These findings strongly indicate the relevance of determination of oxidized lipoproteins and lipid oxidation products in the diagnosis of vessel cell proliferation-related diseases such as atherosclerosis and cancer. PMID:27483438

  7. Fabrication of low density ceramic material

    DOEpatents

    Meek, T.T.; Blake, R.D.; Sheinberg, H.

    1985-01-01

    A precursor mixture and a method of making a low-density ceramic structural material are disclosed. The precursor mixture includes hollow microballoons, typically made of glass, together with a cementing agent capable of being cured by microwave irradiation. A preferred cementing agent is liquid hydrated potassium silicate, which is mixed with the glass microballoons to form a slurry. Upon irradiation the potassium silicate is dehydrated to form a solid porous matrix in which the microballoons are evenly distributed. Ground glass or other filling agents may be included in the slurry to enhance the properties of the final product. Low-density structural ceramics having densities on the order of 0.1 to 0.3 are obtained.

  8. Shock compression of low-density foams

    SciTech Connect

    Holmes, N.C.

    1993-07-01

    Shock compression of very low density micro-cellular materials allows entirely new regimes of hot fluid states to be investigated experimentally. Using a two-stage light-gas gun to generate strong shocks, temperatures of several eV are readily achieved at densities of roughly 0.5--1 g/cm{sup 3} in large, uniform volumes. The conditions in these hot, expanded fluids are readily found using the Hugoniot jump conditions. We will briefly describe the basic methodology for sample preparation and experimental measurement of shock velocities. We present data for several materials over a range of initial densities. This paper will explore the applications of these methods for investigations of equations of state and phase diagrams, spectroscopy, and plasma physics. Finally, we discus the need for future work on these and related low-density materials.

  9. Low-Density, Sprayable, Thermal Insulation

    NASA Technical Reports Server (NTRS)

    Mclemore, James P.; Norton, William E.; Lambert, Joe D.; Simpson, William G.; Echols, Sherman; Sharpe, Max H.; Hill, William E.

    1989-01-01

    Improved formulation prevents cracks. Low-density, thermally insulating material applied by spraying it onto surface to be protected. Material, called "MSA-2" improved version of similar material called "MSA-1". Useful as sprayed, lightweight insulation to cover large areas in terrestrial applications in which manual attachment too slow or impractical. Formulated to be more flexible and to prevent coats as thick as 1/2 in. from developing stress cracks as they cure.

  10. Natural phenylpropanoids inhibit lipoprotein-induced endothelin-1 secretion by endothelial cells.

    PubMed

    Martin-Nizard, Françoise; Sahpaz, Sevser; Kandoussi, Abdelmejid; Carpentier, Marie; Fruchart, Jean-Charles; Duriez, Patrick; Bailleul, François

    2004-12-01

    There is increasing evidence that oxidized low-density lipoproteins (Ox-LDL) might be involved in the pathogenesis of atherosclerosis and it has been reported that polyphenols inhibit LDL peroxidation and atherosclerosis. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide isolated from endothelial cells and it induces smooth muscle cell proliferation. ET-1 secretion is increased in atheroma and induces deleterious effects such as vasospasm and atherosclerosis. The goal of this study was to test the effect of four natural phenolic compounds against copper-oxidized LDL (Cu-LDL)-induced ET-1 liberation by bovine aortic endothelial cells (BAEC). The tested compounds were phenylpropanoid glycosides previously isolated from the aerial parts of Marrubium vulgare L. (acteoside 1, forsythoside B 2, arenarioside 3 and ballotetroside 4). ET-1 secretion increased when cells were incubated with Cu-LDL but the compounds 1-4 inhibited this increase. These results were confirmed by quantitative-polymerase chain reaction (QPCR) analysis. Since ET-1 plays an important role in atherosclerosis development, our work suggests that the tested phenylpropanoids could have a beneficial effect in inhibiting atherosclerosis development. PMID:15563769

  11. A New Approach of Designing Superalloys for Low Density

    NASA Technical Reports Server (NTRS)

    MacKay, Rebecca A.; Gabb, Timothy P.; Smialek, James L.; Nathal, Michael V.

    2010-01-01

    New low-density single-crystal (LDS) alloy, have bee. developed for turbine blade applications, which have the potential for significant improvements in the thrust-to-weight ratio over current production superalloys. An innovative alloying strategy was wed to achieve alloy density reductions, high-temperature creep resistance, microstructural stability, and cyclic oxidation resistance. The alloy design relies on molybdenum as a potent. lower-density solid-solution strengthener in the nickel-based superalloy. Low alloy density was also achieved with modest rhenium levels tmd the absence of tungsten. Microstructural, physical mechanical, and environmental testing demonstrated the feasibility of this new LDS superalloy design.

  12. Relativistic Plasmas in Low Density Environments

    SciTech Connect

    Rudnick, Lawrence

    2009-12-18

    We have been developing techniques over the last several years to identify and study relativistic plasmas in low density environments. These relativistic plasmas may be the best or only available indicators of diffuse baryons in portions of the Warm-Hot Intergalactic Medium outside of rich galaxy clusters. Studying such faint radio synchrotron sources requires removal of confusion from both background radio galaxies and the foreground Milky Way. In these proceedings, we briefly summarize the techniques we are developing and some of our initial results. Our discoveries likely represent the ''tip of the iceberg'' to be exploited by the nascent generation of radio telescopes.

  13. Low density, microcellular foams, preparation, and articles

    DOEpatents

    Young, Ainslie T.; Marsters, Robert G.; Moreno, Dawn K.

    1984-01-01

    A microcellular low density foam of poly(4-methyl-1-pentene) which is particularly useful for forming targets for inertial confinement fusion has been developed. Articles made from the foam have been machined to tolerances of 0.0001 inch, although the densities of the fragile foam are low (about 10 to about 100 mg/cc) and the cell sizes are small (about 10 to about 30 .mu.m). Methods for forming the foam and articles are given; and the yield strength of the foam of the invention is higher than was obtained in other structures of this same material.

  14. Low density, microcellular foams, preparation, and articles

    DOEpatents

    Young, A.T.

    1982-03-03

    A microcellular low-density foam of poly(4-methyl-1-pentene) particularly useful for forming targets for inertial confinement fusion has been developed. Articles made from the foam have been machined to tolerances of 0.0001 inch, although the densities of the fragile foam are low (about 10 to about 100 mg/cc) and the cell sizes are small (about 10 to about 30 ..mu..m). Methods for forming the foam and articles are given. The yield strength of the foam of the invention is higher than was obtained in other structures of this same material.

  15. Split Hubbard bands at low densities

    NASA Astrophysics Data System (ADS)

    Hansen, Daniel; Perepelitsky, Edward; Shastry, B. Sriram

    2011-05-01

    We present a numerical scheme for the Hubbard model that throws light on the rather esoteric nature of the upper and lower Hubbard bands, which have been invoked often in literature. We present a self-consistent solution of the ladder-diagram equations for the Hubbard model, and show that these provide, at least in the limit of low densities of particles, a vivid picture of the Hubbard split bands. We also address the currently topical problem of decay of the doublon states that are measured in optical trap studies, using both the ladder scheme and also an exact two-particle calculation of a relevant Green’s function.

  16. Sprayable low density ablator and application process

    NASA Technical Reports Server (NTRS)

    Sharpe, M. H.; Hill, W. E.; Simpson, W. G.; Carter, J. M.; Brown, E. L.; King, H. M.; Schuerer, P. H.; Webb, D. D. (Inventor)

    1978-01-01

    A sprayable, low density ablative composition is described consisting esentially of: (1) 100 parts by weight of a mixture of 25-65% by weight of phenolic microballoons, 0-20% by weight of glass microballoons, 4-10% by weight of glass fibers, 25-45% by weight of an epoxy-modified polyurethane resin, 2-4% by weight of a bentonite dispersing aid, and 1-2% by weight of an alcohol activator for the bentonite; (2) 1-10 parts by weight of an aromatic amine curing agent; and (3) 200-400 parts by weight of a solvent.

  17. Synthesis of Low Density Metallic Nanowire Network

    NASA Astrophysics Data System (ADS)

    Burks, Edward; Flores, Chad; Gilbert, Dustin; Liu, Kai; Felter, Thomas; Charnvanichborikarn, Supakit; Kucheyev, Sergei; Colvin, Jeffery

    2013-03-01

    Highly porous metallic nanostructures have been shown to possess interesting thermal, electrical and mechanical properties due in part to their high surface areas and low densities. In this work, ion track-etched membranes were used as a template for electrodeposition to realize a low density interconnected copper nanowire network. Polycarbonate membranes (3-6 microns thick) were first irradiated with energetic Xe6+ ions at normal incidence and multiple 45 degree azimuthal angles. The total irradiation density was 2x109 tracks/cm2. Following a UV/ozone treatment, NaOH was used to preferentially etch the latent tracks of ion damage, creating intersecting nanopores in the polycarbonate matrix. A thin metal layer was then sputtered onto one side of the now-porous membrane to be used as a working electrode. Selected metals such as Cu and Co were then electrodeposited from a sulfate electrolyte into the pores, filling the membrane with an interconnected wire network. The polycarbonate membrane was then folded onto itself several times, and dichloromethane was used to dissolve away the polycarbonate. So far densities as low as 40mg/cm3 have been achieved. Structural and magnetic properties of such networks have been investigated. This work has been supported by DTRA #BRCALL08-Per3-C-2-0006, and in part by NSF DMR-1008791.

  18. Hydrogen crystallization in low-density aerogels.

    PubMed

    Kucheyev, S O; Van Cleve, E; Johnston, L T; Gammon, S A; Worsley, M A

    2015-04-01

    Crystallization of liquids confined in disordered low-density nanoporous scaffolds is poorly understood. Here, we use relaxation calorimetry to study the liquid-solid phase transition of H2 in a series of silica and carbon (nanotube- and graphene-based) aerogels with porosities ≳94%. Results show that freezing temperatures of H2 inside all the aerogels studied are depressed but do not follow predictions of the Gibbs-Thomson theory based on average pore diameters measured by conventional gas sorption techniques. Instead, we find that, for each material family investigated, the depression of average freezing temperatures scales linearly with the ratio of the internal surface area (measured by gas sorption) and the total pore volume derived from the density of aerogel monoliths. The slope of such linear dependences is, however, different for silica and carbon aerogels, which we attribute to microporosity of carbons and the presence of macropores in silica aerogels. Our results have important implications for the analysis of pore size distributions of low-density nanoporous materials and for controlling crystallization of fuel layers in targets for thermonuclear fusion energy applications. PMID:25781182

  19. Low Density Supersonic Decelerator Parachute Decelerator System

    NASA Technical Reports Server (NTRS)

    Gallon, John C.; Clark, Ian G.; Rivellini, Tommaso P.; Adams, Douglas S.; Witkowski, Allen

    2013-01-01

    The Low Density Supersonic Decelerator Project has undertaken the task of developing and testing a large supersonic ringsail parachute. The parachute under development is intended to provide mission planners more options for parachutes larger than the Mars Science Laboratory's 21.5m parachute. During its development, this new parachute will be taken through a series of tests in order to bring the parachute to a TRL-6 readiness level and make the technology available for future Mars missions. This effort is primarily focused on two tests, a subsonic structural verification test done at sea level atmospheric conditions and a supersonic flight behind a blunt body in low-density atmospheric conditions. The preferred method of deploying a parachute behind a decelerating blunt body robotic spacecraft in a supersonic flow-field is via mortar deployment. Due to the configuration constraints in the design of the test vehicle used in the supersonic testing it is not possible to perform a mortar deployment. As a result of this limitation an alternative deployment process using a ballute as a pilot is being developed. The intent in this alternate approach is to preserve the requisite features of a mortar deployment during canopy extraction in a supersonic flow. Doing so will allow future Mars missions to either choose to mortar deploy or pilot deploy the parachute that is being developed.

  20. Ideal magnetohydrodynamic interchanges in low density plasmas

    SciTech Connect

    Huang Yimin; Goel, Deepak; Hassam, A.B.

    2005-03-01

    The ideal magnetohydrodynamic equations are usually derived under the assumption V{sub A}<low density plasmas wherein V{sub A} can be comparable to or greater than c. This involves relaxation of the usual charge quasineutrality assumption and the inclusion of electromagnetic momentum on par with plasma momentum. The extended system is applied to interchange instabilities in 'line-tied' slab geometry as well as to centrifugally confined plasmas. It is found that interchange growth rates are reduced by a factor of 1+V{sub A}{sup 2}/c{sup 2}, corresponding to a larger effective mass resulting from the extra electromagnetic momentum. Line tying is unaffected.

  1. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions.

    PubMed Central

    Napoli, C; D'Armiento, F P; Mancini, F P; Postiglione, A; Witztum, J L; Palumbo, G; Palinski, W

    1997-01-01

    To determine whether oxidized LDL enhances atherogenesis by promoting monocyte recruitment into the vascular intima, we investigated whether LDL accumulation and oxidation precede intimal accumulation of monocytes in human fetal aortas (from spontaneous abortions and premature newborns who died within 12 h; fetal age 6.2+/-1.3 mo). For this purpose, a systematic assessment of fatty streak formation was carried out in fetal aortas from normocholesterolemic mothers (n = 22), hypercholesterolemic mothers (n = 33), and mothers who were hypercholesterolemic only during pregnancy (n = 27). Fetal plasma cholesterol levels showed a strong inverse correlation with fetal age (R = -0.88, P < 0.0001). In fetuses younger than 6 mo, fetal plasma cholesterol levels correlated with maternal ones (R = 0.86, P = 0.001), whereas in older fetuses no such correlation existed. Fetal aortas from hypercholesterolemic mothers and mothers with temporary hypercholesterolemia contained significantly more and larger lesions (758,651+/-87,449 and 451,255+/-37,448 micron2 per section, respectively; mean+/-SD) than aortas from normocholesterolemic mothers (61,862+/-9,555 micron2; P < 0.00005). Serial sections of the arch, thoracic, and abdominal aortas were immunostained for recognized markers of atherosclerosis: macrophages, apo B, and two different oxidation-specific epitopes (malondialdehyde- and 4-hydroxynonenal-lysine). Of the atherogenic sites that showed positive immunostaining for at least one of these markers, 58.6% were established lesions containing both macrophage/foam cells and oxidized LDL (OxLDL). 17.3% of all sites contained only native LDL, and 13.3% contained only OxLDL without monocyte/ macrophages. In contrast, only 4.3% of sites contained isolated monocytes in the absence of native or oxidized LDL. In addition, 6.3% of sites contained LDL and macrophages but few oxidation-specific epitopes. These results demonstrate that LDL oxidation and formation of fatty streaks occurs

  2. Neutrino oscillations in low density medium.

    PubMed

    Ioannisian, A N; Smirnov, A Y

    2004-12-10

    We have solved the evolution equation for neutrinos in a low density medium, Vnu(e), we have found the attenuation effect: a decrease of the sensitivity to remote structures, d>l(nu)E/DeltaE, where l(nu) is the oscillation length and DeltaE/E is the energy resolution of a detector.

  3. Low density gas dynamic wall boundary conditions

    NASA Technical Reports Server (NTRS)

    Collins, F. G.

    1986-01-01

    Low density nozzles or large expansion ratio nozzles used in space experience rarefaction effects near their exit in the form of velocity slip and temperature jump at the walls. In addition, the boundary layers become very thick and there is a very strong viscous/inviscid interaction. For these reasons no existing design technique has been found to accurately predict the nozzle flow properties up to the nozzle exit. The objective of this investigation was to examine the slip boundary conditions and formulate them in a form appropriate for use with a full Navier-Stokes numerical code. The viscous/inviscid interaction would automatically be accounted for by using a compressible Navier-Stokes code. Through examination of the interaction of molecules with solid surfaces, a model for the distribution function of the reflected molecules has been determined and this distribution function has been used to develop a new slip boundary condition that can be shown to yield more realistic surface boundary conditions.

  4. Kepler-79's low density planets

    SciTech Connect

    Jontof-Hutter, Daniel; Lissauer, Jack J.; Rowe, Jason F.; Fabrycky, Daniel C.

    2014-04-10

    Kepler-79 (KOI-152) has four planetary candidates ranging in size from 3.5 to 7 times the size of the Earth, in a compact configuration with orbital periods near a 1:2:4:6 chain of commensurability, from 13.5 to 81.1 days. All four planets exhibit transit timing variations with periods that are consistent with the distance of each planet to resonance with its neighbors. We perform a dynamical analysis of the system based on transit timing measurements over 1282 days of Kepler photometry. Stellar parameters are obtained using a combination of spectral classification and the stellar density constraints provided by light curve analysis and orbital eccentricity solutions from our dynamical study. Our models provide tight bounds on the masses of all four transiting bodies, demonstrating that they are planets and that they orbit the same star. All four of Kepler-79's transiting planets have low densities given their sizes, which is consistent with other studies of compact multiplanet transiting systems. The largest of the four, Kepler-79 d (KOI-152.01), has the lowest bulk density yet determined among sub-Saturn mass planets.

  5. Radiance Measurement for Low Density Mars Entry

    NASA Technical Reports Server (NTRS)

    Cruden, Brett A.

    2012-01-01

    We report measurements of radiance behind a shock wave in Martian simulant (96% CO2, 4% N2) atmosphere at conditions relevant for aerodynamic decelerators. Shock waves are generated in the NASA Ames Electric Arc Shock Tube (EAST) facility at velocities from 6-8 km/s and freestream densities from 1.2-5.9 x 10(exp -4) kilograms per cubic meter (0.05-0.25 Torr, corresponding to 35-50 km altitude). Absolute radiance is measured as a function of wavelength and position in the shock. Radiance measurements extend from the vacuum ultraviolet to near infrared (120-1650 nm). As at higher density/velocity, radiation is dominate by CO 4th positive radiation in the vacuum ultraviolet, though CN contribution is also significant. At most low density conditions, the shock does not relax to equilibrium over several centimeters. A small number of measurements in the mid-infrared were performed to quantify radiation from the fundamental vibrational transition in CO, and this is found to be a minor contributor to the overall radiance at these speeds. Efforts to extend test time and reliability in the 60 cm (24) shock tube will be discussed in the full paper.

  6. Systems evaluation of low density air transportation concepts

    NASA Technical Reports Server (NTRS)

    Bruce, R. W.; Webb, H. M.

    1972-01-01

    Methods were studied for improving air transportation to low-density population regions in the U.S. through the application of new aeronautical technology. The low-density air service concepts are developed for selected regions, and critical technologies that presently limit the effective application of low-density air transportation systems are identified.

  7. Charge properties of low density lipoprotein subclasses.

    PubMed

    La Belle, M; Blanche, P J; Krauss, R M

    1997-04-01

    Measurements of electrophoretic mobility and particle size of low density lipoproteins (LDL) allowed use of standard electrokinetic theory to quantitate LDL charge characteristics from subjects with predominance of large LDL (pattern A, n = 9) or small LDL (pattern B, n = 8). Pattern A LDL was found to have significantly lower (P < or = 0.001) mobility (-0.22 +/- 0.01 micron s-1 cm V-1), surface potential (-4.2 +/- 0.3 mV) and charge density (-500 +/- 34 esu/cm2) than pattern B LDL (-0.25 +/- 0.01 micron s-1 cm V-1, -4.9 +/- 0.3 mV, and -580 +/- 30 esu/cm2), but no significant difference in particle valence (-22.0 +/- 1.4 for pattern A vs. -21.8 +/- 1.9 for pattern B). Thus, the greater mobility of pattern B LDL is due to similar net charge residing on a smaller particle. Comparison of subfractions in pattern B relative to pattern A LDL revealed greater surface potential in all pattern B subfractions and greater charge density in fractions of d > or = 1.032 g/ml. In a subset of subjects incubation with neuraminidase produced significant reductions in all LDL charge parameters for all subfractions, but did not abolish the differences between pattern A and B. Thus increased surface potential and charge density of unfractionated pattern B LDL is due both to charge properties of particles across the size and density spectrum as well as enrichment of pattern B LDL with smaller, denser particles that have higher surface charge density.

  8. Study on ternary low density polyethylene/linear low density polyethylene/thermoplastic starch blend films.

    PubMed

    Sabetzadeh, Maryam; Bagheri, Rouhollah; Masoomi, Mahmood

    2015-03-30

    In this work, low-density polyethylene/linear low-density polyethylene/thermoplastic starch (LDPE/LLDPE/TPS) films are prepared with the aim of obtaining environmentally friendly materials containing high TPS content with required packaging properties. Blending of LDPE/LLDPE (70/30 wt/wt) with 5-20 wt% of TPS and 3 wt% of PE-grafted maleic anhydride (PE-g-MA) is performed in a twin-screw extruder, followed by the blowing process. Differential scanning calorimetric results indicate starch has more pronounced effect on crystallization of LLDPE than LDPE. Scanning electron micrograph shows a fairly good dispersion of TPS in PE matrices. Fourier transfer infrared spectra confirm compatibility between polymers using PE-g-MA as the compatibilizer. Storage modulus, loss modulus and complex viscosity increase with incorporation of starch. Tensile strength and elongation-at-break decrease from 18 to 10.5 MPa and 340 to 200%, respectively when TPS increases from 5 to 20%. However, the required mechanical properties for packaging applications are attained when 15 wt% starch is added, as specified in ASTM D4635. Finally 12% increase in water uptake is achieved with inclusion of 15 wt% starch.

  9. Dense low density lipoproteins and coronary artery disease.

    PubMed

    Krauss, R M

    1995-02-23

    A common, genetically influenced lipoprotein subclass profile characterized by a predominance of small, dense low density lipoprotein (LDL) particles is associated with relative increases in plasma triglyceride and apolipoprotein (apo) B-100, and reduced levels of high density lipoprotein cholesterol and apoAI. Recently, this phenotype has also been associated with the insulin resistance syndrome and familial combined hyperlipidemia. Case-control studies of patients with myocardial infarction and angiographically documented coronary artery disease (CAD) have demonstrated that 40-50% of patients have the small, dense LDL phenotype and that this is associated with a 2- to 3-fold increase in disease risk. However, because of strong statistical correlations among the multiple features of the phenotype, it has been difficult to determine whether > or = 1 of its metabolic alterations are primarily responsible for increased CAD susceptibility. More direct evidence for enhanced atherogenicity of lipoproteins in this trait derives from a recent report that LDL-cholesterol lowering by diet and drug treatment resulted in reduced coronary angiographic progression in CAD subjects with predominantly dense LDL, but that an equivalent lowering of LDL cholesterol in subjects with more buoyant LDL was not associated with angiographic benefit. Further, in vitro findings have indicated increased susceptibility of small, dense LDL to oxidative modification and relatively greater binding of these particles to arterial wall proteoglycans. Thus, the small, dense LDL trait may underlie familial predisposition to CAD in a large proportion of the population, and its presence may indicate the potential for benefit from specific therapeutic interventions.

  10. Observation of ionization fronts in low density foam targets

    SciTech Connect

    Hoarty, D. |; Willi, O.; Barringer, L.; Vickers, C.; Watt, R.; Nazarov, W.

    1999-05-01

    Ionization fronts have been observed in low density chlorinated foam targets and low density foams confined in gold tubes using time resolved {ital K}-shell absorption spectroscopy. The front was driven by an intense pulse of soft x-rays produced by high power laser irradiation. The density and temperature profiles inferred from the radiographs provided detailed measurement of the conditions. The experimental data were compared to radiation hydrodynamics simulations and reasonable agreement was obtained. {copyright} {ital 1999 American Institute of Physics.}

  11. Hemodynamics alter arterial low-density lipoprotein metabolism

    SciTech Connect

    Warty, V.S.; Calvo, W.J.; Berceli, S.A.; Pham, S.M.; Durham, S.J.; Tanksale, S.K.; Klein, E.C.; Herman, I.M.; Borovetz, H.S. )

    1989-10-01

    We have investigated the role of hemodynamic factors on low-density lipoprotein transport and metabolism in the intact arterial wall. Freshly excised canine carotid blood vessels were exposed to well-defined pulsatile flow in vitro for continuous periods up to 20 hours. We chose to impose the following hemodynamic conditions on our test carotid arteries: normotension, hypertension (at physiologic flow conditions), and hypertension coupled with elevated flow of canine serum perfusate. In several experiments the effect of endothelial denudation was examined in carotid arteries exposed to normotensive pulsatile flow. A trapped ligand method was used for quantitating low-density lipoprotein uptake and metabolism in the arterial wall. The distribution of both intact and degraded low-density lipoprotein fractions was determined from measurements of radiolabelled low-density lipoprotein activity within thin radial sections of perfused arteries. Our results suggest that both hypertensive hemodynamic simulations exacerbate the uptake of low-density lipoprotein within the arterial wall (by a factor of three to nine). The percentage of low-density lipoprotein that undergoes irreversible degradation falls from 41% under normotensive conditions to below 30% when hypertensive conditions are imposed, indicating that degradative processes are not proportionally elevated with the accelerated influx. A similar pattern is observed for deendothelialized vessels.

  12. Lipid composition of circulating multiple-modified low density lipoprotein.

    PubMed

    Zakiev, E R; Sukhorukov, V N; Melnichenko, A A; Sobenin, I A; Ivanova, E A; Orekhov, A N

    2016-01-01

    Atherogenic modified low- density lipoprotein (LDL) induces pronounced accumulation of cholesterol and lipids in the arterial wall, while native LDL seems to lack such capability. Therefore, modified LDL appears to be a major causative agent in the pathogenesis of atherosclerosis. Possible modifications of LDL particles include changes in size and density, desialylation, oxidation and acquisition of negative charge. Total LDL isolated from pooled plasma of patients with coronary atherosclerosis, as well as from healthy subjects contains two distinct subfractions: normally sialylated LDL and desialylated LDL, which can be isolated by binding to a lectin affinity column. We called the desialylated LDL subfraction circulating modified LDL (cmLDL). In this study, we focused on lipid composition of LDL particles, analysing the total LDL preparation and two LDL subfractions: cmLDL and native LDL. The composition of LDL was studied using thin-layer chromatography. We found that cmLDL subfraction had decreased levels of free and esterified cholesterol, triglycerides, phospholipids (except for lysophosphatidylcholine) and sphingomyelin in comparison to native LDL. On the other hand, levels of mono-, and diglycerides, lysophosphatidylcholine and free fatty acids were higher in cmLDL than in native LDL. Our study demonstrated that lipid composition of cmLDL from atherosclerotic patients was altered in comparison to healthy subjects. In particular, phospholipid content was decreased, and free fatty acids levels were increased in cmLDL. This strengthens the hypothesis of multiple modification of LDL particles in the bloodstream and underscores the clinical importance of desialylated LDL as a possible marker of atherosclerosis progression. PMID:27558696

  13. Thermal stability of human plasma electronegative low-density lipoprotein: A paradoxical behavior of low-density lipoprotein aggregation.

    PubMed

    Rull, Anna; Jayaraman, Shobini; Gantz, Donald L; Rivas-Urbina, Andrea; Pérez-Cuellar, Montserrat; Ordóñez-Llanos, Jordi; Sánchez-Quesada, Jose Luis; Gursky, Olga

    2016-09-01

    Low-density lipoprotein (LDL) aggregation is central in triggering atherogenesis. A minor fraction of electronegative plasma LDL, termed LDL(-), plays a special role in atherogenesis. To better understand this role, we analyzed the kinetics of aggregation, fusion and disintegration of human LDL and its fractions, LDL(+) and LDL(-). Thermal denaturation of LDL was monitored by spectroscopy and electron microscopy. Initially, LDL(-) aggregated and fused faster than LDL(+), but later the order reversed. Most LDL(+) disintegrated and precipitated upon prolonged heating. In contrast, LDL(-) partially retained lipoprotein morphology and formed soluble aggregates. Biochemical analysis of all fractions showed no significant degradation of major lipids, mild phospholipid oxidation, and an increase in non-esterified fatty acid (NEFA) upon thermal denaturation. The main baseline difference between LDL subfractions was higher content of NEFA in LDL(-). Since NEFA promote lipoprotein fusion, increased NEFA content can explain rapid initial aggregation and fusion of LDL(-) but not its resistance to extensive disintegration. Partial hydrolysis of apoB upon heating was similar in LDL subfractions, suggesting that minor proteins importantly modulate LDL disintegration. Unlike LDL(+), LDL(-) contains small amounts of apoA-I and apoJ. Addition of exogenous apoA-I to LDL(+) hampered lipoprotein aggregation, fusion and precipitation, while depletion of endogenous apoJ had an opposite effect. Therefore, the initial rapid aggregation of LDL(-) is apparently counterbalanced by the stabilizing effects of minor proteins such as apoA-I and apoJ. These results help identify key determinants for LDL aggregation, fusion and coalescence into lipid droplets in vivo. PMID:27233433

  14. Alloy Design Challenge: Development of Low Density Superalloys for Turbine Blade Applications

    NASA Technical Reports Server (NTRS)

    MacKay, Rebecca A.; Gabb, Timothy P.; Smialek, James L.; Nathal, Michael V.

    2009-01-01

    New low density single crystal (LDS) alloys have been developed for turbine blade applications, which have the potential for significant improvements in the thrust to weight ratio over current production alloys. An innovative alloying strategy was identified to achieve high temperature creep resistance, alloy density reductions, microstructural stability, and cyclic oxidation resistance. The approach relies on the use of molybdenum (Mo) as a potent solid solution strengthener for the nickel (Ni)-base superalloy; Mo has a density much closer to Ni than other refractory elements, such as rhenium (Re) or tungsten (W). A host of testing and microstructural examinations was conducted on the superalloy single crystals, including creep rupture testing, microstructural stability, cyclic oxidation, and hot corrosion. The paper will provide an overview of the single crystal properties that were generated in this new superalloy design space. The paper will also demonstrate the feasibility of this innovative approach of low density single crystal superalloy design. It will be shown that the best LDS alloy possesses the best attributes of three generations of single crystal alloys: the low density of first-generation single crystal alloys, the excellent oxidation resistance of second-generation single crystal alloys, and a creep strength which exceeds that of second and third generation alloys.

  15. Metabolic abnormalities: triglyceride and low-density lipoprotein.

    PubMed

    Krauss, Ronald M; Siri, Patty W

    2004-06-01

    Increased plasma triglyceride and reduced high-density lipoprotein cholesterol are key features of the metabolic syndrome. Although elevated low-density lipoprotein cholesterol is not an integral characteristic of this syndrome, there is commonly an increase in the proportion of small, dense low-density lipoprotein particles. Together, these abnormalities constitute the atherogenic dyslipidemia of the metabolic syndrome. This article reviews the pathophysiology of altered triglyceride and low-density lipoprotein metabolism in the metabolic syndrome, outlines the relationship of these lipoprotein abnormalities to increased risk of coronary heart disease,and highlights the application of this information to clinical practice. The role of reduced high-density lipoprotein in the metabolic syndrome is discussed elsewhere in this issue.

  16. Aircraft Configured for Flight in an Atmosphere Having Low Density

    NASA Technical Reports Server (NTRS)

    Croom, Mark A. (Inventor); Smith, Stephen C. (Inventor); Gelhausen, Paul A. (Inventor); Guynn, Mark D. (Inventor); Hunter, Craig A. (Inventor); Paddock, David A. (Inventor); Riddick, Steven E. (Inventor); Teter, Jr., John E. (Inventor)

    2012-01-01

    An aircraft is configured for flight in an atmosphere having a low density. The aircraft includes a fuselage, a pair of wings, and a rear stabilizer. The pair of wings extends from the fuselage in opposition to one another. The rear stabilizer extends from the fuselage in spaced relationship to the pair of wings. The fuselage, the wings, and the rear stabilizer each present an upper surface opposing a lower surface. The upper and lower surfaces have X, Y, and Z coordinates that are configured for flight in an atmosphere having low density.

  17. Low density microcellular carbon foams and method of preparation

    DOEpatents

    Arnold, C. Jr.; Aubert, J.H.; Clough, R.L.; Rand, P.B.; Sylwester, A.P.

    1988-06-20

    A low density, open-celled microcellular carbon foam is disclosed which is prepared by dissolving a carbonizable polymer or copolymer in a solvent, pouring the solution into a mold, cooling the solution, removing the solvent, and then carbonizing the polymer or copolymer in a high temperature oven to produce the foam. If desired, an additive can be introduced in order to produce a doped carbon foam, and the foams can be made isotropic by selection of a suitable solvent. The low density, microcellular foams produced by this process are particularly useful in the fabrication of inertial confinement fusion targets, but can also be used as catalysts, absorbents, and electrodes.

  18. Numerical Simulation of Low-Density Shock-Wave Interactions

    NASA Technical Reports Server (NTRS)

    Glass, Christopher E.

    1999-01-01

    Computational Fluid Dynamics (CFD) numerical simulations of low-density shock-wave interactions for an incident shock impinging on a cylinder have been performed. Flow-field density gradient and surface pressure and heating define the type of interference pattern and corresponding perturbations. The maximum pressure and heat transfer level and location for various interaction types (i.e., shock-wave incidence with respect to the cylinder) are presented. A time-accurate solution of the Type IV interference is employed to demonstrate the establishment and the steadiness of the low-density flow interaction.

  19. Low density microcellular carbon foams and method of preparation

    DOEpatents

    Arnold, Jr., Charles; Aubert, James H.; Clough, Roger L.; Rand, Peter B.; Sylwester, Alan P.

    1989-01-01

    A low density, open-celled microcellular carbon foam is disclosed which is prepared by dissolving a carbonizable polymer or copolymer in a solvent, pouring the solution into a mold, cooling the solution, removing the solvent, and then carbonizing the polymer or copolymer in a high temperature oven to produce the foam. If desired, an additive can be introduced in order to produce a doped carbon foam, and the foams can be made isotropic by selection of a suitable solvent. The low density, microcellular foams produced by this process are particularly useful in the fabrication of inertial confinement fusion targets, but can also be used as catalysts, absorbents, and electrodes.

  20. Dynamics and Diffusion Mechanism of Low-Density Liquid Silicon.

    PubMed

    Shen, B; Wang, Z Y; Dong, F; Guo, Y R; Zhang, R J; Zheng, Y X; Wang, S Y; Wang, C Z; Ho, K M; Chen, L Y

    2015-11-25

    A first-order phase transition from a high-density liquid to a low-density liquid has been proposed to explain the various thermodynamic anomies of water. It also has been proposed that such liquid-liquid phase transition would exist in supercooled silicon. Computer simulation studies show that, across the transition, the diffusivity drops roughly 2 orders of magnitude, and the structures exhibit considerable tetrahedral ordering. The resulting phase is a highly viscous, low-density liquid silicon. Investigations on the atomic diffusion of such a novel form of liquid silicon are of high interest. Here we report such diffusion results from molecular dynamics simulations using the classical Stillinger-Weber (SW) potential of silicon. We show that the atomic diffusion of the low-density liquid is highly correlated with local tetrahedral geometries. We also show that atoms diffuse through hopping processes within short ranges, which gradually accumulate to an overall random motion for long ranges as in normal liquids. There is a close relationship between dynamical heterogeneity and hopping process. We point out that the above diffusion mechanism is closely related to the strong directional bonding nature of the distorted tetrahedral network. Our work offers new insights into the complex behavior of the highly viscous low density liquid silicon, suggesting similar diffusion behaviors in other tetrahedral coordinated liquids that exhibit liquid-liquid phase transition such as carbon and germanium.

  1. Low-density microarray technologies for rapid human norovirus genotyping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human noroviruses cause up to 21 million cases of foodborne disease in the United States annually and are the most common cause of acute gastroenteritis in industrialized countries. To reduce the burden of foodborne disease associated with viruses, the use of low density DNA microarrays in conjuncti...

  2. Dynamics and diffusion mechanism of low-density liquid silicon

    DOE PAGESBeta

    Shen, B.; Wang, Z. Y.; Dong, F.; Guo, Y. R.; Zhang, R. J.; Zheng, Y. X.; Wang, S. Y.; Wang, C. Z.; Ho, K. M.; Chen, L. Y.

    2015-11-05

    A first-order phase transition from a high-density liquid to a low-density liquid has been proposed to explain the various thermodynamic anomies of water. It also has been proposed that such liquid–liquid phase transition would exist in supercooled silicon. Computer simulation studies show that, across the transition, the diffusivity drops roughly 2 orders of magnitude, and the structures exhibit considerable tetrahedral ordering. The resulting phase is a highly viscous, low-density liquid silicon. Investigations on the atomic diffusion of such a novel form of liquid silicon are of high interest. Here we report such diffusion results from molecular dynamics simulations using themore » classical Stillinger–Weber (SW) potential of silicon. We show that the atomic diffusion of the low-density liquid is highly correlated with local tetrahedral geometries. We also show that atoms diffuse through hopping processes within short ranges, which gradually accumulate to an overall random motion for long ranges as in normal liquids. There is a close relationship between dynamical heterogeneity and hopping process. We point out that the above diffusion mechanism is closely related to the strong directional bonding nature of the distorted tetrahedral network. Here, our work offers new insights into the complex behavior of the highly viscous low density liquid silicon, suggesting similar diffusion behaviors in other tetrahedral coordinated liquids that exhibit liquid–liquid phase transition such as carbon and germanium.« less

  3. Dynamics and diffusion mechanism of low-density liquid silicon

    SciTech Connect

    Shen, B.; Wang, Z. Y.; Dong, F.; Guo, Y. R.; Zhang, R. J.; Zheng, Y. X.; Wang, S. Y.; Wang, C. Z.; Ho, K. M.; Chen, L. Y.

    2015-11-05

    A first-order phase transition from a high-density liquid to a low-density liquid has been proposed to explain the various thermodynamic anomies of water. It also has been proposed that such liquid–liquid phase transition would exist in supercooled silicon. Computer simulation studies show that, across the transition, the diffusivity drops roughly 2 orders of magnitude, and the structures exhibit considerable tetrahedral ordering. The resulting phase is a highly viscous, low-density liquid silicon. Investigations on the atomic diffusion of such a novel form of liquid silicon are of high interest. Here we report such diffusion results from molecular dynamics simulations using the classical Stillinger–Weber (SW) potential of silicon. We show that the atomic diffusion of the low-density liquid is highly correlated with local tetrahedral geometries. We also show that atoms diffuse through hopping processes within short ranges, which gradually accumulate to an overall random motion for long ranges as in normal liquids. There is a close relationship between dynamical heterogeneity and hopping process. We point out that the above diffusion mechanism is closely related to the strong directional bonding nature of the distorted tetrahedral network. Here, our work offers new insights into the complex behavior of the highly viscous low density liquid silicon, suggesting similar diffusion behaviors in other tetrahedral coordinated liquids that exhibit liquid–liquid phase transition such as carbon and germanium.

  4. Effective thermal conductivity determination for low-density insulating materials

    NASA Technical Reports Server (NTRS)

    Williams, S. D.; Curry, D. M.

    1978-01-01

    That nonlinear least squares can be used to determine effective thermal conductivity was demonstrated, and a method for assessing the relative error associated with these predicted values was provided. The differences between dynamic and static determination of effective thermal conductivity of low-density materials that transfer heat by a combination of conduction, convection, and radiation were discussed.

  5. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein...

  6. The antigenic similarity of human low density lipoproteins.

    PubMed

    LEVINE, L; KAUFFMAN, D L; BROWN, R K

    1955-08-01

    THE FOLLOWING HUMAN LOW DENSITY LIPOPROTEINS WERE PREPARED: beta-lipoproteins of densities greater than 1.040 (A, B,C) a beta-lipoprotein of -S(1.063) = 5 (D), a lipoprotein of -S(1.063) = 19 (E), and a lipoprotein of -S(1.063) = 70 (F). Data are presented which show the immunochemical homogeneity of the D lipoprotein rabbit-anti-D lipoprotein system. Cross-reactions between antibody to A and D lipoproteins and the above lipoproteins have been demonstrated by quantitative precipitation, quanitative complement fixation, and single and double diffusion in agar. The antigenic similarities appear to be associated with the protein portions of the molecule. The antisera produced did not differentiate the low density lipoprotein classes. PMID:13242737

  7. Method of making a cellulose acetate low density microcellular foam

    DOEpatents

    Rinde, James A.

    1978-01-01

    Low-density microcellular foam having a cell size of not greater than 2 .mu.m and method of making by dissolving cellulose acetate in an acetone-based solvent, gelling the solution in a water bath maintained at 0-10.degree. C for a selected period of time to allow impurities to diffuse out, freezing the gel, and then freeze-drying wherein water and solvents sublime and the gel structure solidifies into low-density microcellular foam. The foam has a density of 0.065 to 0.6.times.10.sup.3 kg/m.sup.3 and cell size of about 0.3 to 2 .mu.m. The small cell size foam is particularly adaptable for encapsulation of laser targets.

  8. Low-density microcellular foam and method of making same

    DOEpatents

    Rinde, James A.

    1977-01-01

    Low-density microcellular foam having a cell size of not greater than 2 .mu.m and method of making by dissolving cellulose acetate in an acetone-based solvent, gelling the solution in a water bath maintained at 0.degree.-10.degree. C for a selected period of time to allow impurities to diffuse out, freezing the gel, and then freeze-drying wherein water and solvents sublime and the gel structure solidifies into low-density microcellular foam. The foam has a density of 0.065 to 0.6.times.10.sup.3 kg/m.sup.3 and cell size of about 0.3 to 2 .mu.m. The small cell size foam is particularly applicable for encapsulation of laser targets.

  9. Hydromagnetic wave heating of the low-density interstellar medium

    NASA Technical Reports Server (NTRS)

    Ferriere, Katia M.; Zweibel, Ellen G.; Shull, J. Michael

    1988-01-01

    A simple model for supernova remnant sources of MHD waves is used to calculate the energy spectrum of waves in the intercloud medium and the heating rate resulting from their dissipation. Models of thermal phases of interstellar gas in ionization and thermal equilibrium are then constructed, and it is demonstrated that wave dissipation can be an important heating mechanism which can account for the observed high H I temperatures in low-density (intercloud) neutral gas.

  10. Are most low-density knapsacks solvable in polynomial time

    SciTech Connect

    Brickell, E.F.

    1983-01-01

    In this paper, we show how techniques similar to those developed for breaking the cryptosystems can be used to solve knapsacks of low density. In the examples we have run, the algorithm has always been successful on knapsacks of density less than or equal to 1/2. We show, based on one assumption, that the algorithm will succeed on most knapsacks of density less than or equal to 1/3.

  11. Silylation of low-density silica and bridged polysilsesquioxane aerogels

    SciTech Connect

    DeFriend, K. A.; Loy, D. A.; Salazar, K. V.; Wilson, K. V.

    2004-01-01

    Silica and bridged polysilsesquioxane aerogels are low-density materials that are attractive for applications such as thermal insulation, porous separation media or catalyst supports, adsorbents, and cometary dust capture agents. However, aerogels are notoriously weak and brittle making it difficult to handle and machine monoliths into desired forms. This complication prevents the development of many applications that would otherwise benefit from the use of the low-density materials. Here, we will describe our efforts to chemically modify and mechanically enhance silica-based aerogels using chemical vapor techniques without sacrificing their characteristic low densities. Monolithic silica and organic-bridged polysilsesquioxane aerogels were prepared by sol-gel polymerization of the respective methoxysilane monomers followed by supercritical carbon dioxide drying of the gels. Then the gels were reactively modified with silylating agents to demonstrate the viability of CVD modification of aerogels, and to determine the effects of silylation of surface silanols on the morphology, surface area, and mechanical properties of the resulting aerogels.

  12. Microcraters formed in glass by low density projectiles

    NASA Technical Reports Server (NTRS)

    Mandeville, J.-C.; Vedder, J. F.

    1971-01-01

    Microcraters were produced in soda-lime glass by the impact of low density projectiles of polystyrene with masses between 0.7 and 62 picograms and velocities between 2 and 14 kilometers per second. The morphology of the craters depends on the velocity and angle of incidence of the projectiles. The transitions in morphology of the craters formed by polystyrene spheres occur at higher velocities than they do for more dense projectiles. For oblique impact, the craters are elongated and shallow with the spallation threshold occuring at higher velocity. For normal incidence, the total displaced mass of the target material per unit of projectile kinetic energy increases slowly with the energy.

  13. Performance of Low-Density Parity-Check Coded Modulation

    NASA Technical Reports Server (NTRS)

    Hamkins, Jon

    2010-01-01

    This paper reports the simulated performance of each of the nine accumulate-repeat-4-jagged-accumulate (AR4JA) low-density parity-check (LDPC) codes [3] when used in conjunction with binary phase-shift-keying (BPSK), quadrature PSK (QPSK), 8-PSK, 16-ary amplitude PSK (16- APSK), and 32-APSK.We also report the performance under various mappings of bits to modulation symbols, 16-APSK and 32-APSK ring scalings, log-likelihood ratio (LLR) approximations, and decoder variations. One of the simple and well-performing LLR approximations can be expressed in a general equation that applies to all of the modulation types.

  14. Preparation, testing, and delivery of low density polyimide foam panels

    NASA Technical Reports Server (NTRS)

    Ball, G. L., III; Post, L. K.; Salyer, I. O.

    1975-01-01

    Plastic foams based on polyimide resins were shown to be stable at relatively high temperatures, and to possess very low flame spread and smoke generation characteristics. A system and process were developed to prepare low-density polyimide foam from a liquid formulation. The system is based on the reaction of micropulverized grade pyromellitic dianhydride with a polymeric diisocyanate. The panels produced were postcured at elevated temperatures to achieve maximum thermal and fire resistance, and incorporation of a fire retardant into the formulation was considered. The effects of a flame retardant (Flameout 5600B1) were investigated, but eliminated in preference to the postcuring approach.

  15. Advanced Porous Coating for Low-Density Ceramic Insulation Materials

    NASA Technical Reports Server (NTRS)

    Leiser, Daniel B.; Churchward, Rex; Katvala, Victor; Stewart, David; Balter, Aliza

    1988-01-01

    The need for improved coatings on low-density reusable surface insulation (RSI) materials used on the space shuttle has stimulated research into developing tougher coatings. The processing of a new porous composite "coating" for RST called toughened unipiece fibrous insulation Is discussed. Characteristics including performance in a simulated high-speed atmospheric entry, morphological structure before and after this exposure, resistance to Impact, and thermal response to a typical heat pulse are described. It is shown that this coating has improved impact resistance while maintaining optical and thermal properties comparable to the previously available reaction-cured glass coating.

  16. Venting and High Vacuum Performance of Low Density Multilayer Insulation

    NASA Astrophysics Data System (ADS)

    Riesco, M. E.; McLean, C. H.; Mills, G. L.; Buerger, S.; Meyer, M. L.

    2010-04-01

    The NASA Exploration Program is currently studying the use liquid oxygen, liquid methane and liquid hydrogen for propulsion in future spacecraft for Exploration of the Moon and Mars. This will require the efficient long term, on-orbit storage of these cryogenic propellants. Multilayer Insulation (MLI) will be critical to achieving the required thermal performance since it has much lower heat transfer than any other insulation when used in a vacuum. MLI with a low density (⩽10 layers/cm) has been shown in previous work to be the most mass efficient. The size and mass constraints of these propulsion systems will not allow a structural shell to be used to provide vacuum for the MLI during ground hold and launch. The baseline approach is to purge the MLI during ground hold with an inert gas which is then vented during launch ascent and on-orbit. This paper presents the results on experimental tests and modeling performed by Ball Aerospace on low density, non-perforated MLI used to insulate a cryogenic tank simulating an Exploration cryogenic propellant storage vessel. These include measurements of the rate of venting and of the heat transfer of gas filled insulation, fully evacuated insulation and during the transition in between. Results of transient computer modeling of the MLI venting and heat transfer process are also presented. Previous work by some of the authors performed vent testing using MLI with perforations and slits and a slow pump down rate.

  17. Highwall damage control using presplitting with low-density explosives

    SciTech Connect

    Stachura, V.J.; Cumerlato, C.L.

    1995-12-31

    The US Bureau of Mines is conducting research on blasting methods that reduce highwall overbreak and the associated rockfall hazards. This paper presents the results of tests using a low-density water gel to improve the quality of air-decked presplit blasts at a surface coal mine in New Mexico. The explosive`s specific gravity averaged 0.50 and was bulk loaded using a modified truck which injected the gassing agent. Reductions in overbreak and resulting rockfall were achieved in comparison to a highwall presplit with ANFO. The test sections used 15{degree} angled blast holes and resulted in 1,119 m of air deck presplit highwall using a low-density water gel which was then compared to 894 m of highwall shot with an ANFO air decked presplit design. The total quantity of explosives per hole ranged from 68 to 113 kg and the 27 cm holes were 19- to 33-m deep on 5.5 m centers. Periodic visual examination and photographic surveys of the highwall test areas were used to document the amount of rockfall. In addition, laser profiles of selected sections were conducted to further delineate the damage and highwall contour differences.

  18. A Langevin model for low density pedestrian dynamics

    NASA Astrophysics Data System (ADS)

    Corbetta, Alessandro; Lee, Chung-Min; Benzi, Roberto; Muntean, Adrian; Toschi, Federico

    The dynamics of pedestrian crowds shares deep connections with statistical physics and fluid dynamics. Reaching a quantitative understanding, not only of the average behaviours but also of the statistics of (rare) fluctuations would have major impact, for instance, on the design and safety of civil infrastructures. A key feature of pedestrian dynamics is its strong intrinsic variability, that we can already observe at the single individual level. In this work we aim at a quantitative characterisation of this statistical variability by studying individual fluctuations. We consider experimental observations of low-density pedestrian flows in a corridor within a building at Eindhoven University of Technology. Few hundreds of thousands of pedestrian trajectories with high space and time resolutions have been collected via a Microsoft Kinect 3D-range sensor and automatic head tracking techniques. From these observations we model pedestrians as active Brownian particles by means of a generalised Langevin equation. With this model we can quantitatively reproduce the observed dynamics including the statistics of ordinary pedestrian fluctuations and of rarer U-turn events. Low density, pair-wise interactions between pedestrians are also discussed.

  19. Relationship between Exploding Bridgewire & Spark Initiation of Low Density PETN

    NASA Astrophysics Data System (ADS)

    Lee, Elizabeth; Drake, Rod

    2015-06-01

    Recent work has shown that the energy delivered after bridgewire burst affects the function time of an EBW detonator. The spark which is formed post bridgewire burst is the means by which the remaining fireset energy is delivered into the detonator. Therefore, by studying the characteristics of spark-gap detonators insight into the contribution of spark initiation to the functioning of EBW detonators may be achieved. Spark initiation of low density explosives consists of; (i) spark formation, (ii) spark interaction with the bed, and (iii) ignition and growth of reaction. Experiments were performed in which beds of an inert simulant were used to study the formation and propagation of sparks. The effect of the spark on inert porous beds was studied over a limited delivered energy range. The disruption of the bed was found to be dependent on the particle size / pore structure of the bed. The effect of spark initiation on a low density PETN bed was then examined, the relationship between delivered energy and function time was found to be the same as for EBW detonators. This necessitated the development of electrical diagnostic techniques to measure the energy delivered to the spark.

  20. Low-Density, Aerogel-Filled Thermal-Insulation Tiles

    NASA Technical Reports Server (NTRS)

    Santos, Maryann; Heng, Vann; Barney, Andrea; Oka, Kris; Droege, Michael

    2005-01-01

    Aerogel fillings have been investigated in a continuing effort to develop low-density thermal-insulation tiles that, relative to prior such tiles, have greater dimensional stability (especially less shrinkage), equal or lower thermal conductivity, and greater strength and durability. In preparation for laboratory tests of dimensional and thermal stability, prototypes of aerogel-filled versions of recently developed low-density tiles have been fabricated by impregnating such tiles to various depths with aerogel formations ranging in density from 1.5 to 5.6 lb/ft3 (about 53 to 200 kg/cu m). Results available at the time of reporting the information for this article showed that the thermal-insulation properties of the partially or fully aerogel- impregnated tiles were equivalent or superior to those of the corresponding non-impregnated tiles and that the partially impregnated tiles exhibited minimal (<1.5 percent) shrinkage after multiple exposures at a temperature of 2,300 F (1,260 C). Latest developments have shown that tiles containing aerogels at the higher end of the density range are stable after multiple exposures at the said temperature.

  1. Radiotracers for low density lipoprotein biodistribution studies in vivo: technetium-99m low density lipoprotein versus radioiodinated low density lipoprotein preparations

    SciTech Connect

    Vallabhajosula, S.; Paidi, M.; Badimon, J.J.; Le, N.A.; Goldsmith, S.J.; Fuster, V.; Ginsberg, H.N.

    1988-07-01

    In an attempt to characterize the in vivo behavior of (99mTc) low density lipoprotein (LDL), biodistribution studies were performed in normal and hypercholesterolemic (HC) rabbits. In normal rabbits, 24 hr after the injection of (99mTc)LDL, 99mTc activity accumulated mainly in adrenal glands, spleen, liver, and kidney. In HC rabbits, however, there was a marked reduction of 99mTc activity in these organs. In both normal and HC rabbits, less than 17% of 99mTc activity appeared in the 24-hr urine following injection of (99mTc)LDL, suggesting that in vivo, (99mTc)LDL is trapped and accumulated within the tissues. Direct comparison of (99mTc)LDL, 125I-native-LDL and (131I)tyramine cellobiose-LDL (the previously validated trapped radioligand) in normal rabbits, demonstrated that the biodistribution of (99mTc)LDL was similar to that of (131I)tyramine cellobiose-LDL. The adrenal glands, liver, and spleen accumulated significantly greater quantities of 99mTc and 131I activity per gram of tissue than 125I (from native-LDL). In addition, imaging studies in monkeys, showed that the hepatic uptake and retention of (99mTc) LDL was similar to that of (131I)tyramine cellobiose LDL. In contrast, radioiodine from native-LDL was deiodinated in liver with subsequent excretion into the intestine. These results suggest that (99mTc)LDL acts as a trapped ligand in vivo and should therefore, be a good tracer for noninvasive quantitative biodistribution studies of LDL.

  2. Radiotracers for low density lipoprotein biodistribution studies in vivo: technetium-99m low density lipoprotein versus radioiodinated low density lipoprotein preparations.

    PubMed

    Vallabhajosula, S; Paidi, M; Badimon, J J; Le, N A; Goldsmith, S J; Fuster, V; Ginsberg, H N

    1988-07-01

    In an attempt to characterize the in vivo behavior of [99mTc] low density lipoprotein (LDL), biodistribution studies were performed in normal and hypercholesterolemic (HC) rabbits. In normal rabbits, 24 hr after the injection of [99mTc]LDL, 99mTc activity accumulated mainly in adrenal glands, spleen, liver, and kidney. In HC rabbits, however, there was a marked reduction of 99mTc activity in these organs. In both normal and HC rabbits, less than 17% of 99mTc activity appeared in the 24-hr urine following injection of [99mTc]LDL, suggesting that in vivo, [99mTc]LDL is trapped and accumulated within the tissues. Direct comparison of [99mTc]LDL, 125I-native-LDL and [131I]tyramine cellobiose-LDL (the previously validated trapped radioligand) in normal rabbits, demonstrated that the biodistribution of [99mTc]LDL was similar to that of [131I]tyramine cellobiose-LDL. The adrenal glands, liver, and spleen accumulated significantly greater quantities of 99mTc and 131I activity per gram of tissue than 125I (from native-LDL). In addition, imaging studies in monkeys, showed that the hepatic uptake and retention of [99mTc] LDL was similar to that of [131I]tyramine cellobiose LDL. In contrast, radioiodine from native-LDL was deiodinated in liver with subsequent excretion into the intestine. These results suggest that [99mTc]LDL acts as a trapped ligand in vivo and should therefore, be a good tracer for noninvasive quantitative biodistribution studies of LDL.

  3. Self-assembled SnO2 film with low density

    NASA Astrophysics Data System (ADS)

    Ji, Hongjun; Liu, Xiaoheng; Wang, Xin; Yang, Xujie; Lu, Lude; Ge, Xiutao; Li, Yonghong

    2009-03-01

    A new kind of metallic oxide film consisted of nanodisks with porous structure has been prepared, which is different from that of targetlike multirings previously reported by our group. Herein, the SnO2 film has been prepared by using tin(IV) tert-butoxide as precursor, sodium dodecyl sulfonate (SDS) as template and gelatin as stabilizer. Results show that the SnO2 film is usually composed of series nanodisks with the diameters ranging from 0.1μm to 1μm and each disk displays worm-like porous structure in the transmission electron microscope (TEM) observation. These SnO2 nanodisks are suggested to born inside the solution and gradually rise up to the air-water interface due to low density of the disk or disk cluster. After further treatment, the well ordered SnO2 thin film is considered to have a potential application in gas-sensing materials. Remarkably, this may be a distinctive method to get SnO2 film and may be widely applied to produce other metallic oxide films with low density.

  4. Effect of nanoclay on the properties of low density polyethylene/linear low density polyethylene/thermoplastic starch blend films.

    PubMed

    Sabetzadeh, Maryam; Bagheri, Rouhollah; Masoomi, Mahmood

    2016-05-01

    The aim of this work is to study effect of nanoclay (Cloisite(®)15A) on morphology and properties of low-density polyethylene/linear low-density polyethylene/thermoplastic starch (LDPE/LLDPE/TPS) blend films. LDPE/LLDPE blend (70/30wt/wt) containing 15wt.% TPS in the presence of PE-grafted maleic anhydride (PE-g-MA, 3wt.%) with 1, 3 and 5phr of nanoclay are compounded in a twin-screw extruder and then film blown using a blowing machine. Nanocomposites with intercalated structures are obtained, based on the X-ray diffraction (XRD) and transmission electron microscopy (TEM) studies. However, some exfoliated single platelets in the samples are also observable. Scanning electron microscopic (SEM) images confirm the ability of both exfoliated nanoclay and PE-g-MA to reduce the size of TPS domains and deform their particles within the PE matrices. As the nanoclay content increases from 1 to 5phr, the tensile strength, tear resistance and impact strength of the films increase, whereas a slight decrease in the elongation at break is observed. The film samples with 5phr nanoclay possess the required packaging properties, as specified by ASTM D4635. These films provide desired optical transparency and surface roughness which are more attractive for packaging applications. PMID:26876998

  5. Dot-blot assay for the low density lipoprotein receptor

    SciTech Connect

    Maggi, F.M.; Catapano, A.L.

    1987-01-01

    We describe a new method for detecting the interaction of low density lipoprotein with its receptor using unmodified nitrocellulose as support for membrane protein. The method is specific and sensitive down to 3 micrograms of membrane protein. Unlabeled LDL, but not HDL, competes with /sup 125/I-labeled LDL for binding, and binding is abolished by pretreatment of the membranes with pronase and is dependent upon the presence of Ca2+. Furthermore, modification of arginine or lysine residues on LDL abolishes the lipoprotein interaction with the receptor protein supported on the nitrocellulose. When the membranes are solubilized with octyl glucoside, purification steps of the receptor can be directly followed with no interference of the detergent, therefore eliminating the need for its removal. The increased expression of LDL receptors on liver membranes from estradiol-treated rats was also demonstrated. We suggest, therefore, that this method can be used to detect the presence of LDL receptors on minute amounts of membrane protein.

  6. Monitoring low density avian populations: An example using Mountain Plovers

    USGS Publications Warehouse

    Dreitz, V.J.; Lukacs, P.M.; Knopf, F.L.

    2006-01-01

    Declines in avian populations highlight a need for rigorous, broad-scale monitoring programs to document trends in avian populations that occur in low densities across expansive landscapes. Accounting for the spatial variation and variation in detection probability inherent to monitoring programs is thought to be effort-intensive and time-consuming. We determined the feasibility of the analytical method developed by Royle and Nichols (2003), which uses presence-absence (detection-non-detection) field data, to estimate abundance of Mountain Plovers (Charadrius montanus) per sampling unit in agricultural fields, grassland, and prairie dog habitat in eastern Colorado. Field methods were easy to implement and results suggest that the analytical method provides valuable insight into population patterning among habitats. Mountain Plover abundance was highest in prairie dog habitat, slightly lower in agricultural fields, and substantially lower in grassland. These results provided valuable insight to focus future research into Mountain Plover ecology and conservation. ?? The Cooper Ornithological Society 2006.

  7. Ultra-low density microcellular polymer foam and method

    DOEpatents

    Simandl, Ronald F.; Brown, John D.

    1996-01-01

    An ultra-low density, microcellular open-celled polymer foam and a method for making such foam. A polymer is dissolved in a heated solution consisting essentially of at least one solvent for the dissolution of the polymer in the heated solution and the phase inversion of the dissolved polymer to a liquid gel upon sufficient cooling of the heated solution. The heated solution is contained in a containment means provided with a nucleating promoting means having a relatively rough surface formed of fixed nucleating sites. The heated solution is cooled for a period of time sufficient to form a liquid gel of the polymer by phase inversion. From the gel, a porous foam having a density of less than about 12.0 mg/cm.sup.3 and open porosity provided by well interconnected strut morphology is formed.

  8. Ultra-low density microcellular polymer foam and method

    DOEpatents

    Simandl, R.F.; Brown, J.D.

    1996-03-19

    An ultra-low density, microcellular open-celled polymer foam and a method for making such foam are disclosed. A polymer is dissolved in a heated solution consisting essentially of at least one solvent for the dissolution of the polymer in the heated solution and the phase inversion of the dissolved polymer to a liquid gel upon sufficient cooling of the heated solution. The heated solution is contained in a containment means provided with a nucleating promoting means having a relatively rough surface formed of fixed nucleating sites. The heated solution is cooled for a period of time sufficient to form a liquid gel of the polymer by phase inversion. From the gel, a porous foam having a density of less than about 12.0 mg/cm{sup 3} and open porosity provided by well interconnected strut morphology is formed.

  9. Ultra-low density microcellular polymer foam and method

    SciTech Connect

    Simandl, R.F.; Brown, J.D.

    1995-12-31

    An ultra-low density, microcellular open-celled polymer foam and a method for making such foam are disclosed. A polymer is dissolved in a heated solution consisting essentially of at least one solvent for the dissolution of the polymer in the heated solution and the phase inversion of the dissolved polymer to a liquid gel upon sufficient cooling of the heated solution. The heated solution is contained in a containment means provided with a nucleating promoting means having a relatively rough surface formed of fixed nucleating sites. The heated solution is cooled for a period of time sufficient to form a liquid gel of the polymer by phase inversion. From the gel, a porous foam having a density of less than about 12.0 mg/cm{sup 3} and open porosity provided by well interconnected strut morphology is formed. These foams can be used for ICF targets.

  10. Low Density Parity Check Codes: Bandwidth Efficient Channel Coding

    NASA Technical Reports Server (NTRS)

    Fong, Wai; Lin, Shu; Maki, Gary; Yeh, Pen-Shu

    2003-01-01

    Low Density Parity Check (LDPC) Codes provide near-Shannon Capacity performance for NASA Missions. These codes have high coding rates R=0.82 and 0.875 with moderate code lengths, n=4096 and 8176. Their decoders have inherently parallel structures which allows for high-speed implementation. Two codes based on Euclidean Geometry (EG) were selected for flight ASIC implementation. These codes are cyclic and quasi-cyclic in nature and therefore have a simple encoder structure. This results in power and size benefits. These codes also have a large minimum distance as much as d,,, = 65 giving them powerful error correcting capabilities and error floors less than lo- BER. This paper will present development of the LDPC flight encoder and decoder, its applications and status.

  11. The tethered satellite system for low density aerothermodynamics studies

    NASA Technical Reports Server (NTRS)

    Carlomagno, Giovanni M.; De Luca, Luigi; Siemers, P. M., III; Wood, George M., Jr.

    1986-01-01

    The feasibility of the operation of the Tethered Satellite System (TSS) as a continuous open wind tunnel for low-density aerothermodynamic studies (applicable to the design of hypersonic space vehicles including STARFAC, AOTV, and ERV) is considered. The Shuttle Continuous Open Wind Tunnel (SCOWT) program, for the study of the energy and momentum transfer between the tethered satellite and its environmental medium during the TSS/2 mission, is described. Instrumentation and TSS design requirements to meet SCOWT objectives are also considered. SCOWT will provide information on the gasdynamic processes occurring downstream of the bow wave standing in front of the TS, the chemistry and physics of the upper atmosphere related to satellite aerothermodynamics, and TSS's overall experimental envelope of operation.

  12. Low-density silicon allotropes for photovoltaic applications

    NASA Astrophysics Data System (ADS)

    Amsler, Maximilian; Botti, Silvana; Marques, Miguel A. L.; Lenosky, Thomas J.; Goedecker, Stefan

    2015-07-01

    Silicon materials play a key role in many technologically relevant fields, ranging from the electronic to the photovoltaic industry. A systematic search for silicon allotropes was performed by employing a modified ab initio minima hopping crystal structure prediction method. The algorithm was optimized to specifically investigate the hitherto barely explored low-density regime of the silicon phase diagram by imitating the guest-host concept of clathrate compounds. In total, 44 metastable phases are presented, of which 11 exhibit direct or quasidirect band gaps in the range of ≈1.0-1.8 eV, close to the optimal Shockley-Queisser limit of ≈1.4 eV, with a stronger overlap of the absorption spectra with the solar spectrum compared to conventional diamond silicon. Due to the structural resemblance to known clathrate compounds it is expected that the predicted phases can be synthesized.

  13. Ballistics considerations for small-caliber, low-density projectiles

    SciTech Connect

    Gouge, M.J.; Baylor, L.R.; Combs, S.K.; Fisher, P.W.; Foster, C.A.; Foust, C.R.; Milora, S.L.; Qualls, A.L.

    1993-11-01

    One major application for single- and two-stage light gas guns is for fueling magnetic fusion confinement devices. Powder guns are not a feasible alternative due to possible plasma contamination by residual powder gases and the eventual requirement of steady-state operation at {approximately} 1 Hz, which will dictate a closed gas handling system where propellant gases are recovered, processed and recompressed. Interior ballistic calculations for single-stage light gas guns, both analytical and numerical, are compared to an extensive data base for low density hydrogenic projectiles (pellets). Some innovative range diagnostics are described for determining the size and velocity of these small (several mm) size projectiles. A conceptual design of a closed cycle propellant gas system is presented including tradeoffs between different light propellant gases.

  14. KEPLER-7b: A TRANSITING PLANET WITH UNUSUALLY LOW DENSITY

    SciTech Connect

    Latham, David W.; Buchhave, Lars A.; Furesz, Gabor; Geary, John C.; Borucki, William J.; Koch, David G.; Lissauer, Jack J.; Rowe, Jason F.; Brown, Timothy M.; Basri, Gibor; Batalha, Natalie M.; Caldwell, Douglas A.; Jenkins, Jon M.; Cochran, William D.; Dunham, Edward W.; Gautier, Thomas N.; Howell, Steve B.; Marcy, Geoffrey W.; Monet, David G.

    2010-04-20

    We report on the discovery and confirmation of Kepler-7b, a transiting planet with unusually low density. The mass is less than half that of Jupiter, M {sub P} = 0.43 M {sub J}, but the radius is 50% larger, R {sub P} = 1.48 R {sub J}. The resulting density, {rho}{sub P} = 0.17 g cm{sup -3}, is the second lowest reported so far for an extrasolar planet. The orbital period is fairly long, P = 4.886 days, and the host star is not much hotter than the Sun, T {sub eff} = 6000 K. However, it is more massive and considerably larger than the Sun, M {sub *} = 1.35 M {sub sun} and R {sub *} = 1.84 R {sub sun}, and must be near the end of its life on the main sequence.

  15. STANDING WAVE PROBES FOR DIMENSIONAL METROLOGY OF LOW DENSITY FOAMS

    SciTech Connect

    Seugling, R M; Woody, S C; Bauza, M B

    2010-03-23

    Typically, parts and geometries of interest to LLNL are made from a combination of complex geometries and a wide array of different materials ranging from metals and ceramics to low density foams and plastic foils. These parts are combined to develop physics experiments for studying material properties, equation of state (EOS) and radiation transport. Understanding the dimensional uncertainty of the parts contained within an experiment is critical to the physical understanding of the phenomena being observed and represents the motivation for developing probe metrology capability that can address LLNL's unique problems. Standing wave probes were developed for measuring high aspect ratio, micrometer scaled features with nanometer resolution. Originally conceived of for the use in the automotive industry for characterizing fuel injector bores and similar geometries, this concept was investigated and improved for use on geometries and materials important to LLNL needs within target fabrication. As part of the original project, detailed understanding of the probe dynamics and interactions with the surface of the sample was investigated. In addition, the upgraded system was utilized for measuring fuel injector bores and micro-lenses as a means of demonstrating capability. This report discusses the use of the standing wave probe for measuring features in low density foams, 55 mg/cc SiO{sub 2} and 982 mg/cc (%6 relative density) copper foam respectively. These two foam materials represent a difficult metrology challenge because of their material properties and surface topography. Traditional non-contact metrology systems such as normal incident interferometry and/or confocal microscopy have difficulty obtaining a signal from the relatively absorptive characteristics of these materials. In addition to the foam samples, a solid copper and plastic (Rexolite{trademark}) sample of similar geometry was measured with the standing wave probe as a reference for both conductive and

  16. An empirical probability model of detecting species at low densities.

    PubMed

    Delaney, David G; Leung, Brian

    2010-06-01

    False negatives, not detecting things that are actually present, are an important but understudied problem. False negatives are the result of our inability to perfectly detect species, especially those at low density such as endangered species or newly arriving introduced species. They reduce our ability to interpret presence-absence survey data and make sound management decisions (e.g., rapid response). To reduce the probability of false negatives, we need to compare the efficacy and sensitivity of different sampling approaches and quantify an unbiased estimate of the probability of detection. We conducted field experiments in the intertidal zone of New England and New York to test the sensitivity of two sampling approaches (quadrat vs. total area search, TAS), given different target characteristics (mobile vs. sessile). Using logistic regression we built detection curves for each sampling approach that related the sampling intensity and the density of targets to the probability of detection. The TAS approach reduced the probability of false negatives and detected targets faster than the quadrat approach. Mobility of targets increased the time to detection but did not affect detection success. Finally, we interpreted two years of presence-absence data on the distribution of the Asian shore crab (Hemigrapsus sanguineus) in New England and New York, using our probability model for false negatives. The type of experimental approach in this paper can help to reduce false negatives and increase our ability to detect species at low densities by refining sampling approaches, which can guide conservation strategies and management decisions in various areas of ecology such as conservation biology and invasion ecology.

  17. FORMATION AND STRUCTURE OF LOW-DENSITY EXO-NEPTUNES

    SciTech Connect

    Rogers, Leslie A.; Seager, Sara; Bodenheimer, Peter

    2011-09-01

    Kepler has found hundreds of Neptune-size (2-6 R{sub +}) planet candidates within 0.5 AU of their stars. The nature of the vast majority of these planets is not known because their masses have not been measured. Using theoretical models of planet formation, evolution, and structure, we explore the range of minimum plausible masses for low-density exo-Neptunes. We focus on highly irradiated planets with T{sub eq} {>=} 500 K. We consider two separate formation pathways for low-mass planets with voluminous atmospheres of light gases: core-nucleated accretion and outgassing of hydrogen from dissociated ices. We show that Neptune-size planets at T{sub eq} = 500 K with masses as small as a few times that of Earth can plausibly be formed by core-nucleated accretion coupled with subsequent inward migration. We also derive a limiting low-density mass-radius relation for rocky planets with outgassed hydrogen envelopes but no surface water. Rocky planets with outgassed hydrogen envelopes typically have computed radii well below 3 R{sub +}. For both planets with H/He envelopes from core-nucleated accretion and planets with outgassed hydrogen envelopes, we employ planet interior models to map the range of planet mass-envelope mass-equilibrium temperature parameter space that is consistent with Neptune-size planet radii. Atmospheric mass loss mediates which corners of this parameter space are populated by actual planets and ultimately governs the minimum plausible mass at a specified transit radius. We find that Kepler's 2-6 R{sub +} planet candidates at T{sub eq} = 500-1000 K could potentially have masses {approx}< 4 M{sub +}. Although our quantitative results depend on several assumptions, our qualitative finding that warm Neptune-size planets can have masses substantially smaller than those given by interpolating the masses and radii of planets within our Solar System is robust.

  18. Synthesis of Low-Density, Carbon-Doped, Porous Hexagonal Boron Nitride Solids.

    PubMed

    Gautam, Chandkiram; Tiwary, Chandra Sekhar; Jose, Sujin; Brunetto, Gustavo; Ozden, Sehmus; Vinod, Soumya; Raghavan, Prasanth; Biradar, Santoshkumar; Galvao, Douglas Soares; Ajayan, Pulickel M

    2015-12-22

    Here, we report the scalable synthesis and characterization of low-density, porous, three-dimensional (3D) solids consisting of two-dimensional (2D) hexagonal boron nitride (h-BN) sheets. The structures are synthesized using bottom-up, low-temperature (∼300 °C), solid-state reaction of melamine and boric acid giving rise to porous and mechanically stable interconnected h-BN layers. A layered 3D structure forms due to the formation of h-BN, and significant improvements in the mechanical properties were observed over a range of temperatures, compared to graphene oxide or reduced graphene oxide foams. A theoretical model based on Density Functional Theory (DFT) is proposed for the formation of h-BN architectures. The material shows excellent, recyclable absorption capacity for oils and organic solvents. PMID:26580810

  19. Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies

    PubMed Central

    Vanhamme, Luc; Roumeguère, Thierry; Zouaoui Boudjeltia, Karim

    2013-01-01

    Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNFα and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis. PMID:23983406

  20. Properties of Dwarf Ellipticals in Low-Density Environments

    NASA Astrophysics Data System (ADS)

    Sur, Debnil; Guhathakurta, P.; Toloba, E.

    2013-01-01

    Dwarf elliptical galaxies have been studied only in dense cluster environments, where they are the most common type of object. While this suggests that their location affects their formation and evolution, the role of distance is not fully understood. Thus, to investigate the physical processes that shape these galaxies, we have conducted a study of dwarf elliptical galaxies (dEs) in low-density environments to compare their properties with those in clusters. Catalogs of such objects have not been created; thus, we have developed a novel objective method to find new dEs through comparing photometric properties with those of galaxies in the Virgo Cluster Catalog. This method utilizes optical colors, surface brightness and ellipticity, and it confirms smoothness through visual classification. In this last step, we found a very low contamination rate, which suggests the procedure’s utility in finding dEs. Through the NSA Sloan Atlas, we have analyzed the spectrophotometric properties of the dE candidates as a function of distance to the nearest massive galaxy, which we refer to as their host. We have found that these dEs are younger and more actively forming stars than dEs in denser regions. This is consistent with a transformation scenario in which low luminosity spiral galaxies are affected by the environment and transformed into quiescent galaxies. This low density regime contains objects in an intermediate state between the spiral galaxy and the classical dE in Virgo, where no star formation is ongoing. The correlation of the studied properties with the distance to the host galaxy provides new evidence that the dEs are created by a process called ram-pressure stripping: the interstellar medium of a host galaxy removes the gas of a smaller star-forming galaxy and provokes its quenching. We are currently analysing Keck/DEIMOS spectroscopy of some of the dE candidates from our catalog to explore in more detail their connection to cluster dEs. Possible similarities

  1. Performance of Low-Density Parity-Check Coded Modulation

    NASA Astrophysics Data System (ADS)

    Hamkins, J.

    2011-02-01

    This article presents the simulated performance of a family of nine AR4JA low-density parity-check (LDPC) codes when used with each of five modulations. In each case, the decoder inputs are codebit log-likelihood ratios computed from the received (noisy) modulation symbols using a general formula which applies to arbitrary modulations. Suboptimal soft-decision and hard-decision demodulators are also explored. Bit-interleaving and various mappings of bits to modulation symbols are considered. A number of subtle decoder algorithm details are shown to affect performance, especially in the error floor region. Among these are quantization dynamic range and step size, clipping degree-one variable nodes, "Jones clipping" of variable nodes, approximations of the min* function, and partial hard-limiting messages from check nodes. Using these decoder optimizations, all coded modulations simulated here are free of error floors down to codeword error rates below 10^{-6}. The purpose of generating this performance data is to aid system engineers in determining an appropriate code and modulation to use under specific power and bandwidth constraints, and to provide information needed to design a variable/adaptive coded modulation (VCM/ACM) system using the AR4JA codes. IPNPR Volume 42-185 Tagged File.txt

  2. Heterogeneity of serum low density lipoproteins in normal human subjects

    SciTech Connect

    Shen, M.M.S.; Krauss, R.M.; Lindgren, F.T.; Forte, T.M.

    1981-01-01

    Equilibrium density gradient ultracentrifugation of serum low density lipoprotein (LDL) from twelve healthy human subjects was used to separate six subfractions with mean dinsity ranging from 1.0268 to 1.0597 g/ml. Mean corrected peak flotation rate (S/sup o//sub f/) measured by analytic ultracentrifugation, and mean particle diameter determined by negative staining electron microscopy, both declined significantly with increasing density of the subfractions. Major differences in chemical composition of the subfractions were noted, including a singnificantly lower triglyceride content and higher ratio of cholesteryl ester to triglyceride in the middle fractions compared with those of highest and lowest density. Concentration of fraction 2 correlated positively with HDL (P < 0.01) and negatively with VLDL (P < 0.001); concentration of fraction 4 correlated negatively with HDL (P < 0.05) and positively with VLDL (P < 0.001) and IDL (P < 0.01). LDL may thus include subspecies of differing structure and composition which might also have different metabolic and atherogenic roles.

  3. Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages.

    PubMed

    Atrahimovich, Dana; Khatib, Soliman; Sela, Shifra; Vaya, Jacob; Samson, Abraham O

    2016-01-01

    High levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100) that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25-4 μM). Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels. PMID:27516832

  4. Low-density carbonized resorcinol-formaldehyde foams

    SciTech Connect

    Kong, F.M.; Buckley, S.R.; Giles, C.L. Jr.; Haendler, B.L.; Hair, L.M.; Letts, S.A.; Overturf, G.E. III; Price, C.W.; Cook, R.C.

    1991-07-04

    This report documents research and development on resorcinol- formaldehyde-based foam materials conducted between 1986 and June 1990, when the effort was discontinued. The foams discussed are resorcinol-formaldehyde (RF) foam, carbonized RF (CRF) foam, and two composite foams, a polystyrene/RF (PS/RF) foam and its carbonized derivative (CPR). The RF foams are synthesized by the polycondensation of resorcinol with formaldehyde in a slightly basic solution. Their structure and density depend strongly on the concentration of the sodium carbonate catalyst. The have an interconnected bead structure similar to that of silica aerogels; bead sizes range from 30 to 130 {Angstrom}, and cell sizes are less than 0.1 {mu}m. We have achieved densities of 16 to 200 mg/cm{sup 3}. The RF foams can be pyrolyzed in an inert atmosphere to form a vitreous carbon foam (CRF), which has a similar microstructure but much higher mechanical strength. The PS/RF foams are obtained by filling the 2- to 3-{mu}m cells of PS foam (a low-density hydrocarbon foam we have developed) with RF. The resultant foams have the outstanding handling and machinability of the PS foam matrix and the small cell size of RF. Pyrolyzing PS/RF foams causes depolymerization and loss of the PS; the resulting CPR foams have a structure similar to the PS foams in which CRF both replicates and fills the PS cells.

  5. Low-density carbonized resorcinol-formaldehyde foams. Final report

    SciTech Connect

    Kong, F.M.; Buckley, S.R.; Giles, C.L. Jr.; Haendler, B.L.; Hair, L.M.; Letts, S.A.; Overturf, G.E. III; Price, C.W.; Cook, R.C.

    1991-07-04

    This report documents research and development on resorcinol- formaldehyde-based foam materials conducted between 1986 and June 1990, when the effort was discontinued. The foams discussed are resorcinol-formaldehyde (RF) foam, carbonized RF (CRF) foam, and two composite foams, a polystyrene/RF (PS/RF) foam and its carbonized derivative (CPR). The RF foams are synthesized by the polycondensation of resorcinol with formaldehyde in a slightly basic solution. Their structure and density depend strongly on the concentration of the sodium carbonate catalyst. The have an interconnected bead structure similar to that of silica aerogels; bead sizes range from 30 to 130 {Angstrom}, and cell sizes are less than 0.1 {mu}m. We have achieved densities of 16 to 200 mg/cm{sup 3}. The RF foams can be pyrolyzed in an inert atmosphere to form a vitreous carbon foam (CRF), which has a similar microstructure but much higher mechanical strength. The PS/RF foams are obtained by filling the 2- to 3-{mu}m cells of PS foam (a low-density hydrocarbon foam we have developed) with RF. The resultant foams have the outstanding handling and machinability of the PS foam matrix and the small cell size of RF. Pyrolyzing PS/RF foams causes depolymerization and loss of the PS; the resulting CPR foams have a structure similar to the PS foams in which CRF both replicates and fills the PS cells.

  6. Dietary and genetic effects on low-density lipoprotein heterogeneity.

    PubMed

    Krauss, R M

    2001-01-01

    We have tested whether differences in distribution and dietary responsiveness of low-density lipoprotein (LDL) subclasses contribute to the variability in the magnitude of LDL-cholesterol reduction induced by diets low in total and saturated fat and high in carbohydrate. Our studies have focused on a common, genetically influenced metabolic profile, characterized by a predominance of small, dense LDL particles (subclass pattern B), that is associated with a two- to threefold increase in risk for coronary artery disease. We have found that healthy normolipidemic individuals with this trait show a greater reduction in LDL cholesterol and particle number in response to low-fat, high-carbohydrate diets than do unaffected individuals (subclass pattern A). Moreover, such diets result in reduced LDL particle size, with induction of pattern B in a substantial proportion of pattern A men. Recent studies have indicated that this response is under genetic influence. Future identification of the specific genes involved may lead to improved targeting of dietary therapies aimed at reducing cardiovascular disease risk.

  7. Biologically active low density lipoprotein in human peripheral lymph.

    PubMed Central

    Reichl, D; Myant, N B; Brown, M S; Goldstein, J L

    1978-01-01

    We have compared the ability of human serum and peripheral lymph to suppress the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), to activate cholesteryl ester synthesis, and to compete with 125I-labeled low density lipoprotein (LDL) for binding to LDL receptors in cultured human fibroblasts. Whole lymph was active in all three tests and the activity per unit volume in lymph was approximately equal to 1/10th that in serum. All three biologic activities in lymph were confined to the d less than 1.063 g/ml fraction. Whole lymph had no significant effect on HMG-CoA reductase activity in fibroblasts from a patient with homozygous familial hypercholesterolemia, whose cells lack LDL receptors. The LDL-like biologic activity per unit mass of immunologically active apoprotein B was approximately the same in lymph as in serum. The current data indicate that functionally active LDL is present in lymph and that the concentration of this lipoprotein is approximately equal to 1/10th that in serum. PMID:201669

  8. Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages

    PubMed Central

    Atrahimovich, Dana; Khatib, Soliman; Sela, Shifra; Vaya, Jacob

    2016-01-01

    High levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100) that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25–4 μM). Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels. PMID:27516832

  9. Particle velocity and stress measurements in low density HMX

    SciTech Connect

    Sheffield, S.A.; Gustavsen, R.L.; Alcon, R.R.; Graham, R.A.; Anderson, M.U.

    1993-08-01

    Magnetic particle velocity gauges and PVDF stress rate gauges have been used to measure the shock response of low density HMX explosive (1.24 g/cm{sup 3}). In experiments done at LANL, magnetic particle velocity gauges were located on both sides of the explosive. In nearly identical experiments done at SNL, PVDF stress rate gauges were located at the same positions. Using these techniques both particle velocity and stress histories were obtained for a particular experimental condition. Loading and reaction paths were established in the stress-particle velocity plane for each input condition. This information was used to determine that compacted HMX has an impedance close to that of Kel-F and also that a global reaction rate of {approx} 0.13 {mu}s{sup {minus}1} was observed in HMX shocked to about 0.8 GPa. At low input stresses the transmitted wave profiles had long rise times (up to 1 {mu}s) due to the compaction processes.

  10. Modeling shock-driven reaction in low density PMDI foam

    NASA Astrophysics Data System (ADS)

    Brundage, Aaron; Alexander, C. Scott; Reinhart, William; Peterson, David

    Shock experiments on low density polyurethane foams reveal evidence of reaction at low impact pressures. However, these reaction thresholds are not evident over the low pressures reported for historical Hugoniot data of highly distended polyurethane at densities below 0.1 g/cc. To fill this gap, impact data given in a companion paper for polymethylene diisocyanate (PMDI) foam with a density of 0.087 g/cc were acquired for model validation. An equation of state (EOS) was developed to predict the shock response of these highly distended materials over the full range of impact conditions representing compaction of the inert material, low-pressure decomposition, and compression of the reaction products. A tabular SESAME EOS of the reaction products was generated using the JCZS database in the TIGER equilibrium code. In particular, the Arrhenius Burn EOS, a two-state model which transitions from an unreacted to a reacted state using single step Arrhenius kinetics, as implemented in the shock physics code CTH, was modified to include a statistical distribution of states. Hence, a single EOS is presented that predicts the onset to reaction due to shock loading in PMDI-based polyurethane foams. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's NNSA under Contract DE-AC04-94AL85000.

  11. Simulated Tip Rub Testing of Low-Density Metal Foam

    NASA Technical Reports Server (NTRS)

    Bowman, Cheryl L.; Jones, Michael G.

    2009-01-01

    Preliminary acoustic studies have indicated that low-density, open-cell, metal foams may be suitable acoustic liner material for noise suppression in high by-pass engines. Metal foam response under simulated tip rub conditions was studied to assess whether its durability would be sufficient for the foam to serve both as a rub strip above the rotor as well as an acoustic treatment. Samples represented four metal alloys, nominal cell dimensions ranging from 60 to 120 cells per inch (cpi), and relative densities ranging from 3.4 to 10 percent. The resulting rubbed surfaces were relatively smooth and the open cell structure of the foam was not adversely affected. Sample relative density appeared to have significant influence on the forces induced by the rub event. Acoustic responses of various surface preparations were measured using a normal incidence tube. The results of this study indicate that the foam s open-cell structure was retained after rubbing and that the acoustic absorption spectra variation was minimal.

  12. Low Density Lipid Nanoparticles for Solid Tumor Targeting

    PubMed Central

    Shrivastava, Mayank; Jain, Aviral; Gulbake, Arvind; Hurkat, Pooja; Jain, Neeti; Vijayraghwan, R.; Jain, Sanjay K.

    2014-01-01

    Abstract One of the most significant characteristics of cancer cells is their rapid dividing ability and overexpression of LDL receptors, which offers an opportunity for the selective targeting of these cells. 5-Fluorouracil (5-FU)-encapsulated low density lipid nanoparticles (LDLN) were prepared by the emulsion congealing method which mimics the plasma-derived LDL by acquiring the apolipoprotein B-100 from the blood. The average particle size, transmission electron microscope (TEM), and drug content of the prepared LDLN dispersion were found to be 161±3.5 nm, with spherical shape, and 0.370±0.05 mg/mL, respectively. In vitro release studies revealed a sustained profile which decreased with a lapse of time. In vivo studies of 5-FU serum concentration and biodistribution revealed a 5-FU serum concentration of 8.5% in tumor cells and about 2.1% in the liver at the end of 24 hr from LDLN. Tumor growth suppression studies showed 185.42% average tumor growth and 89.76% tumor height as compared to the control exhibiting tumor growth at 1166.47% and tumor height at 176.07%. On the basis of these collective data, it is suggested that a higher accumulation of LDLN, when given as an IV, in solid tumors is attributed to the active uptake of LDLN via LDL receptors via apolipoprotein B-100. PMID:26279976

  13. Novel Therapies for Low-Density Lipoprotein Cholesterol Reduction.

    PubMed

    Toth, Peter P

    2016-09-15

    Although many clinical trials and meta-analyses have demonstrated that lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with proportionately greater reductions in the risk of cardiovascular disease events, not all patients with hypercholesterolemia are able to attain risk-stratified LDL-C goals with statin monotherapy. Elucidation of the pathophysiology of genetic disorders of lipid metabolism (e.g., familial hypercholesterolemia) has led to the development of several novel lipid-lowering strategies, including blocking the degradation of hepatic LDL-C receptors that are important in LDL-C clearance, or the inhibition of apoprotein synthesis and lipidation. Mipomersen and lomitapide are highly efficacious new agents available for the treatment of patients with homozygous familial hypercholesterolemia. The recent introduction of PCSK9 inhibitors (alirocumab and evolocumab) have made it possible for many patients to achieve very low LDL-C concentrations (e.g., <40 mg/dl) that are usually not attainable with statin monotherapy. Ongoing clinical trials are examining the impact of very low LDL-C levels on cardiovascular disease event rates and the long-term safety of this approach. PMID:27620356

  14. Drift load in populations of small size and low density.

    PubMed

    Willi, Y; Griffin, P; Van Buskirk, J

    2013-03-01

    According to theory, drift load in randomly mating populations is determined by past population size, because enhanced genetic drift in small populations causes accumulation and fixation of recessive deleterious mutations of small effect. In contrast, segregating load due to mutations of low frequency should decline in smaller populations, at least when mutations are highly recessive and strongly deleterious. Strong local selection generally reduces both types of load. We tested these predictions in 13 isolated, outcrossing populations of Arabidopsis lyrata that varied in population size and plant density. Long-term size was estimated by expected heterozygosity at 20 microsatellite loci. Segregating load was assessed by comparing performance of offspring from selfings versus within-population crosses. Drift load was the heterosis effect created by interpopulation outbreeding. Results showed that segregating load was unrelated to long-term size. However, drift load was significantly higher in populations of small effective size and low density. Drift load was mostly expressed late in development, but started as early as germination and accumulated thereafter. The study largely confirms predictions of theory and illustrates that mutation accumulation can be a threat to natural populations.

  15. Low-Density Aerodynamics of the Stardust Sample Return Capsule

    NASA Technical Reports Server (NTRS)

    Wilmoth, Richard G.; Mitcheltree, Robert A.; Moss, James N.

    1997-01-01

    The aerodynamics of the Stardust Sample Return Capsule are analyzed in the low- density, transitional flow regime using free-molecular, Direct Simulation Monte Carlo, Navier-Stokes, and Newtonian methods to provide inputs for constructing a transitional flow bridging relation. The accuracy of this bridging relation in reconstructing the aero- dynamic coefficients given by the more exact methods is presented for a range of flight conditions and vehicle attitudes. There is good agreement between the various prediction methods, and a simple sine-squared bridging relation is shown to provide a reasonably good description of the axial force, normal force, and pitching moment over a range of Knudsen numbers from 0.001 to 10. The predictions show a static instability of the Star- dust capsule in the free-molecular regime that persists well into the transitional flow. The addition of a thin disk to the base of the capsule is shown to remove this static instability. However, the extremely high entry velocity of 12.6 km/s for the proposed trajectory introduces difficult design issues for incorporating this disk caused by the high aerothermal loads that occur even under relatively rarefied conditions.

  16. Alcohol alters low density lipoprotein composition and metabolism

    SciTech Connect

    Hoinacki, J.; Brown, J.; Dawson, M.; Deschenes, R.; Mulligan, J. )

    1991-03-11

    Two separate studies were conducted to examine the effect of ethanol (EtOH) dose on atherogenic low density lipoprotein (LDL) subfractions and LDL metabolism in vivo. In the first study, male, atherosclerosis-susceptible squirrel monkeys were divided in three treatments: controls fed liquid diet, and low and high alcohol groups given liquid diet with vodka substituted for carbohydrate at 12% and 24% of calories, respectively. After 6 months, LDL subclasses (LDL{sub 1a}, LDL{sub 1b} and LDL{sub 2}) were isolated by density gradient ultracentrifugation and polyacrylamide gradient gel electrophoresis, and their lipid and protein composition was determined. Low dose EtOH had no effect on LDL subfraction distribution while 24% EtOH resulted in an increase in the larger (LDL{sub 1a} and LDL{sub 1b}), buoyant subspecies without affecting the level of the more atherogenic, smaller, denser LDL{sub 2} particles. In the second study, {sup 125}I-LDL apolipoprotein B (apo B) was injected intravenously into Control and High EtOH monkeys and kinetic analyses were performed. Although the absolute catabolic rate (LDL production) was not altered, High EtOH primates showed a reduction in the fractional catabolic rate and a longer LDL apoB residence time.

  17. Covalent attachment of lactase to low-density polyethylene films.

    PubMed

    Goddard, J M; Talbert, J N; Hotchkiss, J H

    2007-01-01

    Polymer films to which bioactive compounds such as enzymes are covalently attached offer potential for in-package processing of food. Beta-galactosidase (lactase) was covalently attached to surface-functionalized low-density polyethylene films. A two-step wet chemical functionalization introduced 15.7 nmol/cm2 primary amines to the film surface. Contact angle, dye assays, X-ray photoelectron spectroscopy, and appropriate protein assays were used to characterize changes in film surface chemistry after each step in the process of attachment. Glutaraldehyde was used to covalently attach lactase to the surface at a density of 6.0 microg protein per cm2 via reductive amination. The bond between the covalently attached lactase and the functionalized polyethylene withstood heat treatment in the presence of an ionic denaturant with 74% enzyme retention, suggesting that migration of the enzyme into the food product would be unlikely. The resulting polyethylene had an enzyme activity of 0.020 lactase units (LU)/cm2 (approximately 4500 LU/g). These data suggest that enzymes that may have applications in foods can be covalently attached to inert polymer surfaces, retain significant activity, and thus have potential as a nonmigratory active packaging materials.

  18. Optimizing the bulk modulus of low-density cellular networks.

    PubMed

    Durand, Marc

    2005-07-01

    We present an alternative derivation of upper-bounds for the bulk modulus of both two-dimensional and three-dimensional cellular materials. For two-dimensional materials, we recover exactly the expression of the Hashin-Shtrikman (HS) upper-bound in the low-density limit, while for three-dimensional materials we even improve the HS bound. Furthermore, we establish necessary and sufficient conditions on the cellular structure for maximizing the bulk modulus, for a given solid volume fraction. The conditions are found to be exactly those under which the electrical (or thermal) conductivity of the material reaches its maximal value as well. These results provide a set of straightforward criteria allowing us to address the design of optimized cellular materials, and shed light on recent studies of structures with both maximal bulk modulus and maximal conductivity. Finally, we discuss the specific case of spring networks, and analyze the compatibility of the criteria presented here with the geometrical constraints caused by minimization of surface energy in a real foam.

  19. Development of Low Density Flexible Carbon Phenolic Ablators

    NASA Technical Reports Server (NTRS)

    Stackpole, Mairead; Thornton, Jeremy; Fan, Wendy; Agrawal, Parul; Doxtad, Evan; Gasch, Matt

    2011-01-01

    Phenolic Impregnated Carbon Ablator (PICA) was the enabling TPS material for the Stardust mission where it was used as a single piece heatshield. PICA has the advantages of low density (0.27g/cm3) coupled with efficient ablative capability at high heat fluxes. Under the Orion program, PICA was also shown to be capable of both ISS and lunar return missions however some unresolved issues remain for its application in a tiled configuration for the Orion-specific design. In particular, the problem of developing an appropriate gap filler resulted in the Orion program selecting AVCOAT as the primary heatshield material over PICA. We are currently looking at alternative architectures to yield flexible and more conformal carbon phenolic materials with comparable densities to PICA that will address some of the design issues faced in the application of a tiled PICA heat shield. These new materials are viable TPS candidates for upcoming NASA missions and as material candidates for private sector Commercial Orbital Transportation Services (COTS). This presentation will discuss flexible alternatives to PICA and include preliminary mechanical and thermal properties as well as arc jet and LHMEL screening test results.

  20. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Low-density lipoprotein immunological test system... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density...

  1. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Low-density lipoprotein immunological test system... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density...

  2. Bonding Low-density Nanoporous Metal Foams Using Sputtered Solder

    SciTech Connect

    Bono, M; Cervantes, O; Akaba, C; Hamza, A; Foreman, R; Teslich, N

    2007-08-21

    A method has been developed for bonding low-density nanoporous metal foam components to a substrate using solder that is sputtered onto the surfaces. Metal foams have unusual properties that make them excellent choices for many applications, and as technologies for processing these materials are evolving, their use in industry is increasing dramatically. Metal foams are lightweight and have advantageous dynamic properties, which make them excellent choices for many structural applications. They also provide good acoustic damping, low thermal conductivity, and excellent energy absorption characteristics. Therefore, these materials are commonly used in the automotive, aerospace, construction, and biomedical industries. The synthesis of nanoporous metal foams with a cell size of less then 1 {micro}m is an emerging technology that is expected to lead to widespread application of metal foams in microdevices, such as sensors and actuators. One of the challenges to manufacturing components from metal foams is that they can be difficult to attach to other structures without degrading their properties. For example, traditional liquid adhesives cannot be used because they are absorbed into foams. The problem of bonding or joining can be particularly difficult for small-scale devices made from nanoporous foam, due to the requirement for a thin bond layer. The current study addresses this problem and develops a method of soldering a nanoporous metal foam to a substrate with a bond thickness of less than 2 {micro}m. There are many applications that require micro-scale metal foams precisely bonded to substrates. This study was motivated by a physics experiment that used a laser to drive a shock wave through an aluminum foil and into a copper foam, in order to determine the speed of the shock in the copper foam. To avoid disturbing the shock, the interface between the copper foam and the aluminum substrate had to be as thin as possible. There are many other applications that

  3. Hypercholesterolemia, low density lipoprotein receptor and proprotein convertase subtilisin/kexin-type 9

    PubMed Central

    Gu, Hong-mei; Zhang, Da-wei

    2015-01-01

    Abstract Atherosclerotic cardiovascular disease is the main cause of mortality and morbidity in the world. Plasma levels of low density lipoprotein cholesterol (LDL-C) are positively correlated with the risk of atherosclerosis. High plasma LDL concentrations in patients with hypercholesterolemia lead to build-up of LDL in the inner walls of the arteries, which becomes oxidized and promotes the formation of foam cells, consequently initiating atherosclerosis. Plasma LDL is mainly cleared through the LDL receptor (LDLR) pathway. Mutations in the LDLR cause familiar hypercholesterolemia and increase the risk of premature coronary heart disease. The expression of LDLR is regulated at the transcriptional level via the sterol regulatory element binding protein 2 (SREBP-2) and at the posttranslational levels mainly through proprotein convertase subtilisin/kexin-type 9 (PCSK9) and inducible degrader of the LDLR (IDOL). In this review, we summarize the latest advances in the studies of PCSK9. PMID:26445568

  4. Theoretical prediction of low-density hexagonal ZnO hollow structures

    NASA Astrophysics Data System (ADS)

    Tuoc, Vu Ngoc; Huan, Tran Doan; Thao, Nguyen Thi; Tuan, Le Manh

    2016-10-01

    Along with wurtzite and zinc blende, zinc oxide (ZnO) has been found in a large number of polymorphs with substantially different properties and, hence, applications. Therefore, predicting and synthesizing new classes of ZnO polymorphs are of great significance and have been gaining considerable interest. Herein, we perform a density functional theory based tight-binding study, predicting several new series of ZnO hollow structures using the bottom-up approach. The geometry of the building blocks allows for obtaining a variety of hexagonal, low-density nanoporous, and flexible ZnO hollow structures. Their stability is discussed by means of the free energy computed within the lattice-dynamics approach. Our calculations also indicate that all the reported hollow structures are wide band gap semiconductors in the same fashion with bulk ZnO. The electronic band structures of the ZnO hollow structures are finally examined in detail.

  5. 99mTc-low density lipoprotein: intracellularly trapped radiotracer for noninvasive imaging of low density lipoprotein metabolism in vivo.

    PubMed

    Vallabhajosula, S; Goldsmith, S J

    1990-01-01

    Low density lipoprotein (LDL) is the major transport protein for endogenous cholesterol in human plasma. LDL can be radiolabeled with 99mTc using sodium dithionite as a reducing agent. Biodistribution studies of 99mTc-LDL in normal rabbits confirm that 99mTc-LDL acts as an intracellularly "trapped ligand" similar to radioiodinated tyramine cellobiose-LDL (the previously validated trapped radioligand). In addition, studies performed in hypercholesterolemic rabbit models demonstrated the feasibility of imaging hepatic LDL-receptor concentration noninvasively. 99mTc-LDL imaging studies in a number of hypercholesterolemic and hypocholesterolemic patients have proven useful in understanding the abnormal uptake and metabolism of LDL. In patients with hypercholesterolemia (HC), 99mTc-LDL appears to be taken up well by the actively evolving atherosclerotic lesions and xanthomata that contained foam cells and macrophages. In patients with myeloproliferative disease and chronic hypocholesterolemia, 99mTc-LDL images showed intense accumulation of radioactivity in the spleen and bone marrow; this demonstrated extensive proliferation of the macrophage population suggesting that hypocholesterolemia in these patients may be due to increased uptake of LDL uptake by the macrophages. 99mTc-LDL is a powerful tool for the noninvasive exploration of a variety of disorders of lipoprotein metabolism in patients.

  6. Development of Low Density Titanium Alloys for Structural Applications

    NASA Technical Reports Server (NTRS)

    Froes, F. H.; Suryanarayana, C.; Powell, C.; Ward-Close, C. Malcolm; Wilkes, D. M. J.

    1996-01-01

    In this report the results of a program designed to reduce the density of titanium by adding magnesium are presented. Because these two elements are immiscible under conventional ingot metallurgy techniques, two specialized powder metallurgy methods namely, mechanical alloying (MA) and physical vapor deposition (PVD) were implemented. The mechanical alloying experiments were done both at the University of Idaho and at the Defense Research Agency in UK. Since titanium is reactive with interstitial elements, a secondary goal of this research was to correlate solubility extensions with interstitial contamination content, especially oxygen and nitrogen. MA was carried out in SPEX 8000 shaker mils and different milling containers were utilized to control the level of contamination. Results showed that solubilities of Mg in Ti were obtained up to 28 at.% (16.4 wt. %) Mg in Ti for Ti-39.6 at. % (25 wt. %) Mg alloys, which greatly exceed those obtained under equilibrium conditions. This reflects a density reduction of approximately 26 %. Contamination of oxygen and nitrogen seemed to increase the solubility of magnesium in titanium in some cases; however, we were not able to make a clear correlation between contamination levels with solubilities. Work at the DRA has emphasized optimization of present PVD equipment, specifically composition and temperature control. Preliminary PVD data has shown Ti-Mg deposits have successfully been made up to 2 mm thick and that solubility extensions were achieved. The potential for density reduction of titanium by alloying with magnesium has been demonstrated; however, this work has only scratched the surface of the development of such low density alloys. Much research is needed before such alloys could be implemented into industry. Further funding is required in order to optimize the MA/PVD processes including contamination control, determination of optimal alloy compositions, microstructure development, and mechanical property

  7. Statins do not decrease small, dense low-density lipoprotein.

    PubMed

    Choi, Cheol Ung; Seo, Hong Seog; Lee, Eun Mi; Shin, Seung Yong; Choi, Un-Jung; Na, Jin Oh; Lim, Hong Euy; Kim, Jin Won; Kim, Eung Ju; Rha, Seung-Woon; Park, Chang Gyu; Oh, Dong Joo

    2010-01-01

    In an observational study, we examined the effect of statins on low-density-lipoprotein (LDL) subfractions.Using density-gradient ultracentrifugation, we measured small, dense LDL density in 612 patients (mean age, 61.7 ± 12.6 yr), some with and some without coronary artery disease, who were placed in a statin-treated group (n=172) or a control group (n=440) and subdivided on the basis of coronary artery disease status.Total cholesterol, LDL cholesterol, apolipoprotein B, and the LDL cholesterol/apolipoprotein B ratio were significantly lower in the statin group. However, the proportion of small, dense LDL was higher in the statin group (42.9% ± 9.5% vs 41.3% ± 8.5%; P=0.046) and the proportion of large, buoyant LDL was lower (23.6% ± 7.5% vs 25.4% ± 7.9%; P=0.011). In the statin group, persons without coronary artery disease had higher proportions of small, dense LDL, and persons with coronary artery disease tended to have higher proportions of small, dense LDL.Our study suggests that statin therapy--whether or not recipients have coronary artery disease--does not decrease the proportion of small, dense LDL among total LDL particles, but in fact increases it, while predictably reducing total LDL cholesterol, absolute amounts of small, dense LDL, and absolute amounts of large, buoyant LDL. If and when our observation proves to be reproducible in subsequent large-scale studies, it should provide new insights into small, dense LDL and its actual role in atherogenesis or the progression of atherosclerosis.

  8. Two Transiting Low Density Sub-Saturns from K2

    NASA Astrophysics Data System (ADS)

    Petigura, Erik A.; Howard, Andrew W.; Lopez, Eric D.; Deck, Katherine M.; Fulton, Benjamin J.; Crossfield, Ian J. M.; Ciardi, David R.; Chiang, Eugene; Lee, Eve J.; Isaacson, Howard; Beichman, Charles A.; Hansen, Brad M. S.; Schlieder, Joshua E.; Sinukoff, Evan

    2016-02-01

    We report the discovery and confirmation of K2-24 b and c, two sub-Saturn planets orbiting a bright (V = 11.3), metal-rich ([Fe/H] = 0.42 ± 0.04 dex) G3 dwarf in the K2 Campaign 2 field. The planets are 5.68 ± 0.56 {R}\\oplus and 7.82 ± 0.72 {R}\\oplus and have orbital periods of 20.8851 ± 0.0003 days and 42.3633 ± 0.0006 days, near the 2:1 mean-motion resonance. We obtained 32 radial velocities with Keck/HIRES and detected the reflex motion due to K2-24 b and c. These planets have masses of 21.0 ± 5.4 {M}\\oplus and 27.0 ± 6.9 {M}\\oplus , respectively. With low densities of 0.63 ± 0.25 g cm-3 and 0.31 ± 0.12 g cm-3, respectively, the planets require thick envelopes of H/He to explain their large sizes and low masses. Interior structure models predict that the planets have fairly massive cores of 17.6+/- 4.3 {M}\\oplus and 16.1+/- 4.2 {M}\\oplus , respectively. They may have formed exterior to their present locations, accreted their H/He envelopes at large orbital distances, and migrated in as a resonant pair. The proximity to resonance, large transit depths, and host star brightness offers rich opportunities for TTV follow-up. Finally, the low surface gravities of the K2-24 planets make them favorable targets for transmission spectroscopy by Hubble Space Telescope, Spitzer, and James Webb Space Telescope.

  9. Iron-ascorbate-phospholipid mediated modification of low density lipoprotein.

    PubMed

    Greenspan, P; Yu, H; Gutman, R L; Mao, F; Ryu, B H; Lou, P

    1996-06-11

    LDL can be oxidized by a variety of agents to form a modified lipoprotein which is capable of being avidly metabolized by macrophages. While previous in vitro studies have focused exclusively on the oxidation of LDL, other lipids found in the atheroma are also subject to oxidation and its lipoperoxide byproducts may contribute to the process of LDL modification. To examine the relationship between the oxidation of phospholipids and the subsequent modification of LDL, we incubated 250 microM phosphatidylcholine with 10 microM ferrous sulfate and 50 microM ascorbic acid in 10 mM Tris (pH 7.0). After 18 h at 37 degrees C, significant amounts of thiobarbituric acid reactive substances (TBARS) were formed. The inclusion of LDL (100 micrograms protein/ml) elevated the TBARS and increased the electrophoretic mobility of the lipoprotein. LDL treated with iron and ascorbate in the absence of phosphatidylcholine did not result in the modification of this lipoprotein. LDL that was incubated with phosphatidylcholine, iron and ascorbate was found to be metabolized by macrophages to a far greater extent than native LDL or LDL treated with phosphatidylcholine alone. Probucol (10 microM) inhibited the LDL modification process. These results demonstrate that while iron and ascorbate cannot oxidize LDL directly, the addition of phosphatidylcholine to these initiators of lipid peroxidation can mediate and lead to the modification of LDL. PMID:8664335

  10. The Conductor-Dielectric Junctions in a Low Density Plasma

    NASA Technical Reports Server (NTRS)

    Vayner, Boris; Galofaro, Joel; Ferguson, Dale; deGroot, Wim; Thomson, Clint; Dennison, J. R.; Davies, Robert

    1999-01-01

    chromic acid anodized aluminum plate immersed in low density argon and xenon plasmas. Analysis of these spectra confirms our earlier findings that aluminum atoms are ejected from the arc site. Moreover, it is found that chromium atoms are also quite abundant in the arc plasma. It is believed that the latter results contribute considerably to the understanding of processes of plasma contamination caused by arcing.

  11. Combining Ratio Estimation for Low Density Parity Check (LDPC) Coding

    NASA Technical Reports Server (NTRS)

    Mahmoud, Saad; Hi, Jianjun

    2012-01-01

    The Low Density Parity Check (LDPC) Code decoding algorithm make use of a scaled receive signal derived from maximizing the log-likelihood ratio of the received signal. The scaling factor (often called the combining ratio) in an AWGN channel is a ratio between signal amplitude and noise variance. Accurately estimating this ratio has shown as much as 0.6 dB decoding performance gain. This presentation briefly describes three methods for estimating the combining ratio: a Pilot-Guided estimation method, a Blind estimation method, and a Simulation-Based Look-Up table. The Pilot Guided Estimation method has shown that the maximum likelihood estimates of signal amplitude is the mean inner product of the received sequence and the known sequence, the attached synchronization marker (ASM) , and signal variance is the difference of the mean of the squared received sequence and the square of the signal amplitude. This method has the advantage of simplicity at the expense of latency since several frames worth of ASMs. The Blind estimation method s maximum likelihood estimator is the average of the product of the received signal with the hyperbolic tangent of the product combining ratio and the received signal. The root of this equation can be determined by an iterative binary search between 0 and 1 after normalizing the received sequence. This method has the benefit of requiring one frame of data to estimate the combining ratio which is good for faster changing channels compared to the previous method, however it is computationally expensive. The final method uses a look-up table based on prior simulated results to determine signal amplitude and noise variance. In this method the received mean signal strength is controlled to a constant soft decision value. The magnitude of the deviation is averaged over a predetermined number of samples. This value is referenced in a look up table to determine the combining ratio that prior simulation associated with the average magnitude of

  12. Reliability of Calculated Low-Density Lipoprotein Cholesterol.

    PubMed

    Meeusen, Jeffrey W; Snozek, Christine L; Baumann, Nikola A; Jaffe, Allan S; Saenger, Amy K

    2015-08-15

    Aggressive low-density lipoprotein cholesterol (LDL-C)-lowering strategies are recommended for prevention of cardiovascular events in high-risk populations. Guidelines recommend a 30% to 50% reduction in at-risk patients even when LDL-C concentrations are between 70 and 130 mg/dl (1.8 to 3.4 mmol/L). However, calculation of LDL-C by the Friedewald equation is the primary laboratory method for routine LDL-C measurement. We compared the accuracy and reproducibility of calculated LDL-C <130 mg/dl (3.4 mmol/L) to LDL-C measured by β quantification (considered the gold standard method) in 15,917 patients with fasting triglyceride concentrations <400 mg/dl (4.5 mmol/L). Both variation and bias of calculated LDL-C increased at lower values of measured LDL-C. The 95% confidence intervals for a calculated LDL-C of 70 mg/dl (1.8 mmol/L) and 30 mg/dl (0.8 mmol/L) were 60 to 86 mg/dl (1.6 to 2.2 mmol/L) and 24 to 60 mg/dl (0.6 to 1.6 mmol/L), respectively. Previous recommendations have emphasized the requirement for a fasting sample with triglycerides <400 mg/dl (4.5 mmol/L) to calculate LDL-C by the Friedewald equation. However, no recommendations have addressed the appropriate lower reportable limit for calculated LDL-C. In conclusion, calculated LDL-C <30 mg/dl (0.8 mmol/L) should not be reported because of significant deviation from the gold standard measured LDL-C results, and caution is advised when using calculated LDL-CF values <70 mg/dl (1.8 mmol/L) to make treatment decisions.

  13. Native low density lipoprotein promotes lipid raft formation in macrophages.

    PubMed

    Song, Jian; Ping, Ling-Yan; Duong, Duc M; Gao, Xiao-Yan; He, Chun-Yan; Wei, Lei; Wu, Jun-Zhu

    2016-03-01

    Oxidized low‑density lipoprotein (LDL) has an important role in atherogenesis; however, the mechanisms underlying cell‑mediated LDL oxidation remain to be elucidated. The present study investigated whether native‑LDL induced lipid raft formation, in order to gain further insight into LDL oxidation. Confocal microscopic analysis revealed that lipid rafts were aggregated or clustered in the membrane, which were colocalized with myeloperoxidase (MPO) upon native LDL stimulation; however, in the presence of methyl‑β‑cyclodextrin (MβCD), LDL‑stimulated aggregation, translocation, and colocalization of lipid rafts components was abolished.. In addition, lipid raft disruptors MβCD and filipin decreased malondialdehyde expression levels. Density gradient centrifugation coupled to label‑free quantitative proteomic analysis identified 1,449 individual proteins, of which 203 were significantly upregulated following native‑LDL stimulation. Functional classification of the proteins identified in the lipid rafts revealed that the expression levels of translocation proteins were upregulated. In conclusion, the results of the present study indicated that native‑LDL induced lipid raft clustering in macrophages, and the expression levels of several proteins were altered in the stimulated macrophages, which provided novel insights into the mechanism underlying LDL oxidation.

  14. Heterogeneity of plasma low-density lipoproteins and atherosclerosis risk.

    PubMed

    Krauss, R M

    1994-10-01

    Increased levels of IDL and small, dense LDL are associated with the risk of coronary artery disease. Possible mechanisms include increased susceptibility of small, dense LDL to oxidation, and to other pathologic effects, such as increased retention in the arterial wall. Beneficial effects of a low-fat diet and certain lipid-lowering therapies on the levels and properties of small, dense LDL or their precursors may contribute substantially to the reductions in coronary atherosclerosis observed in several lipid-lowering trials.

  15. Cellular uptake of a dexamethasone palmitate-low density lipoprotein complex by macrophages and foam cells.

    PubMed

    Tauchi, Yoshihiko; Chono, Sumio; Morimoto, Kazuhiro

    2003-04-01

    To evaluate the utility of a dexamethasone palmitate (DP)-low density lipoprotein (LDL) complex to transport drug into foam cells, the cellular uptake of DP-LDL complex by macrophages and foam cells was examined. The DP-LDL complex was prepared by incubation with DP and LDL, and the DP-LDL complex and murine macrophages were incubated. No cellular uptake of the DP-LDL complex by macrophages was found until 6 h after the start of incubation, but this gradually increased from 12 to 48 h. On the other hand, the cellular uptake of the oxidized DP-LDL complex was already apparent at 3 h after the start incubation, and then markedly increased until 48 h incubation along with that of the lipid emulsion (LE) containing DP (DP-LE). The cellular uptake of DP-LE by foam cells was significantly lower than that by macrophages. However, the cellular uptake of DP-LDL complex by foam cells was similar to that by macrophages. These findings suggest that the DP-LDL complex is oxidatively modified, and then incorporated into macrophages and foam cells through the scavenger receptor pathway. Since selective delivery of drugs into foam cells in the early stage of atherosclerosis is a useful protocol for antiatherosclerosis treatment, the DP-LDL complex appears to be a potentially useful drug-carrier complex for future antiatherosclerotic therapy.

  16. Macrophage uptake of low-density lipoprotein modified by 4-hydroxynonenal. An ultrastructural study

    SciTech Connect

    Hoff, H.F.; Cole, T.B. )

    1991-02-01

    We have documented the ultrastructural characteristics of the uptake and processing by mouse peritoneal macrophages (MPM) of low-density lipoprotein (LDL) modified with 4-hydroxynonenal (HNE), an intermediate of lipid peroxidation. This was performed as part of a larger biochemical study assessing the role of LDL oxidation in lipid loading of macrophages during atherogenesis. Gold-labeled LDL that was modified with HNE leading to particle aggregation represented the morphologic probe used. When incubated with MPM, the probe became associated with short segments of cell membrane, probably derived from blebs or from lysed cells. At 37 degrees C there was a time-dependent increase in uptake by MPM, and at 4 hours the increase paralleled the degradation by MPM of 125I-labeled HNE-LDL-cAu. Clathrin-coated pits on the cell surface were consistently associated with probe. Uptake of probe appeared to occur via phagocytosis, because pseudopods frequently surrounded probe, and cytochalasin D quantitatively prevented probe uptake. A time-dependent increase was found in the number of gold particles per unit area within vacuoles, some of which were secondary lysosomes, based on acid phosphatase-positive staining. Thus, HNE-induced aggregation of LDL during oxidation, binding of aggregates to clathrin-coated pits on MPM, and subsequent phagocytosis may represent one of the ways lipid-laden foam cells are formed in vivo.

  17. Explosively driven low-density foams and powders

    DOEpatents

    Viecelli, James A.; Wood, Lowell L.; Ishikawa, Muriel Y.; Nuckolls, John H.; Pagoria, Phillip F.

    2010-05-04

    Hollow RX-08HD cylindrical charges were loaded with boron and PTFE, in the form of low-bulk density powders or powders dispersed in a rigid foam matrix. Each charge was initiated by a Comp B booster at one end, producing a detonation wave propagating down the length of the cylinder, crushing the foam or bulk powder and collapsing the void spaces. The PdV work done in crushing the material heated it to high temperatures, expelling it in a high velocity fluid jet. In the case of boron particles supported in foam, framing camera photos, temperature measurements, and aluminum witness plates suggest that the boron was completely vaporized by the crush wave and that the boron vapor turbulently mixed with and burned in the surrounding air. In the case of PTFE powder, X-ray photoelectron spectroscopy of residues recovered from fragments of a granite target slab suggest that heating was sufficient to dissociate the PTFE to carbon vapor and molecular fluorine which reacted with the quartz and aluminum silicates in the granite to form aluminum oxide and mineral fluoride compounds.

  18. Studies on epitopes on low-density lipoprotein modified by 4-hydroxynonenal. Biochemical characterization and determination.

    PubMed Central

    Chen, Q; Esterbauer, H; Jürgens, G

    1992-01-01

    Oxidation of human low-density lipoprotein (LDL) was found to be accompanied by the generation of various reactive aldehydes. One of them, 4-hydroxynonenal (HNE), was shown to modify LDL to a form which represents a good model of oxidized LDL (ox-LDL). In order to investigate the epitopes newly formed on HNE-modified LDL, a polyvalent antiserum to HNE-LDL [anti-(HNE-LDL)] was raised in rabbits and the non-specific components were removed with native LDL coupled to CNBr-Sepharose 4B. Competitive fluorescence immunoassay analysis showed that anti-(HNE-LDL) recognized HNE-LDL, copper-oxidized LDL, HNE-albumin and to a lower extent HNE-modified high-density lipoprotein 3 (HNE-HDL3) and ox-HDL3 but not native LDL. A certain degree of cross-reactivity of the antibody with LDLs modified by either hexanal or 2,4-heptadienal was found. No reaction was obtained with LDL labelled with malondialdehyde. From the abilities of HNE-modified poly(L-amino acids) to compete with HNE-LDL for binding to anti-(HNE-LDL), it is postulated that lysine, tyrosine, arginine and histidine are involved in the formation of HNE-derived epitopes on apolipoprotein B (apo B). Using a double-sandwich fluorescence immunoassay [capture antibody: anti-(apo B); detection antibody: anti-(HNE-LDL)] we found that the HNE-derived epitopes were expressed at a far higher degree in ox-LDL and HNE-LDL than in native LDL. PMID:1280111

  19. Fabrication of very-low-density, high-stiffness carbon fiber/aluminum hybridized composite with ultra-low density and high stiffness (M-11)

    NASA Technical Reports Server (NTRS)

    Suzuki, Tomoo

    1993-01-01

    Fabrication of a composite material with ultra-low density and high stiffness in microgravity is the objective of the investigation. The composite structure to be obtained is a random three-dimensional array of high modulus, short carbon fibers bonded at contact points by an aluminum alloy coated on the fibers. The material is highly porous and thus has a very low density. The motivation toward the investigation, simulation experiments, choice of the component materials, and on-flight experiment during ballistic trajectory of a NASDA rocket, are described.

  20. Increased low density lipoprotein degradation in aorta of irradiated mice is inhibited by preenrichment of low density lipoprotein with alpha-tocopherol.

    PubMed

    Tribble, D L; Krauss, R M; Chu, B M; Gong, E L; Kullgren, B R; Nagy, J O; La Belle, M

    2000-10-01

    We previously reported that upper thoracic exposure to ionizing radiation (IR) accelerates fatty streak formation in C57BL/6 mice and that such effects are inhibited by overexpression of the antioxidant enzyme CuZn-superoxide dismutase (SOD). Notably, IR-accelerated lesion formation is strictly dependent on a high fat diet (i.e., atherogenic lipoproteins) but does not involve alterations in circulating lipid or lipoprotein levels. We thus proposed that IR promotes changes in the artery wall that enhance the deposition of lipoprotein lipids. To address this hypothesis, we examined the effects of IR on aortic accumulation and degradation of low density lipoproteins (LDL). Ten-week-old C57BL/6 mice were exposed to a single (8-Gy) dose of (60)Co radiation to the upper thoracic area or were sham irradiated (controls) and were then placed on the high fat diet. Five days postexposure, the mice received either (125)I-labeled LDL ((125)I-LDL) (which was used to measure intact LDL) or (125)I-labeled tyramine cellobiose ((125)I-TC)-LDL (which was used to measure both intact and cell-degraded LDL) via tail vein injection. On the basis of trichloroacetic acid (TCA)-precipitable counts in retroorbital blood samples, > or =95% of donor LDL was cleared within 24 h and there were no differences in time-averaged plasma concentrations of the two forms of LDL among irradiated and control mice. Aortic values increased markedly within the first hour and thereafter exhibited a slow increase up to 24 h. There were no differences between irradiated and control mice at 1 h, when values primarily reflected LDL entry, but a divergence was observed thereafter. At 24 h, (125)I-TC-associated counts were 1.8-fold higher in irradiated mice (P = 0.10). In contrast, (125)I-LDL-associated counts were 30% lower in irradiated mice (P< 0.05), suggesting that most of the retained (125)I-TC was associated with LDL degradation products. Consistent with the proposed involvement of oxidative or redox

  1. Aggregation and fusion of low-density lipoproteins in vivo and in vitro

    PubMed Central

    Gursky, Olga

    2014-01-01

    Low-density lipoproteins (LDLs, also known as ‘bad cholesterol’) are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of LDL-derived lipid droplets in the arterial wall. According to the widely accepted ‘response-to-retention hypothesis’, LDL binding to the extracellular matrix proteoglycans in the arterial intima induces hydrolytic and oxidative modifications that promote LDL aggregation and fusion. This enhances LDL uptake by the arterial macrophages and triggers a cascade of pathogenic responses that culminate in the development of atherosclerotic lesions. Hence, LDL aggregation, fusion, and lipid droplet formation are important early steps in atherogenesis. In vitro, a variety of enzymatic and nonenzymatic modifications of LDL can induce these reactions and thereby provide useful models for their detailed analysis. Here, we summarize current knowledge of the in vivo and in vitro modifications of LDLs leading to their aggregation, fusion, and lipid droplet formation; outline the techniques used to study these reactions; and propose a molecular mechanism that underlies these pro-atherogenic processes. Such knowledge is essential in identifying endogenous and exogenous factors that can promote or prevent LDL aggregation and fusion in vivo and to help establish new potential therapeutic targets to decelerate or even block these pathogenic reactions. PMID:25197325

  2. Biodegradation of low-density polyethylene (LDPE) by isolated fungi in solid waste medium

    SciTech Connect

    Zahra, Sahebnazar; Abbas, Shojaosadati Seyed; Mahsa, Mohammad-Taheri; Mohsen, Nosrati

    2010-03-15

    In this study, biodegradation of low-density polyethylene (LDPE) by isolated landfill-source fungi was evaluated in a controlled solid waste medium. The fungi, including Aspergillus fumigatus, Aspergillus terreus and Fusarium solani, were isolated from samples taken from an aerobic aged municipal landfill in Tehran. These fungi could degrade LDPE via the formation of a biofilm in a submerged medium. In the sterilized solid waste medium, LPDE films were buried for 100 days in a 1-L flask containing 400 g sterile solid waste raw materials at 28 deg. C. Each fungus was added to a separate flask. The moisture content and pH of the media were maintained at the optimal levels for each fungus. Photo-oxidation (25 days under UV-irradiation) was used as a pretreatment of the LDPE samples. The progress of the process was monitored by measurement of total organic carbon (TOC), pH, temperature and moisture. The results obtained from monitoring the process using isolated fungi under sterile conditions indicate that these fungi are able to grow in solid waste medium. The results of FT-IR and SEM analyses show that A. terreus and A. fumigatus, despite the availability of other organic carbon of materials, could utilize LDPE as carbon source. While there has been much research in the field of LDPE biodegradation under solid conditions, this is the first report of degradation of LDPE by A. fumigatus.

  3. Chitosan-modified carbon nanotubes-based platform for low-density lipoprotein detection.

    PubMed

    Ali, Md Azahar; Singh, Nawab; Srivastava, Saurabh; Agrawal, Ved V; John, Renu; Onoda, M; Malhotra, Bansi D

    2014-10-01

    We have fabricated an immunosensor based on carbon nanotubes and chitosan (CNT-CH) composite for detection of low density lipoprotein (LDL) molecules via electrochemical impedance technique. The CNT-CH composite deposited on indium tin oxide (ITO)-coated glass electrode has been used to covalently interact with anti-apolipoprotein B (antibody: AAB) via a co-entrapment method. The biofunctionalization of AAB on carboxylated CNT-CH surface has been confirmed by Fourier transform infrared spectroscopic and electron microscopic studies. The covalent functionalization of antibody on transducer surface reveals higher stability and reproducibility of the fabricated immunosensor. Electrochemical properties of the AAB/CNT-CH/ITO electrode have been investigated using cyclic voltammetric and impedimetric techniques. The impedimetric response of the AAB/CNT-CH/ITO immunoelectrode shows a high sensitivity of 0.953 Ω/(mg/dL)/cm(2) in a detection range of 0-120 mg/dL and low detection limit of 12.5 mg/dL with a regression coefficient of 0.996. The observed low value of association constant (0.34 M(-1)s(-1)) indicates high affinity of AAB/CNT-CH/ITO immunoelectrode towards LDL molecules. This fabricated immunosensor allows quantitative estimation of LDL concentration with distinguishable variation in the impedance signal.

  4. The behavior of high-purity, low-density air plasma sprayed thermal barrier coatings

    SciTech Connect

    Helminiak, Yanar NM

    2009-12-01

    Research on the behavior of high-purity, low-density (85%) air plasma sprayed (APS) thermal barrier coatings (TBC) with NiCoCrAlY bond coats deposited by argon-shrouded plasma spraying is described. The microstructure of the APS topcoats is one variable in this study intended to maximize the coating thicknesses that can be applied without spallation and to minimize the thermal conduction through the YSZ layer. The specimens were evaluated using cyclic oxidation tests and important properties of the TBCs, such as resistance to sintering and phase transformation, were determined. The high purity resulted in top coats which are highly resistant to sintering and transformation from the metastable tetragonal phase to the equilibrium mixture of monoclinic and cubic phases. The porous topcoat microstructure also resulted in significant durability during thermal cycling. The actual failure mechanisms of the APS coatings were found to depend on topcoat thickness, CTE of the superalloy substrate and the nature of the thermal exposure.

  5. Melt index of low-density polyethylene and its effect on rotational molding

    NASA Astrophysics Data System (ADS)

    Yuldashev, A. Kh.; Negmatov, S. S.; Abed-Negmatova, N. S.; Abdurakhmanov, A. G.; Bozorov, Sh. A.; Eminov, Sh. Sh.; Aripova, A.; Khodjikariev, D. M.

    2012-07-01

    The melt index of low density polyethylene is directly correlated to the "in service" strength. This correlation together with other chemical properties allowed us to select the best material for rotational molding process.

  6. Fluorocarbon seal replaces metal piston ring in low density gas environment

    NASA Technical Reports Server (NTRS)

    Morath, W. D.; Morgan, N. E.

    1967-01-01

    Reinforced fluorocarbon cupseal, which provides an integral lip-type seal, replaces the metal piston rings in piston-cylinder configurations used in the compression of low density gases. The fluorocarbon seal may be used as cryogenic compressor piston seals.

  7. Measurement of low-density lipoprotein cholesterol in assessment and management of cardiovascular disease risk.

    PubMed

    Jialal, I; Remaley, A T

    2014-07-01

    The deposition of cholesterol in the arterial wall by the infiltration of low-density lipoproteins (LDLs) is a key step in the development of atherosclerosis. In this Commentary, we discuss recent recommendations for clinical laboratory measurement of low-density lipoprotein cholesterol (LDL-C) and its utility both for assessing cardiovascular disease risk and as a tool in the management of patients receiving lipid-lowering therapy.

  8. Method and composition for molding low density desiccant syntactic foam articles

    DOEpatents

    Lula, James W.; Schicker, James R.

    1984-01-01

    A method and a composition are provided for molding low density desiccant syntactic foam articles. A low density molded desiccant article may be made as a syntactic foam by blending a thermosetting resin, microspheres and molecular sieve desiccant powder, molding and curing. Such articles have densities of 0.2-0.9 g/cc, moisture capacities of 1-12% by weight, and can serve as light weight structural supports.

  9. Method of Error Floor Mitigation in Low-Density Parity-Check Codes

    NASA Technical Reports Server (NTRS)

    Hamkins, Jon (Inventor)

    2014-01-01

    A digital communication decoding method for low-density parity-check coded messages. The decoding method decodes the low-density parity-check coded messages within a bipartite graph having check nodes and variable nodes. Messages from check nodes are partially hard limited, so that every message which would otherwise have a magnitude at or above a certain level is re-assigned to a maximum magnitude.

  10. Protection by polyphenols of postprandial human plasma and low-density lipoprotein modification: the stomach as a bioreactor.

    PubMed

    Kanner, Joseph; Gorelik, Shlomit; Roman, Sirota; Kohen, Ron

    2012-09-12

    Recent studies dramatically showed that the removal of circulating modified low-density lipoprotein (LDL) results in complete prevention of atherosclerosis. The gastrointestinal tract is constantly exposed to food, some of it containing oxidized compounds. Lipid oxidation in the stomach was demonstrated by ingesting heated red meat in rats. Red wine polyphenols added to the rats' meat diet prevented lipid peroxidation in the stomach and absorption of malondialdehyde (MDA) in rat plasma. In humans, postprandial plasma MDA levels rose by 3-fold after a meal of red meat cutlets. MDA derived from meat consumption caused postprandial plasma LDL modification in human. The levels of plasma MDA showed a 75% reduction by consumption of red wine polyphenols during the meat meal. Locating the main biological site of action of polyphenols in the stomach led to a revision in the understanding of how antioxidants work in vivo and may help to elucidate the mechanism involved in the protective effects of polyphenols in human health.

  11. Esterification of Low Density Lipoprotein Cholesterol in Human Fibroblasts and Its Absence in Homozygous Familial Hypercholesterolemia

    PubMed Central

    Goldstein, Joseph L.; Dana, Suzanna E.; Brown, Michael S.

    1974-01-01

    A new mechanism is described for the cellular esterification of cholesterol derived from extra-cellular lipoproteins. Incubation of monolayers of cultured fibroblasts from normal human subjects with low density lipoproteins led to a 30- to 40-fold increase in the rate of incorporation of either [14C]acetate or [14C]oleate into the fatty acid fraction of cholesteryl [14C]esters. This stimulation of cholesteryl ester formation by low density lipoproteins occurred despite the fact that endogenous synthesis of free cholesterol was completely suppressed by the lipoprotein. Thus, exogenous cholesterol contained in low density lipoproteins, rather than endogenously synthesized sterol, appeared to provide the cholesterol substrate for this cellular esterfication process. High density lipoproteins and the lipoprotein-deficient fraction of serum neither stimulated cholesteryl ester formation nor inhibited cholesterol synthesis. Both the low density lipoprotein-dependent increase in cholesterol esterification and decrease in free cholesterol synthesis required the interaction of the lipoprotein with its recently described cell surface receptor. Cells from homozygotes with familial hypercholesterolemia, which lack specific low density lipoprotein receptors, showed neither lipoprotein-dependent cholesterol esterification nor suppression of cholesterol synthesis. The reciprocal changes in free cholesterol synthesis and cholesteryl ester formation produced by low density lipoprotein-receptor interactions may play an important role in the regulation of the cholesterol content of mammalian cells. PMID:4373706

  12. Esterification of low density lipoprotein cholesterol in human fibroblasts and its absence in homozygous familial hypercholesterolemia.

    PubMed

    Goldstein, J L; Dana, S E; Brown, M S

    1974-11-01

    A new mechanism is described for the cellular esterification of cholesterol derived from extra-cellular lipoproteins. Incubation of monolayers of cultured fibroblasts from normal human subjects with low density lipoproteins led to a 30- to 40-fold increase in the rate of incorporation of either [(14)C]acetate or [(14)C]oleate into the fatty acid fraction of cholesteryl [(14)C]esters. This stimulation of cholesteryl ester formation by low density lipoproteins occurred despite the fact that endogenous synthesis of free cholesterol was completely suppressed by the lipoprotein. Thus, exogenous cholesterol contained in low density lipoproteins, rather than endogenously synthesized sterol, appeared to provide the cholesterol substrate for this cellular esterfication process. High density lipoproteins and the lipoprotein-deficient fraction of serum neither stimulated cholesteryl ester formation nor inhibited cholesterol synthesis. Both the low density lipoprotein-dependent increase in cholesterol esterification and decrease in free cholesterol synthesis required the interaction of the lipoprotein with its recently described cell surface receptor. Cells from homozygotes with familial hypercholesterolemia, which lack specific low density lipoprotein receptors, showed neither lipoprotein-dependent cholesterol esterification nor suppression of cholesterol synthesis. The reciprocal changes in free cholesterol synthesis and cholesteryl ester formation produced by low density lipoprotein-receptor interactions may play an important role in the regulation of the cholesterol content of mammalian cells.

  13. Improving GLOBALlAND30 Artificial Type Extraction Accuracy in Low-Density Residents

    NASA Astrophysics Data System (ADS)

    Hou, Lili; Zhu, Ling; Peng, Shu; Xie, Zhenlei; Chen, Xu

    2016-06-01

    GlobalLand 30 is the first 30m resolution land cover product in the world. It covers the area within 80°N and 80°S. There are ten classes including artificial cover, water bodies, woodland, lawn, bare land, cultivated land, wetland, sea area, shrub and snow,. The TM imagery from Landsat is the main data source of GlobalLand 30. In the artificial surface type, one of the omission error happened on low-density residents' part. In TM images, hash distribution is one of the typical characteristics of the low-density residents, and another one is there are a lot of cultivated lands surrounded the low-density residents. Thus made the low-density residents part being blurred with cultivated land. In order to solve this problem, nighttime light remote sensing image is used as a referenced data, and on the basis of NDBI, we add TM6 to calculate the amount of surface thermal radiation index TR-NDBI (Thermal Radiation Normalized Difference Building Index) to achieve the purpose of extracting low-density residents. The result shows that using TR-NDBI and the nighttime light remote sensing image are a feasible and effective method for extracting low-density residents' areas.

  14. Increased uptake of alpha-hydroxy aldehyde-modified low density lipoprotein by macrophage scavenger receptors.

    PubMed

    Kawamura, M; Heinecke, J W; Chait, A

    2000-07-01

    Reactive aldehydes can be formed during the oxidation of lipids, glucose, and amino acids and during the nonenzymatic glycation of proteins. Low density lipoprotein (LDL) modified with malondialdehyde are taken up by scavenger receptors on macrophages. In the current studies we determined whether alpha-hydroxy aldehydes also modify LDL to a form recognized by macrophage scavenger receptors. LDL modified by incubation with glycolaldehyde, glyceraldehyde, erythrose, arabinose, or glucose (alpha-hydroxy aldehydes that possess two, three, four, five, and six carbon atoms, respectively) exhibited decreased free amino groups and increased mobility on agarose gel electrophoresis. The lower the molecular weight of the aldehyde used for LDL modification, the more rapid and extensive was the derivatization of free amino groups. Approximately 50-75% of free lysine groups in LDL were modified after incubation with glyceraldehyde, glycolaldehyde, or erythrose for 24-48 h. Less extensive reductions in free amino groups were observed when LDL was incubated with arabinose or glucose, even at high concentration for up to 5 days. LDL modified with glycolaldehyde and glyceraldehyde labeled with (125)I was degraded more extensively by human monocyte-derived macrophages than was (125)I-labeled native LDL. Conversely, LDL modified with (125)I-labeled erythrose, arabinose, or glucose was degraded less rapidly than (125)I-labeled native LDL. Competition for the degradation of LDL modified with (125)I-labeled glyceraldehyde was nearly complete with acetyl-, glycolaldehyde-, and glyceraldehyde-modified LDL, fucoidin, and advanced glycation end product-modified bovine serum albumin, and absent with unlabeled native LDL. These results suggest that short-chain alpha-hydroxy aldehydes react with amino groups on LDL to yield moieties that are important determinants of recognition by macrophage scavenger receptors.

  15. Electronegative Low-density Lipoprotein Increases Coronary Artery Disease Risk in Uremia Patients on Maintenance Hemodialysis

    PubMed Central

    Chang, Chiz-Tzung; Wang, Guei-Jane; Kuo, Chin-Chi; Hsieh, Ju-Yi; Lee, An-Sean; Chang, Chia-Ming; Wang, Chun-Cheng; Shen, Ming-Yi; Huang, Chiu-Ching; Sawamura, Tatsuya; Yang, Chao-Yuh; Stancel, Nicole; Chen, Chu-Huang

    2016-01-01

    Abstract Electronegative low-density lipoprotein (LDL) is a recognized factor in the pathogenesis of coronary artery disease (CAD) in the general population, but its role in the development of CAD in uremia patients is unknown. L5 is the most electronegative subfraction of LDL isolated from human plasma. In this study, we examined the distribution of L5 (L5%) and its association with CAD risk in uremia patients. The LDL of 39 uremia patients on maintenance hemodialysis and 21 healthy controls was separated into 5 subfractions, L1–L5, with increasing electronegativity. We compared the distribution and composition of plasma L5 between uremia patients and controls, examined the association between plasma L5% and CAD risk in uremia patients, and studied the effects of L5 from uremia patients on endothelial function. Compared to controls, uremia patients had significantly increased L5% (P < 0.001) and L5 that was rich in apolipoprotein C3 and triglycerides. L5% was significantly higher in uremia patients with CAD (n = 10) than in those without CAD (n = 29) (P < 0.05). Independent of other major CAD risk factors, the adjusted odds ratio for CAD was 1.88 per percent increase in plasma L5% (95% CI, 1.01–3.53), with a near-linear dose–response relationship. Compared with controls, uremia patients had decreased flow-mediated vascular dilatation. In ex vivo studies with preconstricted rat thoracic aortic rings, L5 from uremia patients inhibited acetylcholine-induced relaxation. In cultured human endothelial cells, L5 inhibited endothelial nitric oxide synthase activation and induced endothelial dysfunction. Our findings suggest that elevated plasma L5% may induce endothelial dysfunction and play an important role in the increased risk of CAD in uremia patients. PMID:26765403

  16. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    PubMed Central

    Funamoto, Masafumi; Sunagawa, Yoichi; Katanasaka, Yasufumi; Miyazaki, Yusuke; Imaizumi, Atsushi; Kakeya, Hideaki; Yamakage, Hajime; Satoh-Asahara, Noriko; Komiyama, Maki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2016-01-01

    Purpose COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD. Patients and methods This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated. Results There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin® group compared with the placebo group. Conclusion Theracurmin® reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects.

  17. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    PubMed Central

    Funamoto, Masafumi; Sunagawa, Yoichi; Katanasaka, Yasufumi; Miyazaki, Yusuke; Imaizumi, Atsushi; Kakeya, Hideaki; Yamakage, Hajime; Satoh-Asahara, Noriko; Komiyama, Maki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2016-01-01

    Purpose COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD. Patients and methods This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated. Results There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin® group compared with the placebo group. Conclusion Theracurmin® reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects. PMID:27616885

  18. Carbohydrate composition of circulating multiple-modified low-density lipoprotein

    PubMed Central

    Zakiev, Emile R; Sobenin, Igor A; Sukhorukov, Vasily N; Myasoedova, Veronika A; Ivanova, Ekaterina A; Orekhov, Alexander N

    2016-01-01

    Atherogenic modification of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis, as modified LDL, but not native LDL, induces pronounced accumulation of cholesterol and lipids in the arterial wall. It is likely that LDL particles undergo multiple modifications in human plasma: desialylation, changes in size and density, acquisition of negative electric charge, oxidation, and complex formation. In a total LDL preparation isolated from pooled plasma of patients with coronary atherosclerosis and from healthy subjects, two subfractions of LDL could be identified: desialylated LDL bound by a lectin affinity column and normally sialylated (native) LDL that passed through the column. The desialylated LDL subfraction therefore represents circulating modified LDL. In this work, we performed a careful analysis of LDL particles to reveal changes in the composition of glycoconjugates associated with proteins and lipids. Protein fraction of LDL from atherosclerotic patients contained similar amounts of glucosamine, galactose, and mannose, but a 1.6-fold lower level of sialic acid as compared to healthy donors. Lipid-bound glycoconjugates of total LDL from patients with coronary atherosclerosis contained 1.5–2-fold less neutral monosaccharides than total LDL from healthy donors. Patient-derived LDL also contained significantly less sialic acid. Our results demonstrate that carbohydrate composition of LDL from atherosclerotic patients was altered in comparison to healthy controls. In particular, prominent decrease in the sialic acid content was observed. This strengthens the hypothesis of multiple modification of LDL particles in the bloodstream and underscores the clinical importance of desialylated LDL as a possible marker of atherosclerosis progression. PMID:27789955

  19. Preliminary Analysis of Modified Low-Density Lipoproteins in the Serum of Healthy and Obese Dogs and Cats

    PubMed Central

    Mori, Nobuko; Okada, Yuki; Tsuchida, Naoto; Hatano, Yutaka; Habara, Makoto; Ishikawa, Shingo; Yamamoto, Ichiro; Arai, Toshiro

    2015-01-01

    Oxidized low-density lipoprotein (LDL) is thought to play an important role in the inflammatory response associated with human obesity. The purpose of this preliminary study was to determine oxidized LDL concentrations in healthy dogs and cats, and to evaluate whether obesity affects oxidized LDL concentration, using 39 cats and 19 dogs that had visited two different veterinary clinics in Japan. We hypothesized that oxidized LDL concentrations measured against body condition score (BCS) may have a potential value in evaluating the qualities of accumulated or circulating lipids in obese dogs and cats that do not show signs of metabolic diseases. The mean oxidized LDL value in BCS3 dogs (2.4 ± 0.9 μg/dl) was very similar to that of BCS5 dogs (2.2 ± 0.3 μg/dl). The mean oxidized LDL value of BCS4 dogs was 7.2 ± 10.3 μg/dl and the highest among three groups. BCS4 dogs included two dogs whose oxidized LDL values were higher than the mean oxidized LDL value of healthy humans (11.2 ± 0.3 μg/dl). On the other hand, the mean oxidized LDL value of BCS3 cats was 2.5 ± 0.9 μg/dl, and those of BCS4 and 5 cats were higher than that of BCS3, but there was no significant difference. The BCS4 cat group included one cat with a higher oxidized LDL value, and the BCS5 group also included two cats with oxidized LDL values higher than the mean oxidized LDL value of healthy humans. Interestingly, the oxidized LDL values in two obese dogs and three obese cats were indeed higher than the mean oxidized LDL value of humans with coronary artery disease (20.1 ± 1.1 μg/dl). In conclusion, this preliminary study showed reference ranges of oxidized dogs and cats against BCS. Obesity alone does not appear to have any direct effect on serum oxidized LDL values in healthy dogs and cats. PMID:26664963

  20. The non-thermal origin of the tokamak low-density stability limit

    DOE PAGESBeta

    Paz-Soldan, C.; La Haye, R. J.; Shiraki, D.; Buttery, R. J.; Eidietis, N. W.; Hollmann, E. M.; Moyer, R. A.; Boom, J. E.; Chapman, I. T.

    2016-04-13

    DIII-D plasmas at very low density exhibit onset of n=1 error field (EF) penetration (the `low-density locked mode') not at a critical density or EF, but instead at a critical level of runaway electron (RE) intensity. Raising the density during a discharge does not avoid EF penetration, so long as RE growth proceeds to the critical level. Penetration is preceded by non-thermalization of the electron cyclotron emission, anisotropization of the total pressure, synchrotron emission shape changes, as well as decreases in the loop voltage and bulk thermal electron temperature. The same phenomena occur despite various types of optimal EF correction,more » and in some cases modes are born rotating. Similar phenomena are also found at the low-density limit in JET. These results stand in contrast to the conventional interpretation of the low-density stability limit as being due to residual EFs and demonstrate a new pathway to EF penetration instability due to REs. Existing scaling laws for penetration project to increasing EF sensitivity as bulk temperatures decrease, though other possible mechanisms include classical tearing instability, thermo-resistive instability, and pressure-anisotropy driven instability. Regardless of first-principles mechanism, known scaling laws for Ohmic energy confinement combined with theoretical RE production rates allow rough extrapolation of the RE criticality condition, and thus, the low-density limit to other tokamaks. Furthermore, the extrapolated low-density limit by this pathway decreases with increasing machine size and is considerably below expected operating conditions for ITER. While likely unimportant for ITER, this effect can explain the low-density limit of existing tokamaks operating with small residual EFs.« less

  1. Metabolism of a Lipid Nanoemulsion Resembling Low-Density Lipoprotein in Patients with Grade III Obesity

    PubMed Central

    Dantas, Simone Alves; Ficker, Elisabeth Salvatori; Vinagre, Carmen G. C.; Ianni, Barbara Maria; Maranhão, Raul Cavalcante; Mady, Charles

    2010-01-01

    INTRODUCTION: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. OBJECTIVE: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. METHODS: A low-density emulsion was labeled with [14C]-cholesterol ester and [3H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m2] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. RESULTS: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h−1) was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971) in the controls. CONCLUSION: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower. PMID:20126342

  2. The non-thermal origin of the tokamak low-density stability limit

    NASA Astrophysics Data System (ADS)

    Paz-Soldan, C.; La Haye, R. J.; Shiraki, D.; Buttery, R. J.; Eidietis, N. W.; Hollmann, E. M.; Moyer, R. A.; Boom, J. E.; Chapman, I. T.; Contributors, JET

    2016-05-01

    DIII-D plasmas at very low density exhibit the onset of n  =  1 error field (EF) penetration (the ‘low-density locked mode’) not at a critical density or EF, but instead at a critical level of runaway electron (RE) intensity. Raising the density during a discharge does not avoid EF penetration, so long as RE growth proceeds to the critical level. Penetration is preceded by non-thermalization of the electron cyclotron emission, anisotropization of the total pressure, synchrotron emission shape changes, as well as decreases in the loop voltage and bulk thermal electron temperature. The same phenomena occur despite various types of optimal EF correction, and in some cases modes are born rotating. Similar phenomena are also found at the low-density limit in JET. These results stand in contrast to the conventional interpretation of the low-density stability limit as being due to residual EFs and demonstrate a new pathway to EF penetration instability due to REs. Existing scaling laws for penetration project to increasing EF sensitivity as bulk temperatures decrease, though other possible mechanisms include classical tearing instability, thermo-resistive instability, and pressure-anisotropy driven instability. Regardless of the first-principles mechanism, known scaling laws for Ohmic energy confinement combined with theoretical RE production rates allow rough extrapolation of the RE criticality condition, and thus the low-density limit, to other tokamaks. The extrapolated low-density limit by this pathway decreases with increasing machine size and is considerably below expected operating conditions for ITER. While likely unimportant for ITER, this effect can explain the low-density limit of existing tokamaks operating with small residual EFs.

  3. The effects of weight gain after smoking cessation on atherogenic α1-antitrypsin-low-density lipoprotein.

    PubMed

    Komiyama, Maki; Wada, Hiromichi; Ura, Shuichi; Yamakage, Hajime; Satoh-Asahara, Noriko; Shimada, Sayaka; Akao, Masaharu; Koyama, Hiroshi; Kono, Koichi; Shimatsu, Akira; Takahashi, Yuko; Hasegawa, Koji

    2015-11-01

    Although cardiovascular risks decrease after quitting smoking, body weight often increases in the early period after smoking cessation. We have previously reported that the serum level of the α1-antitrypsin-low-density lipoprotein complex (AT-LDL)-an oxidatively modified low-density lipoprotein that accelerates atherosclerosis-is high in current smokers, and that the level rapidly decreases after smoking cessation. However, the effects of weight gain after smoking cessation on this cardiovascular marker are unknown. In 183 outpatients (134 males, 49 females) who had successfully quit smoking, serum AT-LDL levels were measured using an enzyme-linked immunosorbent assay. For all persons who had successfully quit smoking, body mass index (BMI) significantly increased 12 weeks after the first examination (p < 0.01). Among patients with a BMI increase smaller than the median, a significant decrease (p < 0.01) in serum AT-LDL values was found, but no significant changes in serum AT-LDL values were found in patients with a BMI increase greater than the median. The findings suggest that the decrease in serum AT-LDL levels after quitting smoking is influenced by weight gain after smoking cessation.

  4. Low-Density Lipoprotein Receptor-Related Protein-1 Protects Against Hepatic Insulin Resistance and Hepatic Steatosis.

    PubMed

    Ding, Yinyuan; Xian, Xunde; Holland, William L; Tsai, Shirling; Herz, Joachim

    2016-05-01

    Low-density lipoprotein receptor-related protein-1 (LRP1) is a multifunctional uptake receptor for chylomicron remnants in the liver. In vascular smooth muscle cells LRP1 controls reverse cholesterol transport through platelet-derived growth factor receptor β (PDGFR-β) trafficking and tyrosine kinase activity. Here we show that LRP1 regulates hepatic energy homeostasis by integrating insulin signaling with lipid uptake and secretion. Somatic inactivation of LRP1 in the liver (hLRP1KO) predisposes to diet-induced insulin resistance with dyslipidemia and non-alcoholic hepatic steatosis. On a high-fat diet, hLRP1KO mice develop a severe Metabolic Syndrome secondary to hepatic insulin resistance, reduced expression of insulin receptors on the hepatocyte surface and decreased glucose transporter 2 (GLUT2) translocation. While LRP1 is also required for efficient cell surface insulin receptor expression in the absence of exogenous lipids, this latent state of insulin resistance is unmasked by exposure to fatty acids. This further impairs insulin receptor trafficking and results in increased hepatic lipogenesis, impaired fatty acid oxidation and reduced very low density lipoprotein (VLDL) triglyceride secretion. PMID:27322467

  5. Influence of Pro-Oxidant on Photodegradation of a Low-Density Polyethylene-Nanosilica Composite

    EPA Science Inventory

    Use of polymer nanocomposites is burgeoning and they represent one of the fastest growing components of the manufactured nanomaterials market. Incorporation of nanoscale fillers in these plastics significantly improves their stiffness and other key mechanical properties. Although...

  6. Variations in transmembrane Ca2+ gradient and apoptosis of macrophages induced by oxidized low density lipoprotein.

    PubMed

    Yang, X; Zhang, Y; Huang, Y; Yang, F

    2001-10-01

    While Ca2+ has been proposed to be a messenger in OxLDL-induced cell death, few studies have addressed the possibility that it may influence the occurrence of apoptosis and necrosis of macrophages induced by OxLDL in virtue of change of transmembrane Ca2+ gradient including that across plasma membrane and intracellular organelle membranes. In this paper, various lipophilic Ca2+ fluorescent indicators and specific organelle markers were used to study the relationship between the changes of the transmembrane Ca2+ gradients and the OxLDL induced apoptosis of macrophages. Our results showed that following exposure of low dose OxLDL to macrophages, the transmembrane Ca2+ gradient across the plasma membrane, as well as the membrane-proximal Ca2+ gradient, the transnuclear, and the transmitochondrial membrane Ca2+ gradient were all changed significantly. These data suggested that changes in transmembrane Ca2+ gradients might be involved in the apoptosis of macrophages induced by OxLDL.

  7. Enhanced oxidation of air contaminants on an ultra-low density UV-accessible aerogel photocatalyst

    SciTech Connect

    Dreyer, M.; Newman, G.K.; Lobban, L.; Kersey, S.J.; Wang, R.; Harwell, J.H.

    1997-12-31

    This research developed new forms of photocatalysts that could potentially move photocatalytic degradation of air contaminants into the main stream of industrially used remediation technologies. Tests of the photocatalytic activity of the TiO{sub 2} aerogel catalysts have been carried out using both acetone and methane as the air contaminant. For comparison, the same tests were carried out on a standard (non-aerogel) anatase powder. Despite having very low crystallinity, the aerogel decontaminates the air far more effectively than an equal volume of the anatase powder which indicates that a much larger fraction of the aerogel is activated by the UV light. Experimental data were used to determine adsorption equilibrium constants for acetone, and to determine reaction rate constants assuming a Langmuir-Hinshelwood type rate expression.

  8. Viscous linear stability of axisymmetric low-density jets: Parameters influencing absolute instability

    NASA Astrophysics Data System (ADS)

    Srinivasan, V.; Hallberg, M. P.; Strykowski, P. J.

    2010-02-01

    Viscous linear stability calculations are presented for model low-density axisymmetric jet flows. Absolute growth transitions for the jet column mode are mapped out in a parametric space including velocity ratio, density ratio, Reynolds number, momentum thickness, and subtle differences between velocity and density profiles. Strictly speaking, the profiles used in most jet stability studies to date are only applicable to unity Prandtl numbers and zero pressure gradient flows—the present work relaxes this requirement. Results reveal how subtle differences between the velocity and density profiles generally used in jet stability theory can dramatically alter the absolute growth rate of the jet column mode in these low-density flows. The results suggest heating/cooling or mass diffusion at the outer nozzle surface can suppress absolute instability and potentially global instability in low-density jets.

  9. A Simplified Method for Ultra-Low Density, Long-Term Primary Hippocampal Neuron Culture.

    PubMed

    Lu, Zhongming; Piechowicz, Mariel; Qiu, Shenfeng

    2016-01-01

    Culturing primary hippocampal neurons in vitro facilitates mechanistic interrogation of many aspects of neuronal development. Dissociated embryonic hippocampal neurons can often grow successfully on glass coverslips at high density under serum-free conditions, but low density cultures typically require a supply of trophic factors by co-culturing them with a glia feeder layer, preparation of which can be time-consuming and laborious. In addition, the presence of glia may confound interpretation of results and preclude studies on neuron-specific mechanisms. Here, a simplified method is presented for ultra-low density (~2,000 neurons/cm2), long-term (>3 months) primary hippocampal neuron culture that is under serum free conditions and without glia cell support. Low density neurons are grown on poly-D-lysine coated coverslips, and flipped on high density neurons grown in a 24-well plate. Instead of using paraffin dots to create a space between the two neuronal layers, the experimenters can simply etch the plastic bottom of the well, on which the high density neurons reside, to create a microspace conducive to low density neuron growth. The co-culture can be easily maintained for >3 months without significant loss of low density neurons, thus facilitating the morphological and physiological study of these neurons. To illustrate this successful culture condition, data are provided to show profuse synapse formation in low density cells after prolonged culture. This co-culture system also facilitates the survival of sparse individual neurons grown in islands of poly-D-lysine substrates and thus the formation of autaptic connections. PMID:27022758

  10. Experimental demonstration of laser to x-ray conversion enhancements with low density gold targets

    DOE PAGESBeta

    Shang, Wanli; Yang, Jiamin; Zhang, Wenhai; Li, Zhichao; Deng, Bo; Dong, Yunsong; Zhu, Tuo; Huang, Chengwu; Zhan, Xiayu; Mei, Yu; et al

    2016-02-12

    The enhancement of laser to x-ray conversion efficiencies using low density gold targets [W. L. Shang, J. M. Yang, and Y. S. Dong, Appl. Phys. Lett. 102, 094105 (2013)] is demonstrated. Laser to x-ray conversion efficiencies with 6.3% and 12% increases are achieved with target densities of 1 and 0.25 g/cm3, when compared with that of a solid gold target (19.3 g/cm3). Experimental data and numerical simulations are in good agreement. Lastly, the enhancement is caused by larger x-ray emission zone lengths formed in low density targets, which is in agreement with the simulation results.

  11. Proteome of human plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism.

    PubMed

    Dashty, M; Motazacker, M M; Levels, J; de Vries, M; Mahmoudi, M; Peppelenbosch, M P; Rezaee, F

    2014-03-01

    Apart from transporting lipids through the body, the human plasma lipoproteins very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) are also thought to serve as a modality for intra-organismal protein transfer, shipping proteins with important roles in inflammation and thrombosis from the site of synthesis to effector locations. To better understand the role of VLDL and LDL in the transport of proteins, we applied a combination of LTQ ORBITRAP-XL (nLC-MS/MS) with both in-SDS-PAGE gel and in-solution tryptic digestion of pure and defined VLDL and LDL fractions. We identified the presence of 95 VLDL- and 51 LDL-associated proteins including all known apolipoproteins and lipid transport proteins, and intriguingly a set of coagulation proteins, complement system and anti- microbial proteins. Prothrombin, protein S, fibrinogen γ, PLTP, CETP, CD14 and LBP were present on VLDL but not on LDL. Prenylcysteine oxidase 1, dermcidin, cathelicidin antimicrobial peptide, TFPI-1 and fibrinogen α chain were associated with both VLDL and LDL. Apo A-V is only present on VLDL and not on LDL. Collectively, this study provides a wealth of knowledge on the protein constituents of the human plasma lipoprotein system and strongly supports the notion that protein shuttling through this system is involved in the regulation of biological processes. Human diseases related to proteins carried by VLDL and LDL can be divided in three major categories: 1 - dyslipidaemia, 2 - atherosclerosis and vascular disease, and 3 - coagulation disorders. PMID:24500811

  12. Highly Shocked Low Density Sedimentary Rocks from the Haughton Impact Structure, Devon Island, Nunavut, Canada

    NASA Technical Reports Server (NTRS)

    Osinski, G. R.; Spray, J. G.

    2001-01-01

    We present the preliminary results of a detailed investigation of the shock effects in highly shocked, low density sedimentary rocks from the Haughton impact structure. We suggest that some textural features can be explained by carbonate-silicate immiscibility. Additional information is contained in the original extended abstract.

  13. Growth requirements of low-density rabbit costal chondrocyte cultures maintained in serum-free medium.

    PubMed

    Kato, Y; Gospodarowicz, D

    1984-09-01

    The factors required for the active proliferation of low-density rabbit costal chondrocytes exposed to 9:1 (v/v) mixture of Dulbecco's modified Eagle's medium and Ham's F12 medium have been defined. Low-density primary cultures of rabbit costal chondrocytes proliferated actively when the medium was supplemented with high-density lipoprotein (300 micrograms/ml), transferrin (60 micrograms/ml), fibroblast growth factor (FGF) (1 ng/ml), hydrocortisone (10(-6) M), and epidermal growth factor (EGF) (30 ng/ml). Insulin, although it slightly decreased the final cell density, was required for reexpression of the cartilage phenotype at confluence. Optimal proliferation of low-density chondrocyte cultures was only observed when dishes were coated with an extracellular matrix (ECM) produced by cultured corneal endothelial cells, but not on plastic. Furthermore, serum-free chondrocyte cultures seeded at low density and maintained on ECM-coated dishes gave rise to a homogeneous cartilage-like tissue composed of spherical cells. These chondrocytes therefore seem to provide a good experimental system for analyzing factors involved in supporting proliferation of chondrocytes and their phenotypic expression.

  14. Glycated albumin and direct low density lipoprotein cholesterol levels in type 2 diabetes mellitus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

  15. Low density lipoprotein receptor related protein 1 variant interacts with saturated fatty acids in Puerto Ricans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low density lipoprotein related receptor protein 1 (LRP1) is a multi-functional endocytic receptor that is highly expressed in adipocytes and the hypothalamus. Animal models and in vitro studies support a role for LRP1 in adipocyte metabolism and leptin signaling, but genetic polymorphisms have not ...

  16. Securing the Extremely Low-Densities of Low-Mass Planets Characterized by Transit Timing Variations

    NASA Astrophysics Data System (ADS)

    Ford, Eric B.

    2015-12-01

    Transit timing variations (TTVs) provide an excellent tool to characterize the masses and orbits of dozens of small planets, including many at orbital periods beyond the reach of both Doppler surveys and photoevaporation-induced atmospheric loss. Dynamical modeling of these systems has identified low-mass planets with surprisingly large radii and low densities (e.g., Kepler-79d, Jontof-Hutter et al. 2014; Kepler-51, Masuda 2014; Kepler-87c, Ofir et al. 2014). Additional low-density, low-mass planets will likely become public before ESS III (Jontof-Hutter et al. in prep). Collectively, these results suggest that very low density planets with masses of 2-6 MEarth are not uncommon in compact multiple planet systems. Some astronomers have questioned whether there could be an alternative interpretation of the TTV observations. Indeed, extraordinary claims require extraordinary evidence. While the physics of TTVs is rock solid, the statistical analysis of Kepler observations can be challenging, due to the complex interactions between model parameters and high-dimensional parameter spaces that must be explored. We summarize recent advances in computational statistics that enable robust characterization of planetary systems using TTVs. We present updated analyses of a few particularly interesting systems and discuss the implications for the robustness of extremely low densities for low-mass planets. Such planets pose an interesting challenge for planet formation theory and are motivating detailed theoretical studies (e.g., Lee & Chiang 2015 and associated ESS III abstracts).

  17. Optimal design of low-density SNP arrays for genomic prediction: algorithm and applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low-density (LD) single nucleotide polymorphism (SNP) arrays provide a cost-effective solution for genomic prediction and selection, but algorithms and computational tools are needed for their optimal design. A multiple-objective, local optimization (MOLO) algorithm was developed for design of optim...

  18. Low density biodegradable shape memory polyurethane foams for embolic biomedical applications

    PubMed Central

    Singhal, Pooja; Small, Ward; Cosgriff-Hernandez, Elizabeth; Maitland, Duncan J; Wilson, Thomas S

    2014-01-01

    Low density shape memory polymer foams hold significant interest in the biomaterials community for their potential use in minimally invasive embolic biomedical applications. The unique shape memory behavior of these foams allows them to be compressed to a miniaturized form, which can be delivered to an anatomical site via a transcatheter process, and thereafter actuated to embolize the desired area. Previous work in this field has described the use of a highly covalently crosslinked polymer structure for maintaining excellent mechanical and shape memory properties at the application-specific ultra low densities. This work is aimed at further expanding the utility of these biomaterials, as implantable low density shape memory polymer foams, by introducing controlled biodegradability. A highly covalently crosslinked network structure was maintained by use of low molecular weight, symmetrical and polyfunctional hydroxyl monomers such as Polycaprolactone triol (PCL-t, Mn 900 g), N,N,N0,N0-Tetrakis (hydroxypropyl) ethylenediamine (HPED), and Tris (2-hydroxyethyl) amine (TEA). Control over the degradation rate of the materials was achieved by changing the concentration of the degradable PCL-t monomer, and by varying the material hydrophobicity. These porous SMP materials exhibit a uniform cell morphology and excellent shape recovery, along with controllable actuation temperature and degradation rate. We believe that they form a new class of low density biodegradable SMP scaffolds that can potentially be used as “smart” non-permanent implants in multiple minimally invasive biomedical applications. PMID:24090987

  19. Use of Low-Density DNA Microarrays and Photopolymerization for Genotyping Foodborne-Associated Noroviruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human noroviruses cause up to 21 million cases of foodborne disease in the United States annually and are the most common cause of acute gastroenteritis in industrialized countries. To reduce the burden of foodborne disease associated with viruses, the use of low density DNA microarrays in conjunct...

  20. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Low-density lipoprotein immunological test system. 866.5600 Section 866.5600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  1. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Low-density lipoprotein immunological test system. 866.5600 Section 866.5600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  2. Direct Low Density Lipoprotein Cholesterol and Glycated Albumin Levels in Type 2 Diabetes Mellitus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) have been associated with a decreased risk of these complications. The aim in this st...

  3. Distinct Hepatic Receptors for Low Density Lipoprotein and Apolipoprotein E in Humans

    NASA Astrophysics Data System (ADS)

    Hoeg, Jeffrey M.; Demosky, Stephen J.; Gregg, Richard E.; Schaefer, Ernst J.; Brewer, H. Bryan

    1985-02-01

    Since the liver is a central organ for lipid and lipoprotein synthesis and catabolism, hepatic receptors for specific apolipoproteins on plasma lipoproteins would be expected to modulate lipid and lipoprotein metabolism. The role of hepatic receptors for low density lipoproteins and apolipoprotein E-containing lipoproteins was evaluated in patients with complementary disorders in lipoprotein metabolism: abetalipoproteinemia and homozygous familial hypercholesterolemia. In addition, hepatic membranes from a patient with familial hypercholesterolemia were studied and compared before and after portacaval shunt surgery. The results establish that the human liver has receptors for apolipoproteins B and E. Furthermore, in the human, hepatic receptors for low density lipoproteins and apolipoprotein E are genetically distinct and can undergo independent control.

  4. Low-density lipoprotein subclass patterns and risk of myocardial infarction.

    PubMed

    Austin, M A; Breslow, J L; Hennekens, C H; Buring, J E; Willett, W C; Krauss, R M

    1988-10-01

    The association of low-density lipoprotein (LDL) subclass patterns with coronary heart disease was investigated in a case-control study of nonfatal myocardial infarction. Subclasses of LDL were analyzed by gradient gel electrophoresis of plasma samples from 109 cases and 121 controls. The LDL subclass pattern characterized by a preponderance of small, dense LDL particles was significantly associated with a threefold increased risk of myocardial infarction, independent of age, sex, and relative weight. Plasma levels of high-density lipoprotein cholesterol were decreased, and levels of triglyceride, very low-density lipoproteins, and intermediate-density lipoproteins were increased in subjects with this LDL subclass pattern. Multivariate logistic regression analyses showed that both high-density lipoprotein cholesterol and triglyceride levels contributed to the risk associated with the small, dense LDL subclass pattern. Thus, the metabolic trait responsible for this LDL subclass pattern results in a set of interrelated lipoprotein changes that lead to increased risk of coronary heart disease.

  5. Security of a Class of Knapsack Public-Key Cryptosystems against Low-Density Attack

    NASA Astrophysics Data System (ADS)

    Nasako, Takeshi; Murakami, Yasuyuki; Kasahara, Masao

    In 2003, Kobayashi et al. proposed a new class of knapsack public-key cryptosystems over Gaussian integer ring. This scheme using two-sequences as the public key. In 2005, Sakamoto and Hayashi proposed an improved version of Kobayashi's scheme. In this paper, we propose the knapsack PKC using l-sequences as the public key and present the low-density attack on it. We have described Schemes R and G for l=2, in which the public keys are constructed over rational integer ring and over Gaussian integer ring, respectively. We discusses on the difference of the security against the low-density attack. We show that the security levels of Schemes R and G differ only slightly.

  6. A modified thermal conductivity for low density plasma magnetic flux tubes

    NASA Technical Reports Server (NTRS)

    Comfort, R. H.; Craven, P. D.; Richards, P. G.

    1995-01-01

    In response to inconsistencies which have arisen in results from a hydrodynamic model in simulation of high ion temperature (1-2 eV) observed in low density, outer plasmasphere flux tubes, we postulate a reduced thermal conductivity coefficient in which only particles in the loss cone of the quasi-collisionless plasma contribute to the thermal conduction. Other particles are assumed to magnetically mirror before they reach the topside ionosphere and therefore not to remove thermal energy from the plasmasphere. This concept is used to formulate a mathematically simple, but physically limiting model for a modified thermal conductivity coefficient. When this modified coefficient is employed in the hydrodynamic model in a case study, the inconsistencies between simulation results and observations are largely resolved. The high simulated ion temperatures are achieved with significantly lower ion temperatures in the topside ionosphere. We suggest that this mechanism may be operative under the limited low density, refilling conditions in which high ion temperatures are observed.

  7. Thermodynamics of the low-density excluded-volume hadron gas

    NASA Astrophysics Data System (ADS)

    Redlich, Krzysztof; Zalewski, Kacper

    2016-01-01

    We consider the thermodynamics of excluded-volume particles at finite temperature and chemical potential in the low-density approximation. We assume Boltzmann statistics and study the influence of the excluded volume on an ideal gas thermodynamics at the same temperature, pressure, and number of particles. We show that considering the change of the free enthalpy due to the excluded volume, and using the Maxwell identities, one can derive relevant thermodynamic functions and parameters of multicomponent gases. The derivation is quite general, because particles may have different sizes and shapes which can also depend on their momenta. Besides its simplicity and generality, our approach has the advantage of eliminating the transcendental equations occurring in earlier studies. A representative example of the excluded-volume thermodynamics is the single-component gas of hard spheres. For this case, using a virial expansion, the validity limits of the low-density approximation are also discussed.

  8. The Fabrication of Low Density, Small Cell Polystyrene Foam Parts with High Quality Surface Finish

    NASA Astrophysics Data System (ADS)

    Duke, J. R.; Gobby, P. L.; Hollis, R. V.; Manzanares, R.; Moore, J. E.; Gomez, V. M.; Elliott, N. E.; Foreman, L. R.

    1997-11-01

    Foams are frequently used in Inertial Confinement Fusion and other high energy density physics experiments when low density starting materials are desired in targets. Small cell size, low density, structural integrity and fabricability are most often the desired properties of the foam materials. We report in this paper a technique we have used to produce rigid polystyrene foam parts with cell sizes of 2-3 microns, densities down to 30 mg/cc and machined surfaces of 2-3 microns, rms. This feat is accomplished by backfilling a larger foam piece with a low melting point surfactant or wax, machining the desired parts from the backfilled part, and subsequently leaching the surfactant (or wax) from the finished part. An average 2 percent shrinkage is observed when the parts are leached, but the parts show no resulting distortion. Density checks of the finished parts indicate the surfactant (wax) is essentially entirely removed by the leaching process.

  9. Shock initiation experiments with ignition and growth modeling on low density HMX

    NASA Astrophysics Data System (ADS)

    Garcia, Frank; Vandersall, Kevin S.; Tarver, Craig M.

    2014-05-01

    Shock initiation experiments on low density (~1.2 and ~1.6 g/cm3) HMX were performed to obtain in-situ pressure gauge data, characterize the run-distance-to-detonation behavior, and provide a basis for Ignition and Growth reactive flow modeling. A 101 mm diameter gas gun was utilized to initiate the explosive charges with manganin piezoresistive pressure gauge packages placed between packed layers (~1.2 g/cm3) or sample disks pressed to low density (~1.6 g/cm3). The measured shock sensitivity of the ~1.2 g/cm3 HMX was similar to that previously measured by Sheffield et al. and the ~1.6 g/cm3 HMX was measured to be much less shock sensitive. Ignition and Growth model parameters were utilized that yielded good agreement with the experimental data at both initial densities.

  10. Low density, microcellular, dopable, agar/gelatin foams for pulsed power experiments

    SciTech Connect

    McNamara, W.F.; Aubert, J.H.

    1997-04-01

    Low-density, microcellular foams prepared from the natural polymers agar and gelatin have been developed for pulsed-power physics experiments. Numerous experiments were supported with foams having densities at or below 10 mg/cm{sup 3}. For some of the experiments, the agar/gelatin foam was uniformly doped with metallic elements using soluble salts. Depending on the method of preparation, cell sizes were typically below 10 microns and for one process were below 1.0 micron.

  11. Inertial Alfven-Wave-Driven Convective Cells in Low-Density Plasmas

    SciTech Connect

    Pokhotelov, O.A.; Onishchenko, O.G.; Sagdeev, R.Z.; Stenflo, L.; Balikhin, M.A.

    2005-10-15

    The parametric interaction of inertial Alfven waves with large-scale convective cells in a low-density plasma is investigated. It is shown that, in plasmas where the Alfven velocity is comparable to or exceeds the speed of light, the parametric interaction is substantially suppressed. A compact expression for the optimal scale and instability growth rate of the fastest growing mode is obtained. The relevance of our theory to spacecraft measurements in the Earth's ionosphere is discussed.

  12. Low density lipoprotein uptake by an endothelial-smooth muscle cell bilayer

    SciTech Connect

    Alexander, J.J.; Miguel, R.; Graham, D. )

    1991-03-01

    To study the interaction of endothelial and smooth muscle cells, and the means by which such interaction may affect lipid permeability of the arterial wall, cell bilayers were established by use of a transwell culture system. After confluent growth of both cell types had been achieved, iodine 125 bound to low-density lipoprotein (10 ng protein/ml) was added to the media of the upper well. After a 3-hour incubation period, the iodine 125-bound low-density lipoprotein content of the upper and lower media demonstrated an impedance to lipoprotein movement across the endothelial cell monolayer as compared to the bare porous polycarbonate filter of the transwell (p less than 10(-6)). The presence of smooth muscle cells in the bottom well significantly enhanced the permeability of the endothelial cell layer (p less than 10(-60)). This effect remained unchanged over a 9-day time course. Membrane binding and cellular uptake of low-density lipoprotein by endothelial cells was not altered by smooth muscle cells, indicating that this change in permeability could not be easily attributed to changes in receptor-mediated transport or transcytosis. Membrane binding (p less than 0.02) and cellular uptake (p less than 10(-6)) of low-density lipoprotein by smooth muscle cells in the bilayer, when adjusted for counts available in the smooth muscle cell media, were both reduced in the early incubation period as compared to isolated smooth muscle cells. The disproportionate reduction in uptake as compared to binding would suggest that this was not entirely a receptor-dependent process.

  13. The Low Density Matter (LDM) beamline at FERMI: optical layout and first commissioning

    PubMed Central

    Svetina, Cristian; Grazioli, Cesare; Mahne, Nicola; Raimondi, Lorenzo; Fava, Claudio; Zangrando, Marco; Gerusina, Simone; Alagia, Michele; Avaldi, Lorenzo; Cautero, Giuseppe; de Simone, Monica; Devetta, Michele; Di Fraia, Michele; Drabbels, Marcel; Feyer, Vitaliy; Finetti, Paola; Katzy, Raphael; Kivimäki, Antti; Lyamayev, Viktor; Mazza, Tommaso; Moise, Angelica; Möller, Thomas; O’Keeffe, Patrick; Ovcharenko, Yevheniy; Piseri, Paolo; Plekan, Oksana; Prince, Kevin C.; Sergo, Rudi; Stienkemeier, Frank; Stranges, Stefano; Coreno, Marcello; Callegari, Carlo

    2015-01-01

    The Low Density Matter (LDM) beamline has been built as part of the FERMI free-electron laser (FEL) facility to serve the atomic, molecular and cluster physics community. After the commissioning phase, it received the first external users at the end of 2012. The design and characterization of the LDM photon transport system is described, detailing the optical components of the beamline. PMID:25931066

  14. Interaction of laser radiation with a low-density structured absorber

    NASA Astrophysics Data System (ADS)

    Rozanov, V. B.; Barishpol'tsev, D. V.; Vergunova, G. A.; Demchenko, N. N.; Ivanov, E. M.; Aristova, E. N.; Zmitrenko, N. V.; Limpouch, I.; Ulschmidt, I.

    2016-02-01

    A theoretical model is proposed for computing simulations of laser radiation interaction with inhomogeneous foam materials doped with heavy elements and undoped materials. The model satisfactorily describes many experiments on the interaction of the first and third harmonics of a 200 J pulsed PALS iodine laser with low-density porous cellulose triacetate targets. The model can be used to analyze experimental data and estimate the reality of experimental results.

  15. Simulation of Low-density Nozzle Plumes in Non-zero Ambient Pressures

    NASA Technical Reports Server (NTRS)

    Chung, Chan-Hong; Dewitt, Kenneth J.; Stubbs, Robert M.; Penko, Paul F.

    1994-01-01

    The direct simulation Monte-Carlo (DSMC) method was applied to the analysis of low-density nitrogen plumes exhausting from a small converging-diverging nozzle into finite ambient pressures. Two cases were considered that simulated actual test conditions in a vacuum facility. The numerical simulations readily captured the complicated flow structure of the overexpanded plumes adjusting to the finite ambient pressures, including Mach disks and barrel shaped shocks. The numerical simulations compared well to experimental data of Rothe.

  16. Physics of spacecraft-based interplanetary dust collection by impact into low-density media

    NASA Technical Reports Server (NTRS)

    Anderson, William W.; Ahrens, T. J.

    1994-01-01

    A spacecraft encountering an interplanetary dust particle (IDP) at a relative velocity of several kilometers per second may be used to capture that particle for in situ analysis or for analysis upon Earth return. In this paper we study the impact of a dust particle into a low-density medium (i.e., a foam) such that the foam dissipates the kinetic energy of impact over a sufficient distance to stop the particle without destroying it.

  17. Membrane receptors for very low density lipoprotein (VLDL) inhibitor of lymphocyte proliferation

    SciTech Connect

    Yi, P.I.; Beck, G.; Zucker, S.

    1981-06-01

    Physiologic concentrations of human plasma very low density lipoproteins inhibit the DNA synthesis of lymphocytes stimulated by allogeneic cells or lectins. In this report reachers have compared the effects of isolated lipoproteins (very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL)) and lipoprotein-depleted plasma (LDP) on DNA synthesis by phytohemagglutinin-stimulated human lymphocytes. The relative potency for the inhibition of lymphocyte proliferation was VLDL greater than LDL greater than HDL greater than LDP. Fifty percent inhibition of DNA synthesis was observed at a VLDL protein concentration of 1.5--2.0 microgram/ml. Researchers have further demonstrated the presence of specific receptors for VLDL on human lymphocytes. Native VLDL was more effective than LDL in competing for 125I-VLDL binding sites. Subsequent to binding to lymphocytes, 125I-VLDL was internalized and degraded to acid-soluble products. Based on a Scatchard analysis of VLDL binding at 4 degrees C, the number of VLDL receptors per lymphocyte was estimated at 28,000 +/- 1300. Based on an estimated mean binding affinity for the VLDL receptor complex at half saturation of approximately 8.8 X 10(7) liter/mole, it is estimated that 91% of lymphocyte VLDL receptors are occupied at physiologic VLDL concentrations in blood. Although the immune regulatory role of plasma lipoproteins is uncertain, researchers suggest tha VLDL and LDL-In may maintain circulating blood lymphocytes in a nonproliferative state via their respective cell receptor mechanisms.

  18. Galaxy clusters and cold dark matter - A low-density unbiased universe?

    NASA Technical Reports Server (NTRS)

    Bahcall, Neta A.; Cen, Renyue

    1992-01-01

    Large-scale simulations of a universe dominated by cold dark matter (CDM) are tested against two fundamental properties of clusters of galaxies: the cluster mass function and the cluster correlation function. We find that standard biased CDM models are inconsistent with these observations for any bias parameter b. A low-density, low-bias CDM-type model, with or without a cosmological constant, appears to be consistent with both the cluster mass function and the cluster correlations. The low-density model agrees well with the observed correlation function of the Abell, Automatic Plate Measuring Facility (APM), and Edinburgh-Durham cluster catalogs. The model is in excellent agreement with the observed dependence of the correlation strength on cluster mean separation, reproducing the measured universal dimensionless cluster correlation. The low-density model is also consistent with other large-scale structure observations, including the APM angular galaxy-correlations, and for lambda = 1-Omega with the COBE results of the microwave background radiation fluctuations.

  19. Pairs of galaxies in low density regions of a combined redshift catalog

    NASA Technical Reports Server (NTRS)

    Charlton, Jane C.; Salpeter, Edwin E.

    1990-01-01

    The distributions of projected separations and radial velocity differences of pairs of galaxies in the CfA and Southern Sky Redshift Survey (SSRS) redshift catalogs are examined. The authors focus on pairs that fall in low density environments rather than in clusters or large groups. The projected separation distribution is nearly flat, while uncorrelated galaxies would have given one linearly rising with r sub p. There is no break in this curve even below 50 kpc, the minimum halo size consistent with measured galaxy rotation curves. The significant number of pairs at small separations is inconsistent with the N-body result that galaxies with overlapping halos will rapidly merge, unless there are significant amounts of matter distributed out to a few hundred kpc of the galaxies. This dark matter may either be in distinct halos or more loosely distributed. Large halos would allow pairs at initially large separations to head toward merger, replenishing the distribution at small separations. In the context of this model, the authors estimate that roughly 10 to 25 percent of these low density galaxies are the product of a merger, compared with the elliptical/SO fraction of 18 percent, observed in low density regions of the sample.

  20. Automated and Multiplexed Soft Lithography for the Production of Low-Density DNA Microarrays.

    PubMed

    Fredonnet, Julie; Foncy, Julie; Cau, Jean-Christophe; Séverac, Childérick; François, Jean Marie; Trévisiol, Emmanuelle

    2016-09-26

    Microarrays are established research tools for genotyping, expression profiling, or molecular diagnostics in which DNA molecules are precisely addressed to the surface of a solid support. This study assesses the fabrication of low-density oligonucleotide arrays using an automated microcontact printing device, the InnoStamp 40(®). This automate allows a multiplexed deposition of oligoprobes on a functionalized surface by the use of a MacroStamp(TM) bearing 64 individual pillars each mounted with 50 circular micropatterns (spots) of 160 µm diameter at 320 µm pitch. Reliability and reuse of the MacroStamp(TM) were shown to be fast and robust by a simple washing step in 96% ethanol. The low-density microarrays printed on either epoxysilane or dendrimer-functionalized slides (DendriSlides) showed excellent hybridization response with complementary sequences at unusual low probe and target concentrations, since the actual probe density immobilized by this technology was at least 10-fold lower than with the conventional mechanical spotting. In addition, we found a comparable hybridization response in terms of fluorescence intensity between spotted and printed oligoarrays with a 1 nM complementary target by using a 50-fold lower probe concentration to produce the oligoarrays by the microcontact printing method. Taken together, our results lend support to the potential development of this multiplexed microcontact printing technology employing soft lithography as an alternative, cost-competitive tool for fabrication of low-density DNA microarrays.

  1. Automated and Multiplexed Soft Lithography for the Production of Low-Density DNA Microarrays.

    PubMed

    Fredonnet, Julie; Foncy, Julie; Cau, Jean-Christophe; Séverac, Childérick; François, Jean Marie; Trévisiol, Emmanuelle

    2016-01-01

    Microarrays are established research tools for genotyping, expression profiling, or molecular diagnostics in which DNA molecules are precisely addressed to the surface of a solid support. This study assesses the fabrication of low-density oligonucleotide arrays using an automated microcontact printing device, the InnoStamp 40(®). This automate allows a multiplexed deposition of oligoprobes on a functionalized surface by the use of a MacroStamp(TM) bearing 64 individual pillars each mounted with 50 circular micropatterns (spots) of 160 µm diameter at 320 µm pitch. Reliability and reuse of the MacroStamp(TM) were shown to be fast and robust by a simple washing step in 96% ethanol. The low-density microarrays printed on either epoxysilane or dendrimer-functionalized slides (DendriSlides) showed excellent hybridization response with complementary sequences at unusual low probe and target concentrations, since the actual probe density immobilized by this technology was at least 10-fold lower than with the conventional mechanical spotting. In addition, we found a comparable hybridization response in terms of fluorescence intensity between spotted and printed oligoarrays with a 1 nM complementary target by using a 50-fold lower probe concentration to produce the oligoarrays by the microcontact printing method. Taken together, our results lend support to the potential development of this multiplexed microcontact printing technology employing soft lithography as an alternative, cost-competitive tool for fabrication of low-density DNA microarrays. PMID:27681742

  2. Low-density geochemical mapping and the robustness of geochemical patterns

    USGS Publications Warehouse

    Smith, D.B.; Reimann, C.

    2008-01-01

    Geochemical mapping of entire continents and, ultimately, the world is still a challenge for applied geochemists. At sample densities traditionally used for geochemical exploration (1 site per 1-25 km2), geochemical mapping of whole continents is logistically extremely demanding and tremendously expensive. The first low-density geochemical surveys (1 site per 200 km2) were carried out during the late 1960s in Africa. Later surveys conducted in various parts of the world had sample densities ranging from 1 site per 300 km2 to 1 site per 18 000 km2. Although these surveys were deemed successful by the investigators in defining variations in background element content on a regional scale, the scientific community was sceptical that low-density geochemical mapping was possible and would provide useful information. The main area of criticism centred around the concern that at such low sample densities the resulting maps would not be robust, i.e. if the same area were resampled and remapped, different geochemical patterns would emerge. Different examples from the USA, Europe, China and Africa demonstrate that low-density geochemical mapping will result in stable and robust geochemical patterns at the continental scale. Such maps are urgently needed for a wide variety of applications. ?? 2008 AAG/ Geological Society of London.

  3. Aerobic digestion of starch wastewater in a fluidized bed bioreactor with low density biomass support.

    PubMed

    Rajasimman, M; Karthikeyan, C

    2007-05-01

    A solid-liquid-gas, multiphase, fluidized bed bioreactor with low density particles was used in this study to treat the high organic content starch industry wastewater. The characteristics of starch wastewater were studied. It shows high organic content and acidic nature. The performance of a three phase fluidized bed bioreactor with low density biomass support was studied under various average initial substrate concentrations, by varying COD values (2250, 4475, 6730 and 8910 mg/L) and for various hydraulic retention times (8, 16, 24, 32 and 40 h) based on COD removal efficiency. The optimum bed height for the maximum COD reduction was found to be 80 cm. Experiments were carried out in the bioreactor at an optimized bed height, after the formation of biofilm on the surface of low-density particles (density=870 kg/m(3)). Mixed culture obtained from the sludge, taken from starch industry effluent treatment plant, was used as the source for microorganisms. From the results it was observed that increase in initial substrate concentration leads to decrease in COD reduction and COD reduction increases with increase in hydraulic retention time. The optimum COD removal of 93.8% occurs at an initial substrate concentration of 2250 mg/L and for the hydraulic retention time of 24h.

  4. Response of ecosystem metabolism to low densities of spawning Chinook salmon

    USGS Publications Warehouse

    Benjamin, Joseph R.; Bellmore, James R.; Watson, Grace A.

    2016-01-01

    Marine derived nutrients delivered by large runs of returning salmon are thought to subsidize the in situ food resources that support juvenile salmon. In the Pacific Northwest, USA, salmon have declined to <10% of their historical abundance, with subsequent declines of marine derived nutrients once provided by large salmon runs. We explored whether low densities (<0.001 spawners/m2) of naturally spawning Chinook Salmon (Oncorhynchus tshawytscha) can affect ecosystem metabolism. We measured gross primary production (GPP) and ecosystem respiration (ER) continuously before, during, and after salmon spawning. We compared downstream reaches with low densities of spawning salmon to upstream reaches with fewer or no spawners in 3 mid-sized (4th-order) rivers in northern Washington. In addition, we measured chemical, physical, and biological factors that may be important in controlling rates of GPP and ER. We observed that low densities of spawning salmon can increase GPP by 46% during spawning, but values quickly return to those observed before spawning. No difference in ER was observed between up- and downstream reaches. Based on our results, salmon density, temperature, and the proximity to salmon redds were the most important factors controlling rates of GPP, whereas temperature was most important for ER. These results suggest that even at low spawning densities, salmon can stimulate basal resources that may propagate up the food web. Understanding how recipient ecosystems respond to low levels of marine derived nutrients may inform nutrient augmentation studies aimed at enhancing fish populations.

  5. Protection by polyphenols of postprandial human plasma and low-density lipoprotein modification: the stomach as a bioreactor.

    PubMed

    Kanner, Joseph; Gorelik, Shlomit; Roman, Sirota; Kohen, Ron

    2012-09-12

    Recent studies dramatically showed that the removal of circulating modified low-density lipoprotein (LDL) results in complete prevention of atherosclerosis. The gastrointestinal tract is constantly exposed to food, some of it containing oxidized compounds. Lipid oxidation in the stomach was demonstrated by ingesting heated red meat in rats. Red wine polyphenols added to the rats' meat diet prevented lipid peroxidation in the stomach and absorption of malondialdehyde (MDA) in rat plasma. In humans, postprandial plasma MDA levels rose by 3-fold after a meal of red meat cutlets. MDA derived from meat consumption caused postprandial plasma LDL modification in human. The levels of plasma MDA showed a 75% reduction by consumption of red wine polyphenols during the meat meal. Locating the main biological site of action of polyphenols in the stomach led to a revision in the understanding of how antioxidants work in vivo and may help to elucidate the mechanism involved in the protective effects of polyphenols in human health. PMID:22530973

  6. Low-density lipoprotein antioxidant activity of phenolic compounds and polyphenol oxidase activity in selected clingstone peach cultivars.

    PubMed

    Chang, S; Tan, C; Frankel, E N; Barrett, D M

    2000-02-01

    The antioxidant potential of eight clingstone peach cultivars was investigated by determining phenolic compounds and inhibition of low-density lipoprotein (LDL) oxidation. Cultivars low in polyphenol oxidase (PPO) were also selected to minimize enzymatic browning. Inhibition of LDL oxidation varied from 17.0 to 37.1% in peach flesh extract, from 15.2 to 49.8% in whole peach extract, and from 18.2 to 48.1% in peel extract. Total phenols were 432.8-768.1 mg/kg in flesh extract, 483.3-803.0 mg/kg in whole extract, and 910.9-1922.9 mg/kg in peel extract. The correlation coefficient between relative LDL antioxidant activity and concentration of total phenols was 0.76. Peel PPO activity was higher than flesh activity in most cultivars. The lowest PPO and specific activities were found in the Walgant cultivar, followed by Kakamas and 18-8-23. These three cultivars combine the desirable characteristics of strong antioxidant activity, low PPO activity, and lower susceptibility to browning reactions.

  7. Single Low-Density Lipoprotein Apheresis Does Not Improve Vascular Endothelial Function in Chronically Treated Hypercholesterolemic Patients

    PubMed Central

    Ballard, Kevin D.; Mah, Eunice; Guo, Yi; Bruno, Richard S.; Taylor, Beth A.; Beam, Jo Ellen; Polk, Donna M.; Thompson, Paul D.

    2016-01-01

    Objective. To investigate vascular endothelial function (VEF) responses to a single low-density lipoprotein (LDL) apheresis session in hypercholesterolemic patients undergoing chronic treatment. Methods. We measured brachial artery flow-mediated dilation (FMD), plasma lipids, vitamin E (α- and γ-tocopherol), markers of oxidative/nitrative stress (malondialdehyde (MDA) and nitro-γ-tocopherol (NGT)), and regulators of NO metabolism (arginine (ARG) and asymmetric dimethylarginine (ADMA)) prior to (Pre) and immediately following (Post) LDL apheresis and at 1, 3, 7, and 14 d Post in 5 hypercholesterolemic patients (52 ± 11 y). Results. Relative to Pre, total cholesterol (7.8 ± 1.5 mmol/L) and LDL-cholesterol (6.2 ± 1.2 mmol/L) were 61% and 70% lower (P < 0.01), respectively, at Post and returned to Pre levels at 14 d. Brachial FMD responses (6.9 ± 3.6%) and plasma MDA, ARG, and ADMA concentrations were unaffected by LDL apheresis. Plasma α-tocopherol, γ-tocopherol, and NGT concentrations were 52–69% lower at Post (P < 0.01), and α-tocopherol remained 36% lower at 1 d whereas NGT remained 41% lower at d 3. Conclusions. Acute cholesterol reduction by LDL apheresis does not alter VEF, oxidative stress, or NO homeostasis in patients treated chronically for hypercholesterolemia. PMID:26998360

  8. Hydroxytyrosol in functional hydroxytyrosol-enriched biscuits is highly bioavailable and decreases oxidised low density lipoprotein levels in humans.

    PubMed

    Mateos, Raquel; Martínez-López, Sara; Baeza Arévalo, Gema; Amigo-Benavent, Miryam; Sarriá, Beatriz; Bravo-Clemente, Laura

    2016-08-15

    Hydroxytyrosol (HT) and its derivatives in olive oil protect low-density lipoproteins (LDL) against oxidation. Biscuits could be a convenient alternative to broaden consumers' choice of HT-rich foods, although the biscuit matrix could affect HT bioavailability. We performed a crossover, randomized, double-blind study to evaluate HT bioavailability in HT-enriched biscuits (HT-B) versus non-enriched biscuits (C-B), and the effects on oxidative postprandial status. On two separate days, 13 subjects consumed 30 g of C-B or HT-B (5.25mg HT) after overnight-fasting. Blood and urine were collected at different intervals and analysed by LC-MS-QToF. After HT-B consumption, plasma metabolites peaked between 0.5 and 1h and were extensively excreted in urine. HT-sulphate and 3,4-dihydroxyphenylacetic acid (DOPAC)-sulphate were the main metabolites, followed by DOPAC and homovanillic acid (HVA). HT-glucuronide, DOPAC-glucuronide, HVA-glucuronide and HVA-sulphate were also detected. Postprandial oxidised-LDL concentrations decreased with HT-B. HT is a promising functional ingredient and, in biscuits, it is highly bioavailable and lowers postprandial oxidised-LDL levels. PMID:27006237

  9. [THE LIPOLYSIS IN PHYLOGENETICALLY EARLY LIPOPROTEINS OF LOW DENSITY AND MORE LATER LIPOPROTEINS OF VERY LOW DENSITY: FUNCTION AND DIAGNOSTIC VALUE OF APOE AND APOC-III].

    PubMed

    Rozhkova, T A; Titov, V N; Amelyushkina, V A; Kaba, S I; Kukhartchuk, V V

    2015-12-01

    According to phylogenetic theory of general pathology, the function of low density lipoproteins (LDL) and hydrolysis of triglycerides (TG) in them under the effect of hepatic glycerol hydrolase apoC-III (HGH) developed at much earlier stages of phylogenesis than functioning of insulin-dependent phylogenetically late very low density lipoproteins (VLDL). For millions ofyears, lipolysis and HGH+apoC-III have activated transfer of polyenic fatty acids (FA) in the form of cholesteryl polyesters (CLE) from high density lipoproteins (HDL) to linoleic and linolenic LDL under the effect of cholesteryl ester transfer protein. It is reasonable to suggest that hepatocytes physiologically secrete oleic and palmitic VLDL and linoleic and linolenic LDL. Cells uptake ligand oleic and palmitic VLVL by apoE/B-100 receptor-mediated endocytosis. Physiologically, VLDL are not converted to LDL. If hepatocytes secrete palmitic VLDL in greater amounts than oleic VLDL upon slow hydrolysis ofpalmitic TG and under the effect of postheparinic lipoprotein lipase+apoC-II, only some proportion of palmitic TG is uptaken by cells as VLDL, and the rest is converted in ligand-free palmitic LDL These LDL increase plasma contents of TG and LDL-cholesterol and form small dense palmitic LDL. Expression of HGH+apoC-III synthesis compensates TG hydrolysis in nonphysiological palmitic LDL. In vivo, apoC-III is neither physiological no pathological inhibitor of lipolysis. Increase in plasma apoC-III content is an indicator of accumulation of non-physiological palmitic LDL and atherosclerosis-atheromatosis risk factor ApoE content ofpalmitic LDL increases together with apoC-III, i.e., apoE in ligand VLDL is not internalized via apoE/B-100 endocytosis. An increase in apoC-III and apoE contents are reliable in vivo tests for the rise inpalmitic FA, palmitic TG and excessive secretion of palmitic VLDL by hepatocytes. ApoC-III and apoE contents in LDL are additional tests to evaluate the efficiency of

  10. [THE LIPOLYSIS IN PHYLOGENETICALLY EARLY LIPOPROTEINS OF LOW DENSITY AND MORE LATER LIPOPROTEINS OF VERY LOW DENSITY: FUNCTION AND DIAGNOSTIC VALUE OF APOE AND APOC-III].

    PubMed

    Rozhkova, T A; Titov, V N; Amelyushkina, V A; Kaba, S I; Kukhartchuk, V V

    2015-12-01

    According to phylogenetic theory of general pathology, the function of low density lipoproteins (LDL) and hydrolysis of triglycerides (TG) in them under the effect of hepatic glycerol hydrolase apoC-III (HGH) developed at much earlier stages of phylogenesis than functioning of insulin-dependent phylogenetically late very low density lipoproteins (VLDL). For millions ofyears, lipolysis and HGH+apoC-III have activated transfer of polyenic fatty acids (FA) in the form of cholesteryl polyesters (CLE) from high density lipoproteins (HDL) to linoleic and linolenic LDL under the effect of cholesteryl ester transfer protein. It is reasonable to suggest that hepatocytes physiologically secrete oleic and palmitic VLDL and linoleic and linolenic LDL. Cells uptake ligand oleic and palmitic VLVL by apoE/B-100 receptor-mediated endocytosis. Physiologically, VLDL are not converted to LDL. If hepatocytes secrete palmitic VLDL in greater amounts than oleic VLDL upon slow hydrolysis ofpalmitic TG and under the effect of postheparinic lipoprotein lipase+apoC-II, only some proportion of palmitic TG is uptaken by cells as VLDL, and the rest is converted in ligand-free palmitic LDL These LDL increase plasma contents of TG and LDL-cholesterol and form small dense palmitic LDL. Expression of HGH+apoC-III synthesis compensates TG hydrolysis in nonphysiological palmitic LDL. In vivo, apoC-III is neither physiological no pathological inhibitor of lipolysis. Increase in plasma apoC-III content is an indicator of accumulation of non-physiological palmitic LDL and atherosclerosis-atheromatosis risk factor ApoE content ofpalmitic LDL increases together with apoC-III, i.e., apoE in ligand VLDL is not internalized via apoE/B-100 endocytosis. An increase in apoC-III and apoE contents are reliable in vivo tests for the rise inpalmitic FA, palmitic TG and excessive secretion of palmitic VLDL by hepatocytes. ApoC-III and apoE contents in LDL are additional tests to evaluate the efficiency of

  11. N-Succinyl-chitosan nanoparticles coupled with low-density lipoprotein for targeted osthole-loaded delivery to low-density lipoprotein receptor-rich tumors

    PubMed Central

    Zhang, Chun-ge; Zhu, Qiao-ling; Zhou, Yi; Liu, Yang; Chen, Wei-liang; Yuan, Zhi-Qiang; Yang, Shu-di; Zhou, Xiao-feng; Zhu, Ai-jun; Zhang, Xue-nong; Jin, Yong

    2014-01-01

    N-Succinyl-chitosan (NSC) was synthesized and NSC nanoparticles (NPs) with loaded osthole (Ost) (Ost/NSC-NPs) were prepared by emulsion solvent diffusion. Subsequently, low-density lipoprotein (LDL)-mediated NSC-NPs with loaded Ost (Ost/LDL-NSC-NPs) were obtained by coupling LDL with Ost/NSC-NPs through amide linkage. The average particle size of Ost/NSC-NPs was approximately 145 nm, the entrapment efficiency was 78.28%±2.06%, and the drug-loading amount was 18.09%±0.17%. The release of Ost from Ost/NSC-NPs in vitro showed a more evident sustained effect than the native material. The half maximal inhibitory concentration of Ost/LDL-NSC-NPs was only 16.23% that of the free Ost at 24 hours in HepG2 cells. Ost inhibited HepG2 cell proliferation by arresting cells in the synthesis phase of the cell cycle and by triggering apoptosis. Cellular uptake and subcellular localization in vitro and near-infrared fluorescence real-time imaging in vivo showed that Ost/LDL-NSC-NPs had high targeting efficacy. Therefore, LDL-NSC-NPs are a promising system for targeted Ost delivery to liver tumor. PMID:24966673

  12. Biodegradation of Low-Density Polyethylene (LDPE) by Mixed Culture of Lysinibacillus xylanilyticus and Aspergillus niger in Soil

    PubMed Central

    Esmaeili, Atefeh; Pourbabaee, Ahmad Ali; Alikhani, Hossein Ali; Shabani, Farzin; Esmaeili, Ensieh

    2013-01-01

    In this study, two strains of Aspergillus sp. and Lysinibacillus sp. with remarkable abilities to degrade low-density polyethylene (LDPE) were isolated from landfill soils in Tehran using enrichment culture and screening procedures. The biodegradation process was performed for 126 days in soil using UV- and non-UV-irradiated pure LDPE films without pro-oxidant additives in the presence and absence of mixed cultures of selected microorganisms. The process was monitored by measuring the microbial population, the biomass carbon, pH and respiration in the soil, and the mechanical properties of the films. The carbon dioxide measurements in the soil showed that the biodegradation in the un-inoculated treatments were slow and were about 7.6% and 8.6% of the mineralisation measured for the non-UV-irradiated and UV-irradiated LDPE, respectively, after 126 days. In contrast, in the presence of the selected microorganisms, biodegradation was much more efficient and the percentages of biodegradation were 29.5% and 15.8% for the UV-irradiated and non-UV-irradiated films, respectively. The percentage decrease in the carbonyl index was higher for the UV-irradiated LDPE when the biodegradation was performed in soil inoculated with the selected microorganisms. The percentage elongation of the films decreased during the biodegradation process. The Fourier transform infra-red (FT-IR), x-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to determine structural, morphological and surface changes on polyethylene. These analyses showed that the selected microorganisms could modify and colonise both types of polyethylene. This study also confirmed the ability of these isolates to utilise virgin polyethylene without pro-oxidant additives and oxidation pretreatment, as the carbon source. PMID:24086254

  13. Beneficial effect of Lisosan G on cultured human microvascular endothelial cells exposed to oxidised low density lipoprotein

    PubMed Central

    Lubrano, Valter; Baldi, Simona; Napoli, Debora; Longo, Vincenzo

    2012-01-01

    Background & objectives: Nutritional compounds which display anti-inflammatory and antioxidant effects have specific applications in preventing oxidative stress and endothelial dysfunction. In this study we evaluated the effect of Lisosan G (powder of Triticum sativum grains) on human microvascular endothelial cells (HMEC-1) exposed to oxidized low density lipoprotein (ox-LDL). Methods: The protective effects of Lisosan G were evaluated on human microvascular endothelial cells exposed to ox-LDL. Intercellular adhesion molecular-1 (ICAM-1), endothelin-1 (ET-1), and interleukin-6 (IL-6) concentrations and the expression of the respective genes were evaluated in response to incubation with ox-LDL, after co-incubation with ox-LDL and Lisosan G or exposed to Lisosan G alone. The analysis of LOX-1 gene was performed with RT-PCR semi quantitative method. The degree of oxidation induced in relation to control, was established by measurement of malondialdehyde (MDA) production. Results: The incubation with ox-LDL induced a significant increase in ICAM-1, IL-6 and ET-1 levels compared to the basal condition (P<0.01, P<0.05, and P<0.01, respectively), while in presence of Lisosan G, ICAM-1 levels showed a significant reduction both compared to the cultures treated with ox-LDL and control (P<0.01). IL-6 levels did not show any difference; ET-1 levels showed a partial reduction after co-treatment with Lisosan G, and also with Lisosan G alone, reduced the concentration below control (P<0.01). The modulation of these markers was confirmed by RT-PCR analysis. An association between MDA formation and the three markers production was observed. Semi-quantitative analysis of LOX-1 gene expression showed a significant up-regulation only after ox-LDL exposure. Interpretation & conclusions: The results demonstrate that Lisosan G may have an important role in the prevention of microcirculatory dysfunction. PMID:22885268

  14. Synergistic effect of calcium stearate and photo treatment on the rate of biodegradation of low density polyethylene spent saline vials.

    PubMed

    Carol, D; Karpagam, S; Kingsley, S J; Vincent, S

    2012-07-01

    The biodegradation of spent saline bottles, a low density polyethylene product (LDPE) by two selected Arthrobacter sp. under in vitro conditions is reported. Chemical and UV pretreatment play a vital role in enhancing the rate of biodegradation. Treated LDPE film exhibits a higher weight loss and density when compared to untreated films. Arthrobacter oxydans and Arthrobacter globiformis grew better in medium containing pretreated film than in medium containing untreated film. The decrease in density and weight loss of LDPE was also more for pretreated film when compared to untreated film indicating the affect of abiotic treatment on mechanical properties of LDPE. The decrease in the absorbance corresponding to carbonyl groups and double bonds that were generated during pretreatment suggest that some of the double bonds were cut by Arthrobacter species. Since Arthrobacter sp. are capable of degrading urea, splitting of urea group were also seen in FTIR spectrum indicating the evidence of biodegradation after microbial incubation. The results indicated that biodegradation rate could be enhanced by exposing LDPE to calcium stearate (a pro-oxidant) which acts as an initiator for the oxidation of the polymers leading to a decrease of molecular weight and formation of hydrophilic group. Therefore, the initial step for biodegradation of many inert polymers depends on a photo-oxidation of those polymers. The application in sufficient details with improved procedures utilizing recombinant microorganism with polymer degradation capacity can lead to a better plastic waste management in biomedical field. The present plastic disposal trend of waste accumulation can be minimized with this promising eco-friendly technique. PMID:22822530

  15. Biodegradation of low-density polyethylene (LDPE) by mixed culture of Lysinibacillus xylanilyticus and Aspergillus niger in soil.

    PubMed

    Esmaeili, Atefeh; Pourbabaee, Ahmad Ali; Alikhani, Hossein Ali; Shabani, Farzin; Esmaeili, Ensieh

    2013-01-01

    In this study, two strains of Aspergillus sp. and Lysinibacillus sp. with remarkable abilities to degrade low-density polyethylene (LDPE) were isolated from landfill soils in Tehran using enrichment culture and screening procedures. The biodegradation process was performed for 126 days in soil using UV- and non-UV-irradiated pure LDPE films without pro-oxidant additives in the presence and absence of mixed cultures of selected microorganisms. The process was monitored by measuring the microbial population, the biomass carbon, pH and respiration in the soil, and the mechanical properties of the films. The carbon dioxide measurements in the soil showed that the biodegradation in the un-inoculated treatments were slow and were about 7.6% and 8.6% of the mineralisation measured for the non-UV-irradiated and UV-irradiated LDPE, respectively, after 126 days. In contrast, in the presence of the selected microorganisms, biodegradation was much more efficient and the percentages of biodegradation were 29.5% and 15.8% for the UV-irradiated and non-UV-irradiated films, respectively. The percentage decrease in the carbonyl index was higher for the UV-irradiated LDPE when the biodegradation was performed in soil inoculated with the selected microorganisms. The percentage elongation of the films decreased during the biodegradation process. The Fourier transform infra-red (FT-IR), x-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to determine structural, morphological and surface changes on polyethylene. These analyses showed that the selected microorganisms could modify and colonise both types of polyethylene. This study also confirmed the ability of these isolates to utilise virgin polyethylene without pro-oxidant additives and oxidation pretreatment, as the carbon source.

  16. Calculation of correction factors for ionization chamber measurements with small fields in low-density media.

    PubMed

    Pisaturo, O; Pachoud, M; Bochud, F O; Moeckli, R

    2012-07-21

    The quantity of interest for high-energy photon beam therapy recommended by most dosimetric protocols is the absorbed dose to water. Thus, ionization chambers are calibrated in absorbed dose to water, which is the same quantity as what is calculated by most treatment planning systems (TPS). However, when measurements are performed in a low-density medium, the presence of the ionization chamber generates a perturbation at the level of the secondary particle range. Therefore, the measured quantity is close to the absorbed dose to a volume of water equivalent to the chamber volume. This quantity is not equivalent to the dose calculated by a TPS, which is the absorbed dose to an infinitesimally small volume of water. This phenomenon can lead to an overestimation of the absorbed dose measured with an ionization chamber of up to 40% in extreme cases. In this paper, we propose a method to calculate correction factors based on the Monte Carlo simulations. These correction factors are obtained by the ratio of the absorbed dose to water in a low-density medium □D(w,Q,V1)(low) averaged over a scoring volume V₁ for a geometry where V₁ is filled with the low-density medium and the absorbed dose to water □D(w,QV2)(low) averaged over a volume V₂ for a geometry where V₂ is filled with water. In the Monte Carlo simulations, □D(w,QV2)(low) is obtained by replacing the volume of the ionization chamber by an equivalent volume of water, according to the definition of the absorbed dose to water. The method is validated in two different configurations which allowed us to study the behavior of this correction factor as a function of depth in phantom, photon beam energy, phantom density and field size.

  17. Does nitrogen gas bubbled through a low density polymer gel dosimeter solution affect the polymerization process?

    PubMed Central

    Shahbazi-Gahrouei, Daryoush; Gholami, Mehrdad; Pourfallah, Tayyeb Allahverdi; Keshtkar, Mohammad

    2015-01-01

    Background: On account of the lower electron density in the lung tissue, the dose distribution in the lung cannot be verified with the existing polymer gel dosimeters. Thus, the aims of this study are to make a low density polymer gel dosimeter and investigate the effect of nitrogen gas bubbles on the R2 responses and its homogeneity. Materials and Methods: Two different types of low density polymer gel dosimeters were prepared according to a composition proposed by De Deene, with some modifications. In the first type, no nitrogen gas was perfused through the gel solution and water. In the second type, to expel the dissolved oxygen, nitrogen gas was perfused through the water and gel solution. The post-irradiation times in the gels were 24 and 5 hours, respectively, with and without perfusion of nitrogen gas through the water and gel solution. Results: In the first type of gel, there was a linear correlation between the doses and R2 responses from 0 to 12 Gy. The fabricated gel had a higher dynamic range than the other low density polymer gel dosimeter; but its background R2 response was higher. In the second type, no difference in R2 response was seen in the dose ranges from 0 to 18 Gy. Both gels had a mass density between 0.35 and 0.45 g.cm-3 and CT values of about -650 to -750 Hounsfield units. Conclusion: It appeared that reactions between gelatin-free radicals and monomers, due to an increase in the gel temperature during rotation in the household mixer, led to a higher R2-background response. In the second type of gel, it seemed that the collapse of the nitrogen bubbles was the main factor that affected the R2-responses. PMID:26015914

  18. Can reduced diameter holes and low-density product improve pre-split results?

    SciTech Connect

    Daley, J.

    1996-12-01

    Highwall stability is an ongoing concern at Navajo Mine since it affects the safety of workers in the pit below. The current pre-splitting method uses 10.625 in. holes loaded with ANFO, decked according to hole depth, to achieve an acceptable degree of highwall stability. Geological problems such as faults and diverse sedimentary horizons have caused highwall failures and have created the desire to find an improved method of pre-splitting. The use of low-density product for pre-splitting was proposed, and tested, to simulate a decoupled charge thus improving energy distribution throughout the borehole. A natural extension of this theory was to use a small diameter borehole to further increase the distribution of blast energy. This test used 6.75 in. diameter boreholes and varied hole spacing from 12 ft. to 18 ft. Multiple charge weights of low-density product were compared to ANFO-loaded control sections. The test showed that small diameter holes and low-density product can produce a stable highwall if the proper hole spacing and powder charge are achieved. A lower level of energy can be used to pre-split with this method but at a slightly higher cost than ANFO in 10.625 in. holes. While this test identified the optimum spacing for 6.75 in. pre-split holes at Navajo Mine and showed promise for improved highwalls in difficult geologic horizons, the optimum spacing and small-diameter load did not produce a better highwall than current methods and will not be used as the standard pre-splitting method at Navajo Mine at this time.

  19. Brittle intermetallic compound makes ultrastrong low-density steel with large ductility.

    PubMed

    Kim, Sang-Heon; Kim, Hansoo; Kim, Nack J

    2015-02-01

    Although steel has been the workhorse of the automotive industry since the 1920s, the share by weight of steel and iron in an average light vehicle is now gradually decreasing, from 68.1 per cent in 1995 to 60.1 per cent in 2011 (refs 1, 2). This has been driven by the low strength-to-weight ratio (specific strength) of iron and steel, and the desire to improve such mechanical properties with other materials. Recently, high-aluminium low-density steels have been actively studied as a means of increasing the specific strength of an alloy by reducing its density. But with increasing aluminium content a problem is encountered: brittle intermetallic compounds can form in the resulting alloys, leading to poor ductility. Here we show that an FeAl-type brittle but hard intermetallic compound (B2) can be effectively used as a strengthening second phase in high-aluminium low-density steel, while alleviating its harmful effect on ductility by controlling its morphology and dispersion. The specific tensile strength and ductility of the developed steel improve on those of the lightest and strongest metallic materials known, titanium alloys. We found that alloying of nickel catalyses the precipitation of nanometre-sized B2 particles in the face-centred cubic matrix of high-aluminium low-density steel during heat treatment of cold-rolled sheet steel. Our results demonstrate how intermetallic compounds can be harnessed in the alloy design of lightweight steels for structural applications and others.

  20. Selective uptake of boronated low-density lipoprotein in melanoma xenografts achieved by diet supplementation.

    PubMed

    Setiawan, Y; Moore, D E; Allen, B J

    1996-12-01

    The lipid core of human plasma low-density lipoprotein (LDL) was extracted using hexane and the LDL reconstituted with the addition of n-octyl-carborane. Biodistribution studies of the boronated LDL were performed in BALB/c mice bearing subcutaneous Harding-Passey melanoma xenografts. When diet supplementation with coconut oil and cholesterol for 21 days and regular dosing with hydrocortisone for 7 days before the studies was used to down-regulate the liver LDL receptors and the adrenal receptors, respectively, the tumour-blood boron concentration ratio of 5:1 was achieved.

  1. Receptor-mediated delivery of photoprotective agents by low-density lipoprotein

    SciTech Connect

    Mosley, S.T.; Yang, Y.L.; Falck, J.R.; Anderson, R.G.W.

    1984-12-01

    Low density lipoprotein (LDL) has been used to deliver toxic molecules to cells by receptor-mediated endocytosis. In these studies, the cholesteryl ester core of LDL was replaced with a lipophilic, toxic molecule. The authors report that photoprotective azo dyes can be stably incorporated into LDL, and that this reconstituted LDL protects cells from the photosensitizing action of pyrene methanol (PM) in a receptor-dependent process. The photoprotective action of the azo dye is due to its ability to scavenge singlet oxygen that is produced by the photosensitive agent in response to UV light.

  2. Preparation and characterization of self-cleaning stable superhydrophobic linear low-density polyethylene

    NASA Astrophysics Data System (ADS)

    Yuan, Zhiqing; Chen, Hong; Zhang, Jide; Zhao, Dejian; Liu, Yuejun; Zhou, Xiaoyuan; Li, Song; Shi, Pu; Tang, Jianxin; Chen, Xin

    2008-12-01

    Porous superhydrophobic linear low-density polyethylene (LLDPE) surface was prepared by a simple method. Its water contact angle and sliding angle were 153±2° and 10°, respectively. After contamination, 99% of the contaminant particles were removed from the superhydrophobic LLDPE surface using artificial rain. The superhydrophobic LLDPE surface showed high stability in the pH range from 2 to 13. When LLDPE samples were stored in ambient environment for one month, their water contact angle and sliding angle remained constant. Their superhydrophobic property was also maintained after annealing in the temperature range 10-90 °C.

  3. A monochromatic x-ray imaging system for characterizing low-density foams

    SciTech Connect

    Lanier, Nicholas E.; Taccetti, Jose M.; Hamilton, Christopher E.

    2012-05-04

    In High Energy Density (HED) laser experiments, targets often require small, low-density, foam components. However, their limited size can preclude single component characterization, forcing one to rely solely on less accurate bulk measurements. We have developed a monochromatic imaging a system to characterize both the density and uniformity of single component low-mass foams. This x-ray assembly is capable of determining line-averaged density variations near the 1% level, and provides statistically identical results to those obtained at the Brookhaven's NSLS. This system has the added benefit of providing two-dimensional density data, allowing an assessment of density uniformity.

  4. Experimental static aerodynamics of a regular hexagonal prism in a low density hypervelocity flow

    NASA Technical Reports Server (NTRS)

    Guy, R. W.; Mueller, J. N.; Lee, L. P.

    1972-01-01

    A regular hexagonal prism, having a fineness ratio of 1.67, has been tested in a wind tunnel to determine its static aerodynamic characteristics in a low-density hypervelocity flow. The prism tested was a 1/4-scale model of the graphite heat shield which houses the radioactive fuel for the Viking spacecraft auxiliary power supply. The basic hexagonal prism was also modified to simulate a prism on which ablation of one of the six side flats had occurred. This modified hexagonal prism was tested to determine the effects on the aerodynamic characteristics of a shape change caused by ablation during a possible side-on stable reentry.

  5. Gravitational Effects on Flow Instability and Transition in Low Density Jets

    NASA Technical Reports Server (NTRS)

    Agrawal A. K.; Parthasarathy, K.; Pasumarthi, K.; Griffin, D. W.

    2000-01-01

    Recent experiments have shown that low-density gas jets injected into a high-density ambient gas undergo an instability mode, leading to highly-periodic oscillations in the flow-field for certain conditions. The transition from laminar to turbulent flow in these jets is abrupt, without the gradual change in scales. Even the fine scale turbulent structure repeats itself with extreme regularity from cycle to cycle. Similar observations were obtained in buoyancy-dominated and momentum-dominated jets characterized by the Richardson numbers, Ri = [gD(rho(sub a)-rho(sub j))/rho(sub j)U(sub j)(exp 2) ] where g is the gravitational acceleration, D is the jet diameter, rho(sub a) and rho(sub a) are, respectively, the free-stream and jet densities, and U(sub j) is the mean jet exit velocity. At high Richardson numbers, the instability is presumably caused by buoyancy since the flow-oscillation frequency (f) or the Strouhal number, St = [fD/U(sub j)] scales with Ri. In momentum-dominated jets, however, the Strouhal number of the oscillating flow is relatively independent of the Ri. In this case, a local absolute instability is predicted in the potential core of low-density jets with S [= rho(sub j)/rho(sub a)] < 0.7, which agrees qualitatively with experiments. Although the instability in gas jets of high Richardson numbers is attributed to buoyancy, direct physical evidence has not been acquired in experiments. If the instability is indeed caused by buoyancy, the near-field flow structure of the jet will change significantly when the buoyancy is removed, for example, in the microgravity environment. Thus, quantitative data on the spatial and temporal evolutions of the instability, length and time scale of the oscillating mode and its effects on the mean flow and breakdown of the potential core are needed in normal and microgravity to delineate gravitational effects in buoyant jets. In momentum dominated low-density jets, the instability is speculated to originate in the

  6. Extreme ultraviolet source at 6.7 nm based on a low-density plasma

    SciTech Connect

    Higashiguchi, Takeshi; Yugami, Noboru; Otsuka, Takamitsu; Jiang, Weihua; Endo, Akira; Li Bowen; Kilbane, Deirdre; Dunne, Padraig; O'Sullivan, Gerry

    2011-11-07

    We demonstrate an efficient extreme ultraviolet (EUV) source for operation at {lambda} = 6.7 nm by optimizing the optical thickness of gadolinium (Gd) plasmas. Using low initial density Gd targets and dual laser pulse irradiation, we observed a maximum EUV conversion efficiency (CE) of 0.54% for 0.6% bandwidth (BW) (1.8% for 2% BW), which is 1.6 times larger than the 0.33% (0.6% BW) CE produced from a solid density target. Enhancement of the EUV CE by use of a low-density plasma is attributed to the reduction of self-absorption effects.

  7. Effect of gamma radiation on low density polyethylene (LDPE) films: optical, dielectric and FTIR studies.

    PubMed

    Moez, A Abdel; Aly, S S; Elshaer, Y H

    2012-07-01

    The low density polyethylene (LDPE) films were irradiated with gamma radiation in the dose range varied from 20 to 400 kGy. The induced changes in the chemical structure and dielectric properties for the irradiated films were investigated. The structure modifications: crystallinity as well as possible molecular changes of the polymer were recognized using Fourier Transform Infrared Spectroscopy (FTIR). The optical results were determined from transmission, reflection and absorption spectra for these films. The dielectric properties of these films were calculated using optical methods. Result indicates small variation in crystallinity which could be increased or decreased depending on the relative importance of the structural and chemical changes.

  8. Determination of antioxidant migration levels from low-density polyethylene films into food simulants.

    PubMed

    Dopico-García, M S; López-Vilariño, J M; González-Rodríguez, M V

    2003-11-01

    An analytical method for the determination of specific migration levels of phenolic antioxidants from low-density polyethylene (LDPE) into food simulant has been developed. The screening and response surface experimental designs to optimize the liquid-liquid extraction (LLE) of these antioxidants have been tested and the analyses have been carried out by reversed-phase high-performance liquid chromatography (HPLC) coupled with ultraviolet diode-array detector. The procedure developed has been applied to specific migration tests in different commercial LDPE films. The considered antioxidants have not been found upper the legislation limits although Ethanox 330 and Irgafos 168 have been found at trace level.

  9. Structured Low-Density Parity-Check Codes with Bandwidth Efficient Modulation

    NASA Technical Reports Server (NTRS)

    Cheng, Michael K.; Divsalar, Dariush; Duy, Stephanie

    2009-01-01

    In this work, we study the performance of structured Low-Density Parity-Check (LDPC) Codes together with bandwidth efficient modulations. We consider protograph-based LDPC codes that facilitate high-speed hardware implementations and have minimum distances that grow linearly with block sizes. We cover various higher- order modulations such as 8-PSK, 16-APSK, and 16-QAM. During demodulation, a demapper transforms the received in-phase and quadrature samples into reliability information that feeds the binary LDPC decoder. We will compare various low-complexity demappers and provide simulation results for assorted coded-modulation combinations on the additive white Gaussian noise and independent Rayleigh fading channels.

  10. Isotope-specific detection of low density materials with mono-energetic (gamma)-rays

    SciTech Connect

    Albert, F; Anderson, S G; Gibson, D J; Hagmann, C A; Johnson, M S; Messerly, M J; Semenov, V A; Shverdin, M Y; Tremaine, A M; Hartemann, F V; Siders, C W; McNabb, D P; Barty, C J

    2009-03-16

    The first demonstration of isotope-specific detection of a low-Z, low density object, shielded by a high-Z and high density material using mono-energetic gamma-rays is reported. Isotope-specific detection of LiH shielded by Pb and Al is accomplished using the nuclear resonance fluorescence line of {sup 7}Li at 0.478 MeV. Resonant photons are produced via laser-based Compton scattering. The detection techniques are general and the confidence level obtained is shown to be superior to that yielded by conventional x-ray/{gamma}-ray techniques in these situations.

  11. Synthetic Nano-Low Density Lipoprotein as Targeted Drug DeliveryVehicle for Glioblastoma Multiforme

    SciTech Connect

    Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu,Xiao; Budinger, Thomas F.; Forte, Trudy M.

    2006-06-14

    This paper discribes a synthetic low density lipoprotein(LDL) made by complexing a 29 amino acid that consists of a lipid bindingdomain and the LDL receptor binding domain with a lipid microemulsion.The nano-LDL particles were intermdiate in size between LDL and HDL andbound to LDL receptors on GBM brain tumor cells. Synthetic nano-LDLuptake by GBM cells was LDL receptor specific and dependent on cellreceptor number. It is suggested that these synthetic particles can serveas a delivery vehicle for hydophobic anti-tumor drugs by targeting theLDL receptor.

  12. Bogolubov-Hartree-Fock Theory for Strongly Interacting Fermions in the Low Density Limit

    NASA Astrophysics Data System (ADS)

    Bräunlich, Gerhard; Hainzl, Christian; Seiringer, Robert

    2016-06-01

    We consider the Bogolubov-Hartree-Fock functional for a fermionic many-body system with two-body interactions. For suitable interaction potentials that have a strong enough attractive tail in order to allow for two-body bound states, but are otherwise sufficiently repulsive to guarantee stability of the system, we show that in the low-density limit the ground state of this model consists of a Bose-Einstein condensate of fermion pairs. The latter can be described by means of the Gross-Pitaevskii energy functional.

  13. High excitation power photoluminescence studies of ultra-low density GaAs quantum dots

    SciTech Connect

    Sonnenberg, D.; Graf, A.; Paulava, V.; Heyn, Ch.; Hansen, W.

    2013-12-04

    We fabricate GaAs epitaxial quantum dots (QDs) by filling of self-organized nanoholes in AlGaAs. The QDs are fabricated under optimized process conditions and have ultra-low density in the 10{sup 6} cm{sup −2} regime. At low excitation power the optical emission of single QDs exhibit sharp excitonic lines, which are attributed to the recombination of excitonic and biexcitonic states. High excitation power measurements reveal surprisingly broad emission lines from at least six QD shell states.

  14. Converging shock generation with cone target filled with low density foam

    NASA Astrophysics Data System (ADS)

    Shigemori, K.; Yamamoto, T.; Hironaka, Y.; Kawashima, T.; Hattori, S.; Nagatomo, H.; Kato, H.; Sato, N.; Watari, T.; Takagi, M.

    2016-05-01

    We have been developing an alternative scheme of fast ignition of inertial confinement targets with converging shock. Experiments were carried out on GEKKO-XII laser facility at ILE, Osaka University. We employed Au cone targets filled with low- density RF foam (2 mg/cm3). The foam-filled cone targets were irradiated by three beams of the GEKKO-XII, with pulse duration of 1.3 ns, intensity of ∼ 1014 W/cm2 in 2 :λ(ω0.527μm). Self-emission at the tip of cone was observed by one-dimensional streaked optical pyrometer (SOP) and two-dimensional images.

  15. Magnetic Resonance Imaging Detection of Tumor Cells by Targeting Low-Density Lipoprotein Receptors with Gd-Loaded Low-Density Lipoprotein Particles1

    PubMed Central

    Crich, Simonetta Geninatti; Lanzardo, Stefania; Alberti, Diego; Belfiore, Simona; Ciampa, Anna; Giovenzana, Giovanni B; Lovazzano, Clara; Pagliarin, Roberto; Aime, Silvio

    2007-01-01

    Gd-DO3A-diph and Gd-AAZTAC17 are lipophilic magnetic resonance imaging (MRI) agents that display high affinity for low-density lipoprotein (LDL) particles. However, on binding to LDL, Gd-DO3A-diph shows a decreased hydration that results in a lower enhancement of water proton relaxation rate. Conversely, Gd-AAZTAC17 displays a strong relaxation enhancement at the imaging fields. Each LDL particle can load up to 100 and 400 UNITS of Gd-DO3A-diph and Gd-AAZTAC17, respectively. Their LDL adducts are taken up by human hepatoblastoma G2 (HepG2) and melanoma B16 tumor cells when added to the incubation medium. T1 measurements of the labeled cells indicate that Gd-AAZTAC17 is significantly more efficient than Gd-DO3A-diph. Furthermore, it has been found that HepG2 hepatoma cells can internalize higher amounts of Gd-AAZTAC17 than B16 cells and the involvement of LDL receptors (LDLRs) has been demonstrated in competition assays with free LDL. Gd-AAZTAC17/LDL adduct proved to be an efficient probe in the magnetic resonance (MR) visualization of subcutaneous tumors in animal models obtained by injecting B16 melanoma cells into the right flank of mice. Finally, confocal microscopy validation of the distribution of LDL-based probes in the tumor has been obtained by doping the Gd-AAZTAC17/LDL adduct with a fluorescent phospholipid moiety. PMID:18084612

  16. Low-density lipoprotein receptor-related protein 1: a physiological Aβ homeostatic mechanism with multiple therapeutic opportunities

    PubMed Central

    Sagare, Abhay P.; Deane, Rashid; Zlokovic, Berislav V.

    2012-01-01

    Low-density lipoprotein receptor-related protein-1 (LRP1) is the main cell surface receptor involved in brain and systemic clearance of the Alzheimer's disease (AD) toxin amyloid-beta (Aβ). In plasma, a soluble form of LRP1 (sLRP1) is the major transport protein for peripheral Aβ. LRP1 in brain endothelium and mural cells mediates Aβ efflux from brain by providing a transport mechanism for A across the blood-brain barrier (BBB). sLRP1 maintains a plasma ‘sink’ activity for Aβ through binding of peripheral Aβ which in turn inhibits re-entry of free plasma Aβ into the brain. LRP1 in the liver mediates systemic clearance of Aβ. In AD, LRP1 expression at the BBB is reduced and Aβ binding to circulating sLRP1 is compromised by oxidation. Cell surface LRP1 and circulating sLRP1 represent druggable targets which can be therapeutically modified to restore the physiological mechanisms of brain Aβ homeostasis. In this review, we discuss how increasing LRP1 expression at the BBB and liver with lifestyle changes, statins, plant-based active principles and/or gene therapy on one hand, and how replacing dysfunctional plasma sLRP1 on the other regulate Aβ clearance from brain ultimately controlling the onset and/or progression of AD. PMID:22820095

  17. The effects of high energy electron beam irradiation on the thermal and structural properties of low density polyethylene

    NASA Astrophysics Data System (ADS)

    Murray, Kieran A.; Kennedy, James E.; McEvoy, Brian; Vrain, Olivier; Ryan, Damien; Higginbotham, Clement L.

    2012-08-01

    Radiation is currently being exploited to modify polyethylene in order to improve properties for various applications such as hip replacements. This paper thoroughly examines the effects of high energy electron beam irradiation (10 MeV) on low density polyethylene (LDPE) material. ASTM (American Society for Testing and Materials) testing specimens were manufactured from LDPE and subjected to a broad range of doses ranging between 25 and 400 kGy at room temperature in an air atmosphere. Extensive characterisation techniques such as modulated differential scanning calorimetry (MDSC) and the Fourier transform infrared spectroscopy (FTIR) were conducted on the non-irradiated and irradiated samples. While considering the semicrystalline nature of LDPE during the MDSC experiment, the melting temperature (Tm) and the temperature crystallinity (Tc) were calculated. This revealed that the Tm and the Tc decreased in temperature as the irradiation dose increased. The FTIR analysis was implemented to evaluate the presence of polar species such as carbonyl groups and trans-vinylene double bond groups. The IR spectra illustrated that the concentration of characteristic bands for trans-vinylene bonds increased with increasing radiation dose indicating the formation of carbonyl bond groups. Furthermore, the results demonstrated an occurrence of oxidative degradation due to the formation of carbonyl groups at 1718 cm-1.

  18. Reactive decomposition of low density PMDI foam subject to shock compression

    NASA Astrophysics Data System (ADS)

    Alexander, Scott; Reinhart, William; Brundage, Aaron; Peterson, David

    Low density polymethylene diisocyanate (PMDI) foam with a density of 5.4 pounds per cubic foot (0.087 g/cc) was tested to determine the equation of state properties under shock compression over the pressure range of 0.58 - 3.4 GPa. This pressure range encompasses a region approximately 1.0-1.2 GPa within which the foam undergoes reactive decomposition resulting in significant volume expansion of approximately three times the volume prior to reaction. This volume expansion has a significant effect on the high pressure equation of state. Previous work on similar foam was conducted only up to the region where volume expansion occurs and extrapolation of that data to higher pressure results in a significant error. It is now clear that new models are required to account for the reactive decomposition of this class of foam. The results of plate impact tests will be presented and discussed including details of the unique challenges associated with shock compression of low density foams. Sandia National Labs is a multi-program lab managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corp., for the U.S. Dept. of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL85000.

  19. Interleukin-10 Deficiency Increases Atherosclerosis, Thrombosis, and Low-density Lipoproteins in Apolipoprotein E Knockout Mice

    PubMed Central

    Caligiuri, Giuseppina; Rudling, Mats; Ollivier, Véronique; Jacob, Marie-Paule; Michel, Jean-Baptiste; Hansson, Göran K; Nicoletti, Antonino

    2003-01-01

    Interleukin (IL)-10 is an anti-inflammatory cytokine that may play a protective role in atherosclerosis. The aim of this study was to assess the effect of IL-10 deficiency in the apolipoprotein E knockout mouse. Apolipoprotein E deficient (E−/−) and IL-10 deficient (−/−) mice were crossed to generate E−/− × IL-10−/− double knockout mice. By 16 wk, cholesterol and triglycerides were similar in double and single knockouts but the lack of IL-10 led to increased low-density lipoprotein cholesterol whereas very-low-density lipoprotein was reduced. In parallel, T-helper 1 responses and lesion size were dramatically increased in double knockout compared with E−/− controls. At 48 wk, matrix metalloproteinases and tissue factor activities were increased in lesions of double-knockout mice. Furthermore, markers of systemic coagulation were increased, and vascular thrombosis in response to i.v. thrombin occurred more frequently in E−/− × IL-10−/− than in E−/− mice. Our findings suggest that IL-10 deficiency plays a deleterious role in atherosclerosis. The early phase of lesion development was increased, and the proteolytic and procoagulant activity was elevated in advanced lesions. These data show that IL-10 may reduce atherogenesis and improve the stability of plaques. PMID:12765335

  20. Fast magnetic reconnection in low-density electron-positron plasmas

    SciTech Connect

    Bessho, Naoki; Bhattacharjee, A.

    2010-10-15

    Two-dimensional particle-in-cell simulations have been performed to study magnetic reconnection in low-density electron-positron plasmas without a guide magnetic field. Impulsive reconnection rates become of the order of unity when the background density is much smaller than 10% of the density in the initial current layer. It is demonstrated that the outflow speed is less than the upstream Alfven speed, and that the time derivative of the density must be taken into account in the definition of the reconnection rate. The reconnection electric fields in the low-density regime become much larger than the ones in the high-density regime, and it is possible to accelerate the particles to high energies more efficiently. The inertial term in the generalized Ohm's law is the most dominant term that supports a large reconnection electric field. An effective collisionless resistivity is produced and tracks the extension of the diffusion region in the late stage of the reconnection dynamics, and significant broadening of the diffusion region is observed. Because of the broadening of the diffusion region, no secondary islands, which have been considered to play a role to limit the diffusion region, are generated during the extension of the diffusion region in the outflow direction.

  1. Linkage between cholesterol 7alpha-hydroxylase and high plasma low-density lipoprotein cholesterol concentrations.

    PubMed Central

    Wang, J; Freeman, D J; Grundy, S M; Levine, D M; Guerra, R; Cohen, J C

    1998-01-01

    Interindividual differences in plasma low-density lipoprotein cholesterol (LDL-C) levels reflect both environmental variation and genetic polymorphism, but the specific genes involved and their relative contributions to the variance in LDL-C are not known. In this study we investigated the relationship between plasma LDL-C concentrations and three genes with pivotal roles in LDL metabolism: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and cholesterol 7alpha-hydroxylase (CYP7). Analysis of 150 nuclear families indicated statistically significant linkage between plasma LDL-C concentrations and CYP7, but not LDLR or APOB. Further sibling pair analyses using individuals with high plasma LDL-C concentrations as probands indicated that the CYP7 locus was linked to high plasma LDL-C, but not to low plasma LDL-C concentrations. This finding was replicated in an independent sample. DNA sequencing revealed two linked polymorphisms in the 5' flanking region of CYP7. The allele defined by these polymorphisms was associated with increased plasma LDL-C concentrations, both in sibling pairs and in unrelated individuals. Taken together, these findings indicate that polymorphism in CYP7 contributes to heritable variation in plasma LDL-C concentrations. Common polymorphisms in LDLR and APOB account for little of the heritable variation in plasma LDL-C concentrations in the general population. PMID:9502769

  2. Apolipoprotein E on Hepatitis C Virion Facilitates Infection through Interaction with Low Density Lipoprotein Receptor

    PubMed Central

    Owen, David M.; Huang, Hua; Ye, Jin; Gale, Michael

    2009-01-01

    Hepatitis C virus (HCV) infection is a major cause of liver disease. HCV associates with host apolipoproteins and enters hepatocytes through complex processes involving some combination of CD81, claudin-I, occludin, and scavenger receptor BI. Here we show that infectious HCV resembles very low density lipoprotein (VLDL) and that entry involves co-receptor function of the low density lipoprotein receptor (LDL-R). Blocking experiments demonstrate that β-VLDL itself or anti-apolipoprotein E (apoE) antibody can block HCV entry. Knockdown of the LDL-R by treatment with 25-hydroxycholesterol or siRNA ablated ligand uptake and reduced HCV infection of cells, whereas infection was rescued upon cell ectopic LDL-R expression. Analyses of gradient-fractionated HCV demonstrate that apoE is associated with HCV virions exhibiting peak infectivity and dependence upon the LDL-R for cell entry. Our results define the LDL-R as a cooperative HCV co-receptor that supports viral entry and infectivity through interaction with apoE ligand present in an infectious HCV/lipoprotein complex comprising the virion. Disruption of HCV/LDL-R interactions by altering lipoprotein metabolism may therefore represent a focus for future therapy. PMID:19751943

  3. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice.

    PubMed Central

    Harris, H W; Grunfeld, C; Feingold, K R; Rapp, J H

    1990-01-01

    Endotoxemia stimulates many physiologic responses including disturbances in lipid metabolism. We hypothesized that this lipemia may be part of a defensive mechanism by which the body combats the toxic effects of circulating endotoxin. We tested the effects of mixtures of endotoxin, lipoproteins, and lipoprotein-free plasma and determined the ability of varying concentrations of human very low density lipoproteins (VLDL) and chylomicrons, as well as low density lipoproteins (LDL) and high density lipoproteins (HDL), and of the synthetic lipid emulsion SOYACAL to prevent endotoxin-induced death in mice. This study demonstrates that the triglyceride-rich VLDL and chylomicrons, as well as cholesterol-rich LDL and HDL, and cholesterol-free SOYACAL can protect against endotoxin-induced death. Protection required small amounts of lipoprotein-free plasma, and depended on the incubation time and the concentration of lipoprotein lipid. Despite stringent techniques to prevent exogenous endotoxin contamination eight of ten duplicate VLDL preparations contained endotoxin (5,755 +/- 3,514 ng endotoxin/mg triglyceride, mean +/- SEM) making the isolation of endotoxin-free VLDL difficult. In contrast, simultaneous preparations of LDL and HDL were relatively free of endotoxin contamination (3 +/- 3 and 320 +/- 319 ng/mg total cholesterol, respectively), suggesting that the contamination of VLDL occurs in vivo and not during the isolation procedure. These observations suggest a possible role for increased triglyceride-rich lipoproteins in the host's defense against endotoxemia and infection. Images PMID:2394827

  4. Monitoring polynuclear aromatic hydrocarbons in aqueous environments with passive low-density polyethylene membrane devices.

    PubMed

    Carls, Mark G; Holland, Larry G; Short, Jeffrey W; Heintz, Ron A; Rice, Stanley D

    2004-06-01

    Low-density polyethylene membranes, typically filled with triolein, have been previously deployed as passive environmental samplers designed to accumulate nonpolar hydrophobic chemicals from water, sediments, and air. Hydrocarbons in such samplers, known as semipermeable membrane devices (SPMDs), diffuse through pores in the membranes and are trapped in the central hydrocarbon matrix, mimicking uptake by living organisms. Here, we describe laboratory and field verification that low-density polyethylene membrane devices (PEMDs) without triolein provide reliable, relatively inexpensive, time-integrated hydrocarbon sampling from water. For comparison, polynuclear aromatic hydrocarbon (PAH) uptake in SPMDs and pink salmon eggs also was studied. Total concentrations of PAH accumulated by PEMDs were highly correlated with concentrations in water (r2 > or = 0.99) and linear over the range tested (0-17 microg/L). Higher-molecular-mass PAH preferentially accumulated in PEMDs and in pink salmon eggs, but the source of oil in PEMDs remained identifiable. Accumulations of PAH were highly similar to those in SPMDs. The PEMDs retained approximately 78% of accumulated total PAH for 40 d in clean water. Thus, a simple plastic membrane can be conveniently used for environmental monitoring, particularly during situations in which contaminant concentrations are low (in the parts-per-billion range), variable, and intermittent.

  5. Ordering of low-density Ge quantum dot on patterned Si substrate

    NASA Astrophysics Data System (ADS)

    Ma, Y. J.; Zeng, C.; Zhou, T.; Huang, S. F.; Fan, Y. L.; Zhong, Z.; Yang, X. J.; Xia, J. S.; Jiang, Z. M.

    2014-12-01

    We present a study on the growth of a low-density ordered Ge quantum dot (QD) on a nanohole patterned Si (0 0 1) substrate with periods in the order of microns by molecular beam epitaxy. Ordered Ge QDs with different periods were realized, the largest period being 15 µm. From the height-profile evolution of the QD with Ge deposition, it was found that the nanohole filling started at the initial Ge deposition, indicating an immediate nucleation and growth of QDs inside the nanoholes. Such a phenomenon is attributed to a lower surface chemical potential (SCP) inside the nanoholes, which is supported by calculated results on SCP evolution with growth and verified by the observation that the Ge adatoms around the nanoholes exhibited a higher probability of being incorporated into the nanoholes. In this scenario, low density ordered Ge QDs with any large periods could be achieved. The optical properties of the Ge QDs showed a remarkable improvement after a post-growth rapid thermal annealing treatment.

  6. Practical technique to quantify small, dense low-density lipoprotein cholesterol using dynamic light scattering

    NASA Astrophysics Data System (ADS)

    Trirongjitmoah, Suchin; Iinaga, Kazuya; Sakurai, Toshihiro; Chiba, Hitoshi; Sriyudthsak, Mana; Shimizu, Koichi

    2016-04-01

    Quantification of small, dense low-density lipoprotein (sdLDL) cholesterol is clinically significant. We propose a practical technique to estimate the amount of sdLDL cholesterol using dynamic light scattering (DLS). An analytical solution in a closed form has newly been obtained to estimate the weight fraction of one species of scatterers in the DLS measurement of two species of scatterers. Using this solution, we can quantify the sdLDL cholesterol amount from the amounts of the low-density lipoprotein cholesterol and the high-density lipoprotein (HDL) cholesterol, which are commonly obtained through clinical tests. The accuracy of the proposed technique was confirmed experimentally using latex spheres with known size distributions. The applicability of the proposed technique was examined using samples of human blood serum. The possibility of estimating the sdLDL amount using the HDL data was demonstrated. These results suggest that the quantitative estimation of sdLDL amounts using DLS is feasible for point-of-care testing in clinical practice.

  7. Low-Density Nozzle Flow by the Direct Simulation Monte Carlo and Continuum Methods

    NASA Technical Reports Server (NTRS)

    Chung, Chang-Hong; Kim, Sku C.; Stubbs, Robert M.; Dewitt, Kenneth J.

    1994-01-01

    Two different approaches, the direct simulation Monte Carlo (DSMC) method based on molecular gasdynamics, and a finite-volume approximation of the Navier-Stokes equations, which are based on continuum gasdynamics, are employed in the analysis of a low-density gas flow in a small converging-diverging nozzle. The fluid experiences various kinds of flow regimes including continuum, slip, transition, and free-molecular. Results from the two numerical methods are compared with Rothe's experimental data, in which density and rotational temperature variations along the centerline and at various locations inside a low-density nozzle were measured by the electron-beam fluorescence technique. The continuum approach showed good agreement with the experimental data as far as density is concerned. The results from the DSMC method showed good agreement with the experimental data, both in the density and the rotational temperature. It is also shown that the simulation parameters, such as the gas/surface interaction model, the energy exchange model between rotational and translational modes, and the viscosity-temperature exponent, have substantial effects on the results of the DSMC method.

  8. A mutualism-parasitism system modeling host and parasite with mutualism at low density.

    PubMed

    Wang, Yuanshi; Deangelis, Donald L

    2012-04-01

    A mutualism-parasitism system of two species is considered, where mutualism is the dominant interaction when the predators (parasites) are at low density while parasitism is dominant when the predators are at high density. Our aim is to show that mutualism at low density promotes coexistence of the species and leads to high production of the prey (host). The mutualism-parasitism system presented here is a combination of the Lotka-Volterra cooperative model and Lotka-Volterra predator-prey model. By comparing dynamics of this system with those of the Lotka-Volterra predator-prey model, we present the mechanisms by which the mutualism improves the coexistence of the species and production of the prey. Then the parameter space is divided into six regions, which correspond to the four outcomes of mutualism, commensalism, predation/parasitism and neutralism, respectively. When the parameters are varied continuously among the six regions, it is shown that the interaction outcomes of the system transition smoothly among the four outcomes. By comparing the dynamics of the specific system with those of the Lotka-Volterra cooperative model, we show that the parasitism at high density promotes stability of the system. A novel aspect of this paper is the simplicity of the model, which allows rigorous and thorough analysis and transparency of the results.

  9. Amphiphilic polyvinyl alcohol adsorbent for the removal of low-density lipoprotein.

    PubMed

    Yu, Yao Ting; Zhu, Huijun; Wang, Shenqi

    2015-04-01

    Spacer can effectively reduce the steric hindrance and synergistic effect of the hydrophilic and hydrophobic ligands immobilized in adsorbents can improve the specific adsorption for low-density lipoprotein (LDL). In this paper, in order to improve the adsorption capacity for the Low-density lipoprotein-cholesterol (LDL-C), specifically, amphiphilic adsorbent based on polyvinyl alcohol (PVA) containing cholesterol ligand and sulfonic dextran ligands was synthesized. All kinds of factors affecting the synthesis yield and adsorption properties were studied in detail. Results showed that the amphiphilic PVA adsorbent has higher adsorption capacity for total cholesterol (TC), (LDL-C), triglyceride (TG), and lower adsorption capacity, and percentage for high-density lipoprotein-cholesterol (HDL-C), while the ligand ratio of cholesterol to sulfonic ligands is 1.57:1, the adsorption percentage and adsorption capacity for TC, LDL-C, TG, and HDL-C were 54.4%, 67.6%, 42.5%, 10.4% and 4.02, 3.612, 2.154, 0.168 mg/g, respectively.

  10. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol.

    PubMed

    Della Badia, Laura A; Elshourbagy, Nabil A; Mousa, Shaker A

    2016-08-01

    Statins and other lipid-lowering drugs have dominated the market for many years for achievement of recommended levels of low-density lipoprotein cholesterol (LDL-C). However, a substantial number of high-risk patients are unable to achieve the LDL-C goal. Proprotein convertase subtilisin/kexin 9 (PCSK9) has recently emerged as a new, promising key therapeutic target for hypercholesterolemia. PCSK9 is a protease involved in chaperoning the low-density lipoprotein receptor to the process of degradation. PCSK9 inhibitors and statins effectively lower LDL-C. The PCSK9 inhibitors decrease the degradation of the LDL receptors, whereas statins mainly interfere with the synthetic machinery of cholesterol by inhibiting the key rate limiting enzyme, the HMG CoA reductase. PCSK9 inhibitors are currently being developed as monoclonal antibodies for their primary use in lowering LDL-C. They may be especially useful for patients with homozygous familial hypercholesterolemia, who at present receive minimal benefit from traditional statin therapy. The monoclonal antibody PCSK9 inhibitors, recently granted FDA approval, show the most promising safety and efficacy profile compared to other, newer LDL-C lowering therapies. This review will primarily focus on the safety and efficacy of monoclonal antibody PCSK9 inhibitors in comparison to statins. The review will also address new, alternative PCSK9 targeting drug classes such as small molecules, gene silencing agents, apolipoprotein B antisense oligonucleotides, and microsomal triglyceride transfer protein inhibitors.

  11. Preparation of highly uniform low density polystyrene foams and their characterization

    SciTech Connect

    Steckle, W. P. , Jr.; Smith, M. E.; Sebring, R. J.; Wilson, K. V.; Nobile, A. , Jr.

    2004-01-01

    High Internal Phase Emulsion polystyrene foams have been made at Los Alamos National Laboratory for the past decade. As target designs become more complex the demands placed on the foams are more stringent. Parts need to be machined from 30 mg/cm{sup 3} foams to a thickness of 50 {micro}m within a couple of microns. Containing upwards of 97% air, these foams are to withstand extraction with ethanol to remove the wax utilized as a machining aid yet retain their dimensional stability. At low densities, less than 50 mg/cm{sup 3}, voids are a problem. To determine a formulation that reduces void content and allows minimum shrinkage, experimental design was utilized. We also developed image analysis techniques that allow us to quantify the amount of voids in the system and the surface finish of the foam. In order to machine these low density foams to the tolerance required with an optimum surface finish, the foams are backfilled with Brij{reg_sign} 78, an alcohol soluble wax. After a part is machined the Brij{reg_sign} is leached out with ethanol. The dimensional stability of the foam was found to be independent of the formulation of the foam. The filler that was used to aid in machining did have a significant impact on the final properties of a machined part.

  12. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol.

    PubMed

    Della Badia, Laura A; Elshourbagy, Nabil A; Mousa, Shaker A

    2016-08-01

    Statins and other lipid-lowering drugs have dominated the market for many years for achievement of recommended levels of low-density lipoprotein cholesterol (LDL-C). However, a substantial number of high-risk patients are unable to achieve the LDL-C goal. Proprotein convertase subtilisin/kexin 9 (PCSK9) has recently emerged as a new, promising key therapeutic target for hypercholesterolemia. PCSK9 is a protease involved in chaperoning the low-density lipoprotein receptor to the process of degradation. PCSK9 inhibitors and statins effectively lower LDL-C. The PCSK9 inhibitors decrease the degradation of the LDL receptors, whereas statins mainly interfere with the synthetic machinery of cholesterol by inhibiting the key rate limiting enzyme, the HMG CoA reductase. PCSK9 inhibitors are currently being developed as monoclonal antibodies for their primary use in lowering LDL-C. They may be especially useful for patients with homozygous familial hypercholesterolemia, who at present receive minimal benefit from traditional statin therapy. The monoclonal antibody PCSK9 inhibitors, recently granted FDA approval, show the most promising safety and efficacy profile compared to other, newer LDL-C lowering therapies. This review will primarily focus on the safety and efficacy of monoclonal antibody PCSK9 inhibitors in comparison to statins. The review will also address new, alternative PCSK9 targeting drug classes such as small molecules, gene silencing agents, apolipoprotein B antisense oligonucleotides, and microsomal triglyceride transfer protein inhibitors. PMID:27133571

  13. A robust method for handling low density regions in hybrid simulations for collisionless plasmas

    SciTech Connect

    Amano, Takanobu Higashimori, Katsuaki; Shirakawa, Keisuke

    2014-10-15

    A robust method to handle vacuum and near vacuum regions in hybrid simulations for space and astrophysical plasmas is presented. The conventional hybrid simulation model dealing with kinetic ions and a massless charge-neutralizing electron fluid is known to be susceptible to numerical instability due to divergence of the whistler-mode wave dispersion, as well as division-by-density operation in regions of low density. Consequently, a pure vacuum region is not allowed to exist in the simulation domain unless some ad hoc technique is used. To resolve this difficulty, an alternative way to introduce finite electron inertia effect is proposed. Contrary to the conventional method, the proposed one introduces a correction to the electric field rather than the magnetic field. It is shown that the generalized Ohm's law correctly reduces to Laplace's equation in a vacuum which therefore does not involve any numerical problems. In addition, a variable ion-to-electron mass ratio is introduced to reduce the phase velocity of high frequency whistler waves at low density regions so that the stability condition is always satisfied. It is demonstrated that the proposed model is able to handle near vacuum regions generated as a result of nonlinear self-consistent development of the system, as well as pure vacuum regions set up at the initial condition, without losing the advantages of the standard hybrid code.

  14. Uptake and processing of remnants of chylomicrons and very low density lipoproteins by rat liver

    SciTech Connect

    Jones, A.L.; Hradek, G.T.; Hornick, C.; Renaud, G.; Windler, E.E.; Havel, R.J.

    1984-11-01

    In the rat, chylomicron remnants and very low density lipoprotein (VLDL) remnants are taken up into the liver by high affinity processes and appear to undergo degradation by lysosomes. The relationship of this catabolic process to the known pathways of uptake and degradation of low density lipoproteins (LDL) and the involvement of nonparenchymal cells are addressed in these studies. The authors have utilized both light and electron microscopic radioautography to determine whether the pathway of intracellular transport and catabolism resembles that established for LDL in hepatocytes. Radioiodinated plasma VLDL remnants and lymph chylomicron remnants were injected into femoral veins of rats and the livers were fixed by perfusion 3 to 30 minutes later. Quantitative light microscopic radioautography showed little or no accumulation of grains over Kupffer cells. Electromicroscopic radioautography confirmed these observations and, in addition, demonstrated that very few grains were associated with endothelial cells. The processing of the remnant particles closely resembled that of LDL. Following an initial association of grains with the parenchymal cell plasma membrane, frequently in regions in close proximity to clathrin-coated endocytic pits, the grains were found in endocytic vesicles just beneath the plasma membrane. By 15 minutes the grains were found over multivesicular bodies located in the Golgi-lysosome region of the cell. Thirty minutes after injection, radioautographic grains began to be associated with secondary lysosomes.

  15. DSMC Simulation and Experimental Validation of Shock Interaction in Hypersonic Low Density Flow

    PubMed Central

    2014-01-01

    Direct simulation Monte Carlo (DSMC) of shock interaction in hypersonic low density flow is developed. Three collision molecular models, including hard sphere (HS), variable hard sphere (VHS), and variable soft sphere (VSS), are employed in the DSMC study. The simulations of double-cone and Edney's type IV hypersonic shock interactions in low density flow are performed. Comparisons between DSMC and experimental data are conducted. Investigation of the double-cone hypersonic flow shows that three collision molecular models can predict the trend of pressure coefficient and the Stanton number. HS model shows the best agreement between DSMC simulation and experiment among three collision molecular models. Also, it shows that the agreement between DSMC and experiment is generally good for HS and VHS models in Edney's type IV shock interaction. However, it fails in the VSS model. Both double-cone and Edney's type IV shock interaction simulations show that the DSMC errors depend on the Knudsen number and the models employed for intermolecular interaction. With the increase in the Knudsen number, the DSMC error is decreased. The error is the smallest in HS compared with those in the VHS and VSS models. When the Knudsen number is in the level of 10−4, the DSMC errors, for pressure coefficient, the Stanton number, and the scale of interaction region, are controlled within 10%. PMID:24672360

  16. DSMC simulation and experimental validation of shock interaction in hypersonic low density flow.

    PubMed

    Xiao, Hong; Shang, Yuhe; Wu, Di

    2014-01-01

    Direct simulation Monte Carlo (DSMC) of shock interaction in hypersonic low density flow is developed. Three collision molecular models, including hard sphere (HS), variable hard sphere (VHS), and variable soft sphere (VSS), are employed in the DSMC study. The simulations of double-cone and Edney's type IV hypersonic shock interactions in low density flow are performed. Comparisons between DSMC and experimental data are conducted. Investigation of the double-cone hypersonic flow shows that three collision molecular models can predict the trend of pressure coefficient and the Stanton number. HS model shows the best agreement between DSMC simulation and experiment among three collision molecular models. Also, it shows that the agreement between DSMC and experiment is generally good for HS and VHS models in Edney's type IV shock interaction. However, it fails in the VSS model. Both double-cone and Edney's type IV shock interaction simulations show that the DSMC errors depend on the Knudsen number and the models employed for intermolecular interaction. With the increase in the Knudsen number, the DSMC error is decreased. The error is the smallest in HS compared with those in the VHS and VSS models. When the Knudsen number is in the level of 10(-4), the DSMC errors, for pressure coefficient, the Stanton number, and the scale of interaction region, are controlled within 10%.

  17. Shock Initiation Experiments with Ignition and Growth Modeling on Low Density Composition B

    NASA Astrophysics Data System (ADS)

    Vandersall, Kevin S.; Garcia, Frank; Tarver, Craig M.

    2015-06-01

    Shock initiation experiments on low density (~1.2 and ~1.5 g/cm3) Composition B were performed to obtain in-situ pressure gauge data, characterize the run-distance-to-detonation behavior, and provide a basis for Ignition and Growth reactive flow modeling. A 101 mm diameter gas gun was utilized to initiate the explosive charges with manganin piezoresistive pressure gauge packages placed between packed layers (~1.2 g/cm3) confined in Teflon rings or sample disks pressed to low density (~1.5 g/cm3) . The shock sensitivity was found to increase with decreasing density as expected. Ignition and Growth model parameters were derived that yielded reasonable agreement with the experimental data at both initial densities. The shock sensitivity at the tested densities will be compared to prior work published as near full density material. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. This work was funded in part by the Joint DoD-DOE Munitions Program.

  18. Comparison of High and Low Density Airborne LIDAR Data for Forest Road Quality Assessment

    NASA Astrophysics Data System (ADS)

    Kiss, K.; Malinen, J.; Tokola, T.

    2016-06-01

    Good quality forest roads are important for forest management. Airborne laser scanning data can help create automatized road quality detection, thus avoiding field visits. Two different pulse density datasets have been used to assess road quality: high-density airborne laser scanning data from Kiihtelysvaara and low-density data from Tuusniemi, Finland. The field inventory mainly focused on the surface wear condition, structural condition, flatness, road side vegetation and drying of the road. Observations were divided into poor, satisfactory and good categories based on the current Finnish quality standards used for forest roads. Digital Elevation Models were derived from the laser point cloud, and indices were calculated to determine road quality. The calculated indices assessed the topographic differences on the road surface and road sides. The topographic position index works well in flat terrain only, while the standardized elevation index described the road surface better if the differences are bigger. Both indices require at least a 1 metre resolution. High-density data is necessary for analysis of the road surface, and the indices relate mostly to the surface wear and flatness. The classification was more precise (31-92%) than on low-density data (25-40%). However, ditch detection and classification can be carried out using the sparse dataset as well (with a success rate of 69%). The use of airborne laser scanning data can provide quality information on forest roads.

  19. Effects of low-density feeding on elk–fetus contact rates on Wyoming feedgrounds

    USGS Publications Warehouse

    Creech, Tyler G.; Cross, Paul C.; Scurlock, Brandon M.; Maichak, Eric J.; Rogerson, Jared D.; Henningsen, John C.; Creel, Scott

    2012-01-01

    High seroprevalance for Brucella abortus among elk on Wyoming feedgrounds suggests that supplemental feeding may influence parasite transmission and disease dynamics by altering the rate at which elk contact infectious materials in their environment. We used proximity loggers and video cameras to estimate rates of elk-to-fetus contact (the primary source of brucellosis transmission) during winter supplemental feeding. We compared contact rates during high-density and low-density (LD) feeding treatments that provided the same total amount of food distributed over different areas. Low-density feeding led to >70% reductions in total number of contacts and number of individuals contacting a fetus. Proximity loggers and video cameras provided similar estimates of elk–fetus contact rates. Elk contacted fetuses and random control points equally, suggesting that elk were not attracted to fetuses but encountered them incidentally while feeding. The modeled relationship between contact rate and disease prevalence is nonlinear and LD feeding may result in large reductions in brucellosis prevalence, but this depends on the amount of transmission that occurs on and off feedgrounds.

  20. Preferential enrichment of large-sized very low density lipoprotein populations with transferred cholesteryl esters

    SciTech Connect

    Eisenberg, S.

    1985-04-01

    The effect of lipid transfer proteins on the exchange and transfer of cholesteryl esters from rat plasma HDL2 to human very low (VLDL) and low density (LDL) lipoprotein populations was studied. The use of a combination of radiochemical and chemical methods allowed separate assessment of (/sup 3/H)cholesteryl ester exchange and of cholesteryl ester transfer. VLDL-I was the preferred acceptor for transferred cholesteryl esters, followed by VLDL-II and VLDL-III. LDL did not acquire cholesteryl esters. The contribution of exchange of (/sup 3/H)cholesteryl esters to total transfer was highest for LDL and decreased in reverse order along the VLDL density range. Inactivation of lecithin: cholesterol acyltransferase (LCAT) and heating the HDL2 for 60 min at 56 degrees C accelerated transfer and exchange of (/sup 3/H)cholesteryl esters. Addition of lipid transfer proteins increased cholesterol esterification in all systems. The data demonstrate that large-sized, triglyceride-rich VLDL particles are preferred acceptors for transferred cholesteryl esters. It is suggested that enrichment of very low density lipoproteins with cholesteryl esters reflects the triglyceride content of the particles.

  1. Lowering low-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus

    PubMed Central

    Bays, Harold E

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of β-cell function. T2DM patients are at increased risk of micro- and macrovascular disease, and are often considered as representing an atherosclerotic coronary heart disease (CHD) risk equivalent. Interventions directed at glucose and lipid level control in T2DM patients may reduce micro- and macrovascular disease. The optimal T2DM agent is one that lowers glucose levels with limited risk for hypoglycemia, and with no clinical trial evidence of worsening CHD risk. Lipid-altering drugs should preferably reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have evidence that the mechanism of action reduces CHD risk. Statins reduce low-density lipoprotein cholesterol and apo B and have evidence of improving CHD outcomes, and are thus first-line therapy for the treatment of hypercholesterolemia. In patients who do not achieve optimal lipid levels with statin therapy, or who are intolerant to statin therapy, add-on therapy or alternative therapies may be indicated. Additional available agents to treat hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates, niacin, and ezetimibe. This review discusses the use of these alternative agents to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in combination with statin therapy. PMID:25045281

  2. Multiple unit gastroretentive drug delivery systems: a new preparation method for low density microparticles.

    PubMed

    Streubel, A; Siepmann, J; Bodmeier, R

    2003-01-01

    The aim of this study was to develop a new preparation method for low density foam-based, floating microparticles and to demonstrate the systems' performance in vitro. Major advantages of the novel preparation technique include: (i) short processing times, (ii) no exposure of the ingredients to high temperatures, (iii) the possibility to avoid toxic organic solvents, and (iv) high encapsulation efficiencies close to 100%. Floating microparticles consisting of polypropylene foam powder, model drug [chlorpheniramine maleate (CPM), diltiazem HCl, theophylline or verapamil HCl] and polymer [Eudragit RS or polymethyl methacrylate (PMMA)] were prepared by soaking the microporous foam carrier with an organic solution of drug and polymer and subsequent drying. The effects of various formulation and processing parameters on the resulting in vitro floating behaviour, internal and external particle morphology, drug loading, in vitro drug release and physical state of the incorporated drug were studied. Good in vitro floating behaviour was observed in most cases and a broad variety of drug release patterns could be achieved by varying the drug loading and type of polymer. Interestingly, PMMA-based microparticles showed incomplete drug release with verapamil HCl. This restriction could be overcome by forming the free base of the drug prior to microparticle preparation. In contrast to the salt, the free base acted as a plasticizer for PMMA, resulting in sufficiently high diffusion coefficients and, consequently, complete drug release. The low density microparticles were compressed into rapidly disintegrating tablets in order to provide an administrable oral dosage form.

  3. A microfluidic device for the automated electrical readout of low-density glass-slide microarrays.

    PubMed

    Díaz-González, María; Salvador, J Pablo; Bonilla, Diana; Marco, M Pilar; Fernández-Sánchez, César; Baldi, Antoni

    2015-12-15

    Microarrays are a powerful platform for rapid and multiplexed analysis in a wide range of research fields. Electrical readout systems have emerged as an alternative to conventional optical methods for microarray analysis thanks to its potential advantages like low-cost, low-power and easy miniaturization of the required instrumentation. In this work an automated electrical readout system for low-cost glass-slide microarrays is described. The system enables the simultaneous conductimetric detection of up to 36 biorecognition events by incorporating an array of interdigitated electrode transducers. A polydimethylsiloxane microfluidic structure has been designed that creates microwells over the transducers and incorporates the microfluidic channels required for filling and draining them with readout and cleaning solutions, thus making the readout process fully automated. Since the capture biomolecules are not immobilized on the transducer surface this readout system is reusable, in contrast to previously reported electrochemical microarrays. A low-density microarray based on a competitive enzymatic immunoassay for atrazine detection was used to test the performance of the readout system. The electrical assay shows a detection limit of 0.22±0.03 μg L(-1) similar to that obtained with fluorescent detection and allows the direct determination of the pesticide in polluted water samples. These results proved that an electrical readout system such as the one presented in this work is a reliable and cost-effective alternative to fluorescence scanners for the analysis of low-density microarrays.

  4. Application of adaptive cluster sampling to low-density populations of freshwater mussels

    USGS Publications Warehouse

    Smith, D.R.; Villella, R.F.; Lemarie, D.P.

    2003-01-01

    Freshwater mussels appear to be promising candidates for adaptive cluster sampling because they are benthic macroinvertebrates that cluster spatially and are frequently found at low densities. We applied adaptive cluster sampling to estimate density of freshwater mussels at 24 sites along the Cacapon River, WV, where a preliminary timed search indicated that mussels were present at low density. Adaptive cluster sampling increased yield of individual mussels and detection of uncommon species; however, it did not improve precision of density estimates. Because finding uncommon species, collecting individuals of those species, and estimating their densities are important conservation activities, additional research is warranted on application of adaptive cluster sampling to freshwater mussels. However, at this time we do not recommend routine application of adaptive cluster sampling to freshwater mussel populations. The ultimate, and currently unanswered, question is how to tell when adaptive cluster sampling should be used, i.e., when is a population sufficiently rare and clustered for adaptive cluster sampling to be efficient and practical? A cost-effective procedure needs to be developed to identify biological populations for which adaptive cluster sampling is appropriate.

  5. Analysis of Compaction Shock Interactions During DDT of Low Density HMX

    NASA Astrophysics Data System (ADS)

    Rao, Pratap; Gonthier, Keith

    2015-06-01

    Deflagration-to-Detonation Transition (DDT) within low density HMX often occurs by a complex mechanism that involves compaction shock interactions. Piston driven DDT experiments indicate that detonation can be abruptly triggered by the interaction of a strong combustion driven shock and a lead piston supported shock, where the nature of the interaction depends on initial density and lead shock strength. These shocks induce dissipation and thermomechanical fluctuations at the meso-scale due to pore collapse resulting in hot-spots. Inert meso-scale simulations of successive shock loading of low density HMX are performed to examine how dissipation and hot-spot formation are affected by initial density, and lead and trailing shock strength. Emphasis is placed on interpreting solutions in a phase space expressed in terms of effective pressure and dissipative work because of their relevance to hot-spot formation. Meso-scale predictions are shown to compare favorably to those given by a macro-scale theory. This information is being used to formulate a dissipation-dependent reactive burn model to describe shock desensitization and DDT. Preliminary redictions will be presented that illustrate how initial density and input shock strength can affect the transition mechanism. This research is supported by the Defense Threat Reduction Agency (DTRA) under sponsor Award Number HDTRA1-10-1-0018, and the Air Force Research Laboratory (AFRL-RWME) under sponsor Award Number FA8651-09-0021.

  6. Uniform electron gases. III. Low-density gases on three-dimensional spheres

    SciTech Connect

    Agboola, Davids; Knol, Anneke L.; Gill, Peter M. W. Loos, Pierre-François

    2015-08-28

    By combining variational Monte Carlo (VMC) and complete-basis-set limit Hartree-Fock (HF) calculations, we have obtained near-exact correlation energies for low-density same-spin electrons on a three-dimensional sphere (3-sphere), i.e., the surface of a four-dimensional ball. In the VMC calculations, we compare the efficacies of two types of one-electron basis functions for these strongly correlated systems and analyze the energy convergence with respect to the quality of the Jastrow factor. The HF calculations employ spherical Gaussian functions (SGFs) which are the curved-space analogs of Cartesian Gaussian functions. At low densities, the electrons become relatively localized into Wigner crystals, and the natural SGF centers are found by solving the Thomson problem (i.e., the minimum-energy arrangement of n point charges) on the 3-sphere for various values of n. We have found 11 special values of n whose Thomson sites are equivalent. Three of these are the vertices of four-dimensional Platonic solids — the hyper-tetrahedron (n = 5), the hyper-octahedron (n = 8), and the 24-cell (n = 24) — and a fourth is a highly symmetric structure (n = 13) which has not previously been reported. By calculating the harmonic frequencies of the electrons around their equilibrium positions, we also find the first-order vibrational corrections to the Thomson energy.

  7. DSMC simulation and experimental validation of shock interaction in hypersonic low density flow.

    PubMed

    Xiao, Hong; Shang, Yuhe; Wu, Di

    2014-01-01

    Direct simulation Monte Carlo (DSMC) of shock interaction in hypersonic low density flow is developed. Three collision molecular models, including hard sphere (HS), variable hard sphere (VHS), and variable soft sphere (VSS), are employed in the DSMC study. The simulations of double-cone and Edney's type IV hypersonic shock interactions in low density flow are performed. Comparisons between DSMC and experimental data are conducted. Investigation of the double-cone hypersonic flow shows that three collision molecular models can predict the trend of pressure coefficient and the Stanton number. HS model shows the best agreement between DSMC simulation and experiment among three collision molecular models. Also, it shows that the agreement between DSMC and experiment is generally good for HS and VHS models in Edney's type IV shock interaction. However, it fails in the VSS model. Both double-cone and Edney's type IV shock interaction simulations show that the DSMC errors depend on the Knudsen number and the models employed for intermolecular interaction. With the increase in the Knudsen number, the DSMC error is decreased. The error is the smallest in HS compared with those in the VHS and VSS models. When the Knudsen number is in the level of 10(-4), the DSMC errors, for pressure coefficient, the Stanton number, and the scale of interaction region, are controlled within 10%. PMID:24672360

  8. On the feasibility of increasing the energy of laser-accelerated protons by using low-density targets

    SciTech Connect

    Brantov, A. V. Bychenkov, V. Yu.

    2015-06-15

    Optimal regimes of proton acceleration in the interaction of short high-power laser pulses with thin foils and low-density targets are determined by means of 3D numerical simulation. It is demonstrated that the maximum proton energy can be increased by using low-density targets in which ions from the front surface of the target are accelerated most efficiently. It is shown using a particular example that, for the same laser pulse, the energy of protons accelerated from a low-density target can be increased by one-third as compared to a solid-state target.

  9. Crystallization and morphologies of linear low density polyethylene and its blends with high density polyethylene

    NASA Astrophysics Data System (ADS)

    Bischel, Marsha Stalker

    Knowledge of the kinetics of polymer crystallization is important in controlling polymer forming processes, while knowledge of the resulting microstructure is important in predicting the ultimate mechanical properties of the material. It is also known that processing parameters will affect the ultimate morphology and properties of the sample. The crystallization, morphology and mechanical properties of a specific linear low density polyethylene copolymer and its blends with two high density polyethylene homopolymers of differing molecular weight are investigated. Several new techniques are employed in an effort to examine the effect of crystallization kinetics on the development of morphology. These include the simultaneous processing of thin film and bulk samples, and the use of atomic force microscopy to generate images of the microstructure. Thermal properties, and melting and crystallization behaviors are examined with differential scanning calorimetry. The mechanical properties of the blends, as a function of crystallization temperature and blend content, are examined through the use of microhardness testing, and nanoindentation testing via the atomic force microscope. The former provides hardness values, which are related to both the elastic moduli and yield strengths of the samples; the latter technique provides a new method for deriving the relative elastic moduli of the component polymers, as well as for specific structures within the morphology. This provides a novel means of determining the distribution of the component polymers within the blend. The rates of crystallization for the blends and the component polymers are analyzed with respect to the Hoffman Kinetic Theory for the crystallization of polymers to determine whether the existing theory is adequate for describing the behaviors of the blends. It has been determined that the blend systems form a co-crystalline microstructure; however, significant amounts of linear low density polyethylene are

  10. Scavenger receptor-independent stimulation of cholesterol esterification in macrophages by low density lipoprotein extracted from human aortic intima.

    PubMed

    Steinbrecher, U P; Lougheed, M

    1992-05-01

    There is a growing body of evidence that suggests that modification of low density lipoprotein (LDL) in the artery wall may contribute to atherogenesis. A number of physiologically plausible modifications have been studied in vitro, including oxidation, aggregation, formation of complexes with glycosaminoglycans, and generation of LDL-immune complexes. Several studies of the properties of LDL extracted from the aortic intima have been published, but these indicate disagreement about both the nature and the extent of modification of LDL in the artery wall. The objectives of the present study were to determine the nature and extent of modification of LDL extracted from both normal and diseased human aortic intimas and to correlate this with the rate of LDL uptake in cultured cells. Analyses were performed on LDLs isolated from aortic intimas obtained at autopsy or at the time of organ harvest from 33 subjects. LDL from normal intima showed no clear evidence of oxidation but had slightly increased electrophoretic mobility compared with native plasma LDL, whereas LDL from plaques or fatty streaks exhibited variable but usually modest signs of oxidative change. Aortic LDL was more rapidly degraded by cultured macrophages than was plasma LDL and resulted in a greater stimulation of cholesterol esterification. The degree of stimulation of cholesterol esterification was correlated with the extent of modification of LDL as reflected by the degree of apolipoprotein B fragmentation. However, in all aortic LDLs the extent of oxidative change, as assessed by electrophoretic mobility or other physical parameters, was less than that required for scavenger receptor-mediated uptake. In all cases where sufficient amounts of LDL were recovered to permit degradation experiments, the uptake of aortic LDL was nonsaturable and could not be inhibited by polyinosinic acid or acetylated LDL. Chromatography on Sepharose CL-4B showed that most LDLs isolated from plaque contained a fraction

  11. [Composition and metabolism of extremely low-density lipoproteins in normal rabbits of different age and under experimental atherosclerosis].

    PubMed

    Chaialo, P P

    1981-01-01

    The lipid composition and protein content in extremely low-density lipoproteids. lipoproteid-lypase activity and breakdown dynamics of the mentioned [3H]cholesterol-labelled lipoproteids are studied in blood of young and old rabbits in norm and under experimental atherosclerosis. It is shown that in normal animals the content of all lipid components and protein decreases with ageing in the fraction of extremely low-density lipoproteids isolated from blood serum. The activity of lipoproteid lypase and breakdown of intravenously injected labelled extremely low-density lipoproteids are lowered in old animals as well. Under experimental atherosclerosis in extremely low-density lipoproteids there occurs accumulation of cholesterol esters in considerable amounts, the breakdown of the class lipoproteids is slown down. The enzymic activity manifests no significant changes in comparison with the norm. Disturbances in the composition of lipoproteids and their metabolism with the studied pathology are more pronounced in old rabbits than in young ones.

  12. The thermal and mechanical properties of a low density elastomeric ablation material

    NASA Technical Reports Server (NTRS)

    Engelke, W. T.; Robertson, R. W.; Bush, A. L.; Pears, C. D.

    1973-01-01

    Thermal and mechanical properties data were obtained for a low density elastomeric resin based ablation material with phenolic-glass honeycomb reinforcement. Data were obtained for the material in the charred and uncharred state. Ablation material specimens were charred in a laboratory furnace at temperatures in the range from 600 K to 1700 K to obtain char specimens representative of the ablation char layer formed during reentry. These specimens were then used to obtain effective thermal conductivity, heat capacity, porosity, and permeability data at the char formation temperature. This provided a boxing of the data which enables the prediction of the transient response of the material during ablation. Limited comparisons were made between the furnace charred specimens and specimens which had been exposed to simulated reentry conditions.

  13. Fracture toughness/Young's modulus correlation for low-density fibrous silica bodies

    NASA Technical Reports Server (NTRS)

    Green, D. J.

    1983-01-01

    Fracture toughness and static Young's modulus were measured for the low-density silic fiber materials used as tiles in the thermal protection system of the Space Shuttle. The fracture behavior was found to be in excellent agreement with a previously formulated micromechanical model and allowed both (density) classes of tile material to be correlated to a single function. A similar correlation was also found between strength and Young's modulus, which is the basis of a nondestructive evaluation test for these materials. It was shown that the value of Young's modulus determined from a dynamic test can be substantially greater than that determined in a static mechanical test. This effect must be taken into account in the correlation. Finally, it was also determined that these materials have significant variations in Kc, both within and between production units, so that the strength variability in these materials is dependent on both fracture toughness and flaw-size variations.

  14. Improvement of impact strength in linear low density polyethylene (LLDPE) by blending with amorphous polymers

    SciTech Connect

    Mirabella, F.M. Jr.

    1996-12-31

    The objective of the current work was to improve the film impact strength of commercial linear low density polyethylene (LLDPE) resins, while maintaining or improving other desirable properties. The approach used was to blend rubber-like (i.e. essentially noncrystalline) polymer resins with the base resin LLDPE. The choice of the rubber-like components was largely dictated by their commercial availability. The rubber-like polymers chosen were poly (ethylene-vinyl acetate) [EVA], poly (ethylene-n-butyl acrylate) [EnBA], and poly (ethylene-propylene) rubber [EPR]. The weight percent range of addition of the rubber-like component was restricted to 5% - 20%. The preferred range was only up to 10%. The structure of the base LLDPE resin, rubber-like components and the blends thereof was characterized. The physical and mechanical properties of the blown films of the resin blends were measured and correlations between structure and properties were determined.

  15. Cryogenic mechanical properties of low density superplastically formable Al-Li alloys

    SciTech Connect

    Verzasconi, S.L.; Morris, J.W. Jr.

    1989-03-01

    The aerospace industry is considering the use of low density, superplastically formable (SPF) materials, such as Al-Li alloys in cryogenic tankage. SPF modifications of alloys 8090, 2090, and 2090 + In were tested for strength and Kahn tear toughness. The results were compared to those of similar tests of 2219-T87, an alloy currently used in cryogenic tankage, and 2090-T81, a recently studied Al-Li alloy with exceptional cryogenic properties. With decreasing temperature, all materials showed an increase in strength, while most materials showed an increase in elongation and decrease in Kahn toughness. The indium addition to 2090 increased alloy strength, but did not improve the strength-toughness combination. The fracture mode was predominantly intergranular along small, recrystallized grains, with some transgranular fracture, some ductile rupture, and some delamination on large, unrecrystallized grains. 17 refs., 3 figs., 3 tabs.

  16. Low-density carbonized composite foams for direct-drive laser ICF targets

    SciTech Connect

    Kong, Fung-Ming

    1989-03-01

    The design for a direct-drive, high-gain laser inertial confinement fusion target calls for the use of a low-density, low-atomic-number foam to confine and stabilize liquid deuterium-tritium (DT) in a spherical-shell configuration. Over the past two years, we have successfully developed polystyrene foams (PS) and carbonized resorcinol-formaldehyde foams (CRF) for that purpose. Both candidates are promising materials with unique characteristics. PS has superior mechanical strength and machinability, but its relatively large thermal contraction is a significant disadvantage. CRF has outstanding wettability and dimensional stability in liquid DT; yet it is much more fragile than PS. To combine the strengths of both materials, we have recently developed a polymer composite foam which exceeds PS in mechanical strength, but retains the wettability and dimension stability of CRF. This paper will discuss the preparation, structure, and properties of the polymer composite foams. 5 refs., 1 fig., 1 tab.

  17. Ultra Low Density Shape Memory Polymer Foams With Tunable Physicochemical Properties for Treatment of intracranial Aneurysms

    SciTech Connect

    Singhal, Pooja

    2013-12-01

    Shape memory polymers (SMPs) are a rapidly emerging class of smart materials that can be stored in a deformed temporary shape, and can actively return to their original shape upon application of an external stimulus such as heat, pH or light. This behavior is particularly advantageous for minimally invasive biomedical applications comprising embolic/regenerative scaffolds, as it enables a transcatheter delivery of the device to the target site. The focus of this work was to exploit this shape memory behavior of polyurethanes, and develop an efficient embolic SMP foam device for the treatment of intracranial aneurysms.In summary, this work reports a novel family of ultra low density polymer foams which can be delivered via a minimally invasive surgery to the aneurysm site, actuated in a controlled manner to efficiently embolize the aneurysm while promoting physiological fluid/blood flow through the reticulated/open porous structure, and eventually biodegrade leading to complete healing of the vasculature.

  18. Mechanical properties of low-density polyethylene filled by graphite nanoplatelets.

    PubMed

    Carotenuto, G; De Nicola, S; Palomba, M; Pullini, D; Horsewell, A; Hansen, T W; Nicolais, L

    2012-12-01

    The mechanical properties of GNP/LDPE nanocomposites (graphite nanoplatelets/low density polyethylene) have been investigated, in order to establish the effect of nanoscale reinforcement within the polymer matrix. Results show that the presence of the filler does not involve a change in the microscopic structure of the polymer. However, on a macroscopic scale, GNPs limit the mobility of the polymer chains, resulting in an increase in stiffness for the final composite. Orientation of GNPs within the LDPE matrix is also an important issue that affects mechanical properties and it has been evaluated by testing nanocomposites made by different manufacturing techniques (compression moulding and blown extrusion). The comparison between the experimental data and the Halpin-Tsai model shows that the orientation of GNPs due to the extrusion process leads to values of tensile modulus higher than that obtained with the randomly oriented disposition resulting from the compression moulding technique. PMID:23128320

  19. Low density microcellular carbon or catalytically impregnated carbon forms and process for their preparation

    DOEpatents

    Hopper, Robert W.; Pekala, Richard W.

    1989-01-01

    Machinable and structurally stable, low density microcellular carbon, and catalytically impregnated carbon, foams, and process for their preparation, are provided. Pulverized sodium chloride is classified to improve particle size uniformity, and the classified particles may be further mixed with a catalyst material. The particles are cold pressed into a compact having internal pores, and then sintered. The sintered compact is immersed and then submerged in a phenolic polymer solution to uniformly fill the pores of the compact with phenolic polymer. The compact is then heated to pyrolyze the phenolic polymer into carbon in the form of a foam. Then the sodium chloride of the compact is leached away with water, and the remaining product is freeze dried to provide the carbon, or catalytically impregnated carbon, foam.

  20. Low density microcellular carbon or catalytically impregnated carbon foams and process for their preparation

    DOEpatents

    Hooper, R.W.; Pekala, R.W.

    1987-04-30

    Machinable and structurally stable, low density microcellular carbon, and catalytically impregnated carbon, foams, and process for their preparation, are provided. Pulverized sodium chloride is classified to improve particle size uniformity, and the classified particles may be further mixed with a catalyst material. The particles are cold pressed into a compact having internal pores, and then sintered. The sintered compact is immersed and then submerged in a phenolic polymer solution to uniformly fill the pores of the compact with phenolic polymer. The compact is then heated to pyrolyze the phenolic polymer into carbon in the form of a foam. Then the sodium chloride of the compact is leached away with water, and the remaining product is freeze dried to provide the carbon, or catalytically impregnated carbon, foam.

  1. Low density microcellular carbon or catalytically impregnated carbon foams and process for their prepartion

    DOEpatents

    Hopper, Robert W.; Pekala, Richard W.

    1988-01-01

    Machinable and structurally stable, low density microcellular carbon, and catalytically impregnated carbon, foams, and process for their preparation, are provided. Pulverized sodium chloride is classified to improve particle size uniformity, and the classified particles may be further mixed with a catalyst material. The particles are cold pressed into a compact having internal pores, and then sintered. The sintered compact is immersed and then submerged in a phenolic polymer solution to uniformly fill the pores of the compact with phenolic polymer. The compact is then heated to pyrolyze the phenolic polymer into carbon in the form of a foam. Then the sodium chloride of the compact is leached away with water, and the remaining product is freeze dried to provide the carbon, or catalytically impregnated carbon, foam.

  2. Structure and Dynamics of Low-Density and High-Density Liquid Water at High Pressure.

    PubMed

    Fanetti, Samuele; Lapini, Andrea; Pagliai, Marco; Citroni, Margherita; Di Donato, Mariangela; Scandolo, Sandro; Righini, Roberto; Bini, Roberto

    2014-01-01

    Liquid water has a primary role in ruling life on Earth in a wide temperature and pressure range as well as a plethora of chemical, physical, geological, and environmental processes. Nevertheless, a full understanding of its dynamical and structural properties is still lacking. Water molecules are associated through hydrogen bonds, with the resulting extended network characterized by a local tetrahedral arrangement. Two different local structures of the liquid, called low-density (LDW) and high-density (HDW) water, have been identified to potentially affect many different chemical, biological, and physical processes. By combining diamond anvil cell technology, ultrafast pump-probe infrared spectroscopy, and classical molecular dynamics simulations, we show that the liquid structure and orientational dynamics are intimately connected, identifying the P-T range of the LDW and HDW regimes. The latter are defined in terms of the speeding up of the orientational dynamics, caused by the increasing probability of breaking and reforming the hydrogen bonds.

  3. High-Tc superconductor/linear low density polyethylene (LLDPE) composite materials for diamagnetic applications

    NASA Astrophysics Data System (ADS)

    Bhadrakumari, S.; Predeep, P.

    2006-08-01

    A series of composite samples of YBa2Cu3O7-x and linear low density polyethylene (Y-123/LLDPE) with volume percentage ranging from 0 to 75% was prepared. The crystallinity of the composites was studied using x-ray diffraction (XRD) patterns. It is found that the percentage of crystallinity in the composite samples increases with increasing volume of the LLDPE. A four-phase system for the composite materials may be inferred from a combination of XRD and density data. Repulsive force measurements showed that the diamagnetic properties were preserved in the composites and the samples exhibited appreciable magnetic levitation forces and this force increases with increasing volume fraction of the superconductor filler.

  4. Low-density resin impregnated ceramic article and method for making the same

    NASA Technical Reports Server (NTRS)

    Tran, Huy K. (Inventor); Henline, William D. (Inventor); Hsu, Ming-ta S. (Inventor); Rasky, Daniel J. (Inventor); Riccitiello, Salvatore R. (Inventor)

    1997-01-01

    A low-density resin impregnated ceramic article advantageously employed as a structural ceramic ablator comprising a matrix of ceramic fibers. The fibers of the ceramic matrix are coated with an organic resin film. The organic resin can be a thermoplastic resin or a cured thermosetting resin. In one embodiment, the resin is uniformly distributed within the ceramic article. In a second embodiment, the resin is distributed so as to provide a density gradient along at least one direction of the ceramic article. The resin impregnated ceramic article is prepared by providing a matrix of ceramic fibers; immersing the matrix of ceramic fibers in a solution of a solvent and an organic resin infiltrant; and removing the solvent to form a resin film on the ceramic fibers.

  5. Reticulation of low density shape memory polymer foam with an in vivo demonstration of vascular occlusion

    DOE PAGESBeta

    Rodriguez, Jennifer N.; Miller, Matthew W.; Boyle, Anthony; Horn, John; Yang, Cheng-Kang; Wilson, Thomas S.; Ortega, Jason M.; Small, Ward; Nash, Landon; Skoog, Hunter; et al

    2014-08-11

    Recently, predominantly closed-cell low density shape memory polymer (SMP) foam was reported to be an effective aneurysm filling device in a porcine model (Rodriguez et al., Journal of Biomedical Materials Research Part A 2013: (http://dx.doi.org/10.1002/jbm.a.34782)). Because healing involves blood clotting and cell migration throughout the foam volume, a more open-cell structure may further enhance the healing response. This research sought to develop a non-destructive reticulation process for this SMP foam to disrupt the membranes between pore cells. Non-destructive mechanical reticulation was achieved using a gravity-driven floating nitinol pin array coupled with vibratory agitation of the foam and supplemental chemical etching.more » Lastly, reticulation resulted in a reduced elastic modulus and increased permeability, but did not impede the shape memory behavior. Reticulated foams were capable of achieving rapid vascular occlusion in an in vivo porcine model.« less

  6. The use of the tethered satellite system to perform low density aerothermodynamics studies

    NASA Technical Reports Server (NTRS)

    Carlomagno, Giovanni M.; Deluca, Luigi; Siemers, Paul M.; Wood, George M., Jr.

    1988-01-01

    The Tethered Satellite System (TSS) is a cooperative space system development activity of the U.S.A. and Italy. It is comprised of the Tether Satellite (TS) and the deployer. Within TSS, the Shuttle Tethered Aerothermodynamic Research Facility (STARFAC) concept has the potential to provide access to vast portions of the upper atmosphere for atmospheric and aerothermodynamic research. The feasibility and capability of the TSS to operate as a continuous open wind tunnel and to perform low density aerothermodynamic studies are investigated. This is accomplished through a modified version of the TS simulation program (SKYHOOK). The results indicate that STARFAC concept is both feasible and practical. The TS can go below 100 km but, if thrust is used, large velocity variation (delta V) maneuvers and an attitude control are required; if a satellite lift is considered, large tether tension is produced and an attitude control is required.

  7. Improvement of nuclide leaching resistance of paraffin waste form with low density polyethylene.

    PubMed

    Kim, Chang Lak; Park, Joo Wan; Kim, Ju Youl; Chung, Chang Hyun

    2002-01-01

    Low-level liquid borate wastes have been immobilized with paraffin wax using a concentrate waste drying system (CWDS) in Korean nuclear power plants. The possibility for improving chemical durability of paraffin waste form was suggested in this study. A small amount of low density polyethylene (LDPE) was added to increase the leaching resistance of the existing paraffin waste form. The influence of LDPE on the leaching behavior of waste form was investigated by performing leaching test according to ANSI/ANS-16.1 procedure during 325 days. It was observed that the leaching of nuclides immobilized within paraffin waste form made a marked reduction although little content of LDPE was added to waste form. The acceptance criteria of paraffin waste form associated with leachability index (LI) and compressive strength after the leaching test were fully satisfied with the help of LDPE.

  8. Density equalisation in supercooled high- and low-density water mixtures

    NASA Astrophysics Data System (ADS)

    English, Niall J.; Kusalik, Peter G.; Tse, John S.

    2013-08-01

    The temporal evolution of two model high-density/low-density (HDL/LDL) interfaces was examined from molecular dynamics (MD) calculations at temperatures close to the predicted second critical point of water for three water models. In all cases, interfacial density equalisation occurred rapidly showing no preference for inhomogenous distribution. A uniform density (of ca. 0.99-1.067 g/cm3, depending on the potential) was always observed at the interface, indicating the free energy of water in low- and high-density forms is metastable, and that LDL and HDL should not coexist as independent entities at thermodynamic equilibrium. It is reckoned that previous MD studies supporting the "two-liquid" model have an explicit, if inappropriate, assumption of mechanical equilibrium between the two phases. The present result challenges the notion that a second critical point exists, and that LDL/HDL mixtures could be even kinetically metastable.

  9. Effect of gamma irradiation on high temperature hardness of low-density polyethylene

    NASA Astrophysics Data System (ADS)

    Chen, Pei-Yun; Yang, Fuqian; Lee, Sanboh

    2015-11-01

    Gamma irradiation can cause the change of microstructure and molecular structure of polymer, resulting in the change of mechanical properties of polymers. Using the hardness measurement, the effect of gamma irradiation on the high temperature hardness of low-density polyethylene (LDPE) was investigated. The gamma irradiation caused the increase in the melting point, the enthalpy of fusion, and the portion of crystallinity of LDPE. The Vickers hardness of the irradiated LDPE increases with increasing the irradiation dose, annealing temperature, and annealing time. The activation energy for the rate process controlling the reaction between defects linearly decreases with the irradiation dose. The process controlling the hardness evolution in LDPE is endothermic because LDPE is semi-crystalline.

  10. Comparison between extensional rheological properties of low density polyethylene melt in SER and RME rheometric systems

    NASA Astrophysics Data System (ADS)

    Narimissa, Esmaeil; Rolón-Garrido, Víctor Hugo; Wagner, Manfred Hermann

    2015-04-01

    Precise evaluation and notional prediction of extensional rheological behaviour of polymeric melts and solutions are of significant importance in polymer industry. This is evident in the well documentation of the dominance of elongational deformation of polymeric systems in processes such as melt spinning, blow moulding, biaxial stretching of extruded sheets, etc. The relevant commercial extensional rheometers thus far discussed in the literature are RME and SER. This research, for the first time, compares the extensional viscosity measurements of low density polyethylene at 140, 150, and 170 °C through RME and SER devices. Despite the observed similarities found in this comparative investigation, the main difference was laid in maximum Hencky strain, strain hardening viscosity, and the variation of those rheological properties with testing temperature of the samples.

  11. Tribological and thermal properties of blends of melamineformaldehyde resins with low density polyethylene

    NASA Astrophysics Data System (ADS)

    Huang, Bernard; Brostow, Witold; Datashvili, Tea

    2006-10-01

    Melamine + formaldehyde resin (MFR) was synthesized and blended with a low density polyethylene (LDPE). Tribological, thermal and morphological properties of LDPE + MFR blends containing 1, 5, 10, 20, 25 wt. % MFR were investigated. After preparing the blends with a Brabender preparation station and a compression molding machine, the following properties were determined: wear rate and friction, sliding wear and microhardness. Thermal properties had been analyzed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). A detailed study on the miscibility behaviour of the blends has been made by using Fourier transform infrared spectroscopy (FTIR), environmental scanning electron microscopy (ESEM) and atomic force microscopy (AFM). The morphological observations are correlated with the properties. Thermal analysis, AFM and ESEM support the presence of a partial compatibilization.

  12. Living Clusters and Crystals from Low-Density Suspensions of Active Colloids

    NASA Astrophysics Data System (ADS)

    Mognetti, B. M.; Šarić, A.; Angioletti-Uberti, S.; Cacciuto, A.; Valeriani, C.; Frenkel, D.

    2013-12-01

    Recent studies aimed at investigating artificial analogs of bacterial colonies have shown that low-density suspensions of self-propelled particles confined in two dimensions can assemble into finite aggregates that merge and split, but have a typical size that remains constant (living clusters). In this Letter, we address the problem of the formation of living clusters and crystals of active particles in three dimensions. We study two systems: self-propelled particles interacting via a generic attractive potential and colloids that can move toward each other as a result of active agents (e.g., by molecular motors). In both cases, fluidlike “living” clusters form. We explain this general feature in terms of the balance between active forces and regression to thermodynamic equilibrium. This balance can be quantified in terms of a dimensionless number that allows us to collapse the observed clustering behavior onto a universal curve. We also discuss how active motion affects the kinetics of crystal formation.

  13. The farnesoid X receptor induces very low density lipoprotein receptor gene expression.

    PubMed

    Sirvent, Audrey; Claudel, Thierry; Martin, Geneviève; Brozek, John; Kosykh, Vladimir; Darteil, Raphaël; Hum, Dean W; Fruchart, Jean-Charles; Staels, Bart

    2004-05-21

    The farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids (BAs). In response to ligand-binding, FXR regulates many genes involved in BA, lipid, and lipoprotein metabolism. To identify new FXR target genes, microarray technology was used to profile total RNA extracted from HepG2 cells treated with the natural FXR agonist chenodeoxycholic acid (CDCA). Interestingly, a significant increase of transcript level of the very low density lipoprotein receptor (VLDLR) was observed. Our data, resulting from selective FXR activation, FXR RNA silencing and FXR-deficient mice, clearly demonstrate that BAs up-regulate VLDLR transcript levels via a FXR-dependent mechanism in vitro in human and in vivo in mouse liver cells.

  14. Reticulation of low density shape memory polymer foam with an in vivo demonstration of vascular occlusion

    SciTech Connect

    Rodriguez, Jennifer N.; Miller, Matthew W.; Boyle, Anthony; Horn, John; Yang, Cheng-Kang; Wilson, Thomas S.; Ortega, Jason M.; Small, Ward; Nash, Landon; Skoog, Hunter; Maitland, Duncan J.

    2014-08-11

    Recently, predominantly closed-cell low density shape memory polymer (SMP) foam was reported to be an effective aneurysm filling device in a porcine model (Rodriguez et al., Journal of Biomedical Materials Research Part A 2013: (http://dx.doi.org/10.1002/jbm.a.34782)). Because healing involves blood clotting and cell migration throughout the foam volume, a more open-cell structure may further enhance the healing response. This research sought to develop a non-destructive reticulation process for this SMP foam to disrupt the membranes between pore cells. Non-destructive mechanical reticulation was achieved using a gravity-driven floating nitinol pin array coupled with vibratory agitation of the foam and supplemental chemical etching. Lastly, reticulation resulted in a reduced elastic modulus and increased permeability, but did not impede the shape memory behavior. Reticulated foams were capable of achieving rapid vascular occlusion in an in vivo porcine model.

  15. Low-density, high-strength intermetallic matrix composites by XD (trademark) synthesis

    NASA Technical Reports Server (NTRS)

    Kumar, K. S.; Dipietro, M. S.; Brown, S. A.; Whittenberger, J. D.

    1991-01-01

    A feasibility study was conducted to evaluate the potential of particulate composites based on low-density, L1(sub 2) trialuminide matrices for high-temperature applications. The compounds evaluated included Al22Fe3Ti8 (as a multiphase matrix), Al67Ti25Cr8, and Al66Ti25Mn9. The reinforcement consisted of TiB2 particulates. The TiB2 composites were processed by ingot and powder metallurgy techniques. Microstructural characterization and mechanical testing were performed in the hot-pressed and hot-isostatic-pressed condition. The casting were sectioned and isothermally forged into pancakes. All the materials were tested in compression as a function of temperature, and at high temperatures as a function of strain rate. The test results are discussed.

  16. Evidence for liquid water during the high-density to low-density amorphous ice transition

    PubMed Central

    Kim, Chae Un; Barstow, Buz; Tate, Mark W.; Gruner, Sol M.

    2009-01-01

    Polymorphism of water has been extensively studied, but controversy still exists over the phase transition between high-density amorphous (HDA) and low-density amorphous (LDA) ice. We report the phase behavior of HDA ice inside high-pressure cryocooled protein crystals. Using X-ray diffraction, we demonstrate that the intermediate states in the temperature range from 80 to 170 K can be reconstructed as a linear combination of HDA and LDA ice, suggesting a first-order transition. We found evidence for a liquid state of water during the ice transition based on the protein crystallographic data. These observations open the possibility that the HDA ice induced by high-pressure cryocooling is a genuine glassy form of high-density liquid. PMID:19258453

  17. Buoyancy Effects on Flow Structure and Instability of Low-Density Gas Jets

    NASA Technical Reports Server (NTRS)

    Pasumarthi, Kasyap Sriramachandra

    2004-01-01

    A low-density gas jet injected into a high-density ambient gas is known to exhibit self-excited global oscillations accompanied by large vortical structures interacting with the flow field. The primary objective of the proposed research is to study buoyancy effects on the origin and nature of the flow instability and structure in the near-field of low-density gas jets. Quantitative rainbow schlieren deflectometry, Computational fluid dynamics (CFD) and Linear stability analysis were the techniques employed to scale the buoyancy effects. The formation and evolution of vortices and scalar structure of the flow field are investigated in buoyant helium jets discharged from a vertical tube into quiescent air. Oscillations at identical frequency were observed throughout the flow field. The evolving flow structure is described by helium mole percentage contours during an oscillation cycle. Instantaneous, mean, and RMS concentration profiles are presented to describe interactions of the vortex with the jet flow. Oscillations in a narrow wake region near the jet exit are shown to spread through the jet core near the downstream location of the vortex formation. The effects of jet Richardson number on characteristics of vortex and flow field are investigated and discussed. The laminar, axisymmetric, unsteady jet flow of helium injected into air was simulated using CFD. Global oscillations were observed in the flow field. The computed oscillation frequency agreed qualitatively with the experimentally measured frequency. Contours of helium concentration, vorticity and velocity provided information about the evolution and propagation of vortices in the oscillating flow field. Buoyancy effects on the instability mode were evaluated by rainbow schlieren flow visualization and concentration measurements in the near-field of self-excited helium jets undergoing gravitational change in the microgravity environment of 2.2s drop tower at NASA John H. Glenn Research Center. The jet

  18. Thermal inertia and radar reflectivity of the Martian north polar ERG: Low-density aggregates

    NASA Technical Reports Server (NTRS)

    Herkenhoff, K. E.

    1993-01-01

    The north pol