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Sample records for irbesartan suppressing atherosclerosis

  1. Irbesartan

    MedlinePLUS

    ... or in combination with other medications to treat high blood pressure. It is also used to treat kidney disease ... the amount of sugar in the blood) and high blood pressure. Irbesartan is in a class of medications called ...

  2. Irbesartan and Hydrochlorothiazide

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    Avalide® (as a combination product containing Irbesartan, Hydrochlorothiazide) ... Combination productThis product contains two medications, irbesartan and hydrochlorothiazide. Please see the individual monographs for information about ...

  3. Interleukin-10 overexpression in macrophages suppresses atherosclerosis in hyperlipidemic mice

    PubMed Central

    Han, Xinbing; Kitamoto, Shiro; Wang, Hongwei; Boisvert, William A.

    2010-01-01

    In atherogenesis, macrophage foam cell formation is modulated by pathways involving both the uptake and efflux of cholesterol. We recently showed that interleukin-10 (IL-10) modulates lipid metabolism by enhancing both uptake and efflux of cholesterol in macrophages. However, the mechanistic details of these properties in vivo have been unclear. Thus, the purpose of this study was to determine whether expression of IL-10 in macrophages would alter susceptibility to atherosclerosis and whether IL-10 exerts its antiatherosclerotic properties by modulating lipid metabolism in macrophages. We utilized a macrophage-specific retroviral vector that allows long-term in vivo expression of IL-10 in macrophages through transplantation of retrovirally transduced bone marrow cells (BMCs). IL-10 expressed by macrophages derived from transduced BMCs inhibited atherosclerosis in LDLR?/? mice by reducing cholesteryl ester accumulation in atherosclerotic sites. Experiments with primary macrophages indicated that macrophage source of IL-10 stimulated both the uptake (by up-regulating scavenger receptors) and efflux of cholesterol (by activating the PPAR?-LXR-ABCA1/ABCG1 pathway), thereby reducing inflammation and apoptosis in atherosclerosis. These findings indicate that BMC-transduced macrophage IL-10 production can act as a strong antiatherogenic agent, and they highlight a novel antiatherosclerotic therapy using a simple, yet effective, stem cell transduction system that facilitates long-term expression of IL-10 in macrophages.—Han, X., Kitamoto, S., Wang, H., Boisvert, W. A. Interleukin-10 overexpression in macrophages suppresses atherosclerosis in hyperlipidemic mice. PMID:20354139

  4. Atherosclerosis

    MedlinePLUS

    ... Pressure High Blood Pressure Tools & Resources Stroke More Atherosclerosis Updated:Jul 6,2015 View an animation of ... the arteries as you get older. How does atherosclerosis start and progress? It's a complex process. Exactly ...

  5. Atherosclerosis

    MedlinePLUS Videos and Cool Tools

    Normally, the walls of an artery are smooth, allowing blood to flow unimpeded. Atherosclerosis is when harmful material collects on the wall of an artery. This material includes fat, cholesterol, and ...

  6. Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages

    SciTech Connect

    Kinoshita, Hiroyuki; Matsumura, Takeshi; Ishii, Norio; Fukuda, Kazuki; Senokuchi, Takafumi; Motoshima, Hiroyuki; Kondo, Tatsuya; Taketa, Kayo; Kawasaki, Shuji; Hanatani, Satoko; Takeya, Motohiro; Nishikawa, Takeshi; Araki, Eiichi

    2013-02-08

    Highlights: ? We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ? Apocynin prevented atherosclerotic lesion formation. ? Apocynin suppressed ROS production in aorta and in macrophages. ? Apocynin suppressed cytokine expression and cell proliferation in macrophages. ? Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progression of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE{sup –/–}) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE{sup –/–} mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE{sup –/–} mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis.

  7. Flow-dependent expression of ectonucleotide tri(di)phosphohydrolase-1 and suppression of atherosclerosis

    PubMed Central

    Kanthi, Yogendra; Hyman, Matthew C.; Liao, Hui; Baek, Amy E.; Visovatti, Scott H.; Sutton, Nadia R.; Goonewardena, Sascha N.; Neral, Mithun K.; Jo, Hanjoong; Pinsky, David J.

    2015-01-01

    The ability of cells to detect and respond to nucleotide signals in the local microenvironment is essential for vascular homeostasis. The enzyme ectonucleotide tri(di)phosphohydrolase-1 (ENTPD1, also known as CD39) on the surface of leukocytes and endothelial cells metabolizes locally released, intravascular ATP and ADP, thereby eliminating these prothrombotic and proinflammatory stimuli. Here, we evaluated the contribution of CD39 to atherogenesis in the apolipoprotein E–deficient (ApoE-deficient) mouse model of atherosclerosis. Compared with control ApoE-deficient animals, plaque burden was markedly increased along with circulating markers of platelet activation in Cd39+/–Apoe–/– mice fed a high-fat diet. Plaque analysis revealed stark regionalization of endothelial CD39 expression and function in Apoe–/– mice, with CD39 prominently expressed in atheroprotective, stable flow regions and diminished in atheroprone areas subject to disturbed flow. In mice, disturbed flow as the result of partial carotid artery ligation rapidly suppressed endothelial CD39 expression. Moreover, unidirectional laminar shear stress induced atheroprotective CD39 expression in human endothelial cells. CD39 induction was dependent upon the vascular transcription factor Krüppel-like factor 2 (KLF2) binding near the transcriptional start site of CD39. Together, these data establish CD39 as a regionalized regulator of atherogenesis that is driven by shear stress. PMID:26121751

  8. Flow-dependent expression of ectonucleotide tri(di)phosphohydrolase-1 and suppression of atherosclerosis.

    PubMed

    Kanthi, Yogendra; Hyman, Matthew C; Liao, Hui; Baek, Amy E; Visovatti, Scott H; Sutton, Nadia R; Goonewardena, Sascha N; Neral, Mithun K; Jo, Hanjoong; Pinsky, David J

    2015-08-01

    The ability of cells to detect and respond to nucleotide signals in the local microenvironment is essential for vascular homeostasis. The enzyme ectonucleotide tri(di)phosphohydrolase-1 (ENTPD1, also known as CD39) on the surface of leukocytes and endothelial cells metabolizes locally released, intravascular ATP and ADP, thereby eliminating these prothrombotic and proinflammatory stimuli. Here, we evaluated the contribution of CD39 to atherogenesis in the apolipoprotein E-deficient (ApoE-deficient) mouse model of atherosclerosis. Compared with control ApoE-deficient animals, plaque burden was markedly increased along with circulating markers of platelet activation in Cd39+/-Apoe-/- mice fed a high-fat diet. Plaque analysis revealed stark regionalization of endothelial CD39 expression and function in Apoe-/- mice, with CD39 prominently expressed in atheroprotective, stable flow regions and diminished in atheroprone areas subject to disturbed flow. In mice, disturbed flow as the result of partial carotid artery ligation rapidly suppressed endothelial CD39 expression. Moreover, unidirectional laminar shear stress induced atheroprotective CD39 expression in human endothelial cells. CD39 induction was dependent upon the vascular transcription factor Krüppel-like factor 2 (KLF2) binding near the transcriptional start site of CD39. Together, these data establish CD39 as a regionalized regulator of atherogenesis that is driven by shear stress. PMID:26121751

  9. Ginkgo suppresses atherosclerosis through downregulating the expression of connexin 43 in rabbits

    PubMed Central

    Wang, Xin; Gong, Hui; Shi, Yi Jun; Zou, Yunzeng

    2013-01-01

    Introduction Ginkgo biloba extract (GBE) EGb761 is widely used for cardiovascular prevention. Here, we investigated the effects of GBE on atherosclerotic lesion development in rabbits with a high-fat diet. Material and methods Forty New Zealand white male rabbits were randomly divided into four groups. The first two were the normal diet group (C) and the high-fat group (HF). The remaining two groups were those who received a high cholesterol diet supplemented with either the standard drug (simvastatin 2 mg/kg/day) or GBE (3 mg/kg/day). At 12 weeks, histopathological and chemical analyses were performed. Results Plasma lipid measurement showed that GBE inhibited high-fat diet-induced increase of serum triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) by 59.1% (0.9 ±0.2 4 mmol/l vs. 2.2 ±0.4 mmol/l), 18.2% (31.1 ±1.4 mmol/l vs. 38.0 ±0.4 mmol/l) and 15% (28.9 ±1.3 mmol/l vs. 34.0±1.0 mmol/l), respectively, at 12 weeks (p < 0.01). The en face Sudan IV-positive lesion area of the aorta in the GBE group (51.7 ±3.1%) was significantly lower compared with that in the HF group (88.2 ±2.2%; p < 0.01). The mean atherosclerotic lesion area of the GBE group was reduced by 53.2% compared with the HF group (p < 0.01). Immunohistochemistry and western blot analysis showed that GBE markedly suppressed high-fat diet-induced upregulation of connexin 43 (Cx43) in rabbits (p < 0.01). Conclusions Thus, our study revealed that GBE prevented atherosclerosis progress through modulating plasma lipid, suppressing atherosclerotic lesion development, and attenuating the expression of Cx43 protein. PMID:23671447

  10. Endothelial NOTCH1 is suppressed by circulating lipids and antagonizes inflammation during atherosclerosis.

    PubMed

    Briot, Anaïs; Civelek, Mete; Seki, Atsuko; Hoi, Karen; Mack, Julia J; Lee, Stephen D; Kim, Jason; Hong, Cynthia; Yu, Jingjing; Fishbein, Gregory A; Vakili, Ladan; Fogelman, Alan M; Fishbein, Michael C; Lusis, Aldons J; Tontonoz, Peter; Navab, Mohamad; Berliner, Judith A; Iruela-Arispe, M Luisa

    2015-11-16

    Although much progress has been made in identifying the mechanisms that trigger endothelial activation and inflammatory cell recruitment during atherosclerosis, less is known about the intrinsic pathways that counteract these events. Here we identified NOTCH1 as an antagonist of endothelial cell (EC) activation. NOTCH1 was constitutively expressed by adult arterial endothelium, but levels were significantly reduced by high-fat diet. Furthermore, treatment of human aortic ECs (HAECs) with inflammatory lipids (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine [Ox-PAPC]) and proinflammatory cytokines (TNF and IL1?) decreased Notch1 expression and signaling in vitro through a mechanism that requires STAT3 activation. Reduction of NOTCH1 in HAECs by siRNA, in the absence of inflammatory lipids or cytokines, increased inflammatory molecules and binding of monocytes. Conversely, some of the effects mediated by Ox-PAPC were reversed by increased NOTCH1 signaling, suggesting a link between lipid-mediated inflammation and Notch1. Interestingly, reduction of NOTCH1 by Ox-PAPC in HAECs was associated with a genetic variant previously correlated to high-density lipoprotein in a human genome-wide association study. Finally, endothelial Notch1 heterozygous mice showed higher diet-induced atherosclerosis. Based on these findings, we propose that reduction of endothelial NOTCH1 is a predisposing factor in the onset of vascular inflammation and initiation of atherosclerosis. PMID:26552708

  11. Comprehensive overview: efficacy, tolerability, and cost-effectiveness of irbesartan

    PubMed Central

    Gialama, Fotini; Maniadakis, Nikos

    2013-01-01

    Background Hypertension represents a major health problem, affecting more than one billion adults worldwide. Irbesartan, an angiotensin II receptor blocker, is considered to be a highly effective treatment in the management of hypertension. The purpose of this review is to evaluate the efficacy, safety and tolerability profile , and cost-effectiveness of treatment with irbesartan in hypertension. Methods A review of the literature was conducted using the electronic PubMed and Cochrane Library databases and the Health Economic Evaluations Database of search terms relating to irbesartan efficacy, tolerability, and cost-effectiveness, and the results were utilized. Results Findings from the present analysis show that irbesartan either as monotherapy or in combination with other antihypertensive agents can achieve significant reductions in blood pressure, both systolic and diastolic, compared with alternative treatment options. Irbesartan was also found to have a renoprotective effect independent of its blood pressure-lowering in patients with type 2 diabetes and nephropathy. Furthermore, irbesartan demonstrated an excellent safety and tolerability profile , with either lower or equal adverse events compared with placebo and other alternative treatments. In terms of economic analyses, compared with other antihypertensive therapy alternatives, irbesartan was found to be a preferred option, that is less costly and more effective. Conclusion The evidence indicates that treating patients with hypertension alone or with type 2 diabetes and nephropathy using irbesartan can control hypertension, prolong life, and reduce costs in relation to existing alternatives. PMID:24124375

  12. Abscisic acid ameliorates atherosclerosis by suppressing macrophage and CD4+ T cell recruitment into the aortic wall

    PubMed Central

    Guri, Amir J.; Misyak, Sarah A.; Hontecillas, Raquel; Hasty, Alyssa; Liu, Dongmin; Si, Hongwei; Bassaganya-Riera, Josep

    2009-01-01

    Abscisic acid (ABA) is a natural phytohormone which improves insulin sensitivity and reduces adipose tissue inflammation when supplemented into diets of obese mice. The objective of this study was to investigate the mechanisms by which abscisic acid (ABA) prevents or ameliorates atherosclerosis. Apolipoprotein E-deficient (ApoE ?/?) mice were fed high-fat diets with or without ABA for 84 days. Systolic blood pressure was assessed on days 0, 28, 56, and 72. Gene expression, immune cell infiltration, and histological lesions were evaluated in the aortic root wall. Human aortic endothelial cells were used to examine the effect of ABA on 3’, 5’-cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) production in vitro. We report that ABA-treated mice had significantly improved systolic blood pressure and decreased accumulation of F4/80+CD11b+ macrophages and CD4+ T cells in aortic root walls. At the molecular level, ABA significantly enhanced aortic endothelial nitric oxide synthase (eNOS) and tended to suppress aortic vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression and plasma MCP-1 concentrations. ABA also caused a dose-dependent increase in intracellular concentrations of cAMP and NO and upregulated eNOS mRNA expression in human aortic endothelial cells. This is the first report showing that ABA prevents or ameliorates atherosclerosis-induced hypertension, immune cell recruitment into the aortic root wall, and upregulates aortic eNOS expression in ApoE?/? mice. PMID:20092994

  13. Novel angiotensin II AT(1) receptor antagonist irbesartan prevents thromboxane A(2)-induced vasoconstriction in canine coronary arteries and human platelet aggregation.

    PubMed

    Li, P; Fukuhara, M; Diz, D I; Ferrario, C M; Brosnihan, K B

    2000-01-01

    This study was conducted to investigate whether the novel orally active nonpeptide angiotensin II (Ang II) AT(1) receptor antagonist irbesartan interacts with the thromboxane A(2)/prostaglandin endoperoxide H(2) (TxA(2)/PGH(2)) receptor in canine coronary arteries and human platelets. Coronary artery rings were isolated from male dog hearts (n = 18) and isometric tension of vascular rings was measured continuously at optimal basal tension in organ chambers. Autoradiographic binding of [(3)H]SQ29,548, a TxA(2) receptor antagonist, in canine coronary sections was determined. Blood for platelet aggregation studies was collected by venous puncture from healthy human volunteers (n = 6) who were free of aspirin-like agents for at least 2 weeks. Vascular reactivity and platelet aggregation in response to the TxA(2) analogs U46619 and autoradioagraphic receptor binding to the TxA(2) receptor antagonist [(3)H]SQ29,548 were studied with and without irbesartan. The TxA(2) analog U46619 produced dose-dependent vasoconstriction in coronary rings (EC(50) = 11.6 +/- 1.5 nM). Pretreatment with irbesartan inhibited U46619-induced vasoconstriction, and the dose-response curve was shifted to the right in a dose-dependent manner. The EC(50) of U46619 was increased 6- and 35-fold in the presence of 1 and 10 microM of irbesartan without a change of maximal contraction. At 1 microM, irbesartan is 2-fold more potent than the AT(1) receptor antagonist losartan in the inhibition of U46619-induced vasoconstriction in canine coronary arteries. In contrast, neither AT(1) receptor antagonists (CV11974 and valsartan), the AT(2) receptor antagonist PD123319, nor the angiotensin converting enzyme inhibitor lisinopril had any effect on U46619-induced coronary vasoconstriction. Irbesartan did not change potassium chloride-induced vasoconstriction; however, irbesartan did inhibit the vasoconstriction mediated by another TxA(2)/PGH(2) receptor agonist prostaglandin F(2alpha) (PGF(2alpha)). Neither the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester nor the cyclooxygenase inhibitor indomethacin had any effect on irbesartan's attenuation of U46619-induced vasoconstriction. Irbesartan specifically reversed U46619-preconstricted coronary artery rings with and without endothelium in a dose-dependent manner. Irbesartan at high concentrations significantly competed for [(3)H]SQ29,548 binding in canine coronary sections. U46619 stimulated dose-dependent human platelet aggregation of platelet-rich plasma. Preincubation with irbesartan significantly inhibited platelet aggregation in a concentration-dependent manner. In conclusion, the dual antagonistic actions of irbesartan by acting at both the AT(1) and TxA(2) receptors in blood vessels and platelets may overall enhance its therapeutic profile in the treatment of hypertension, atherosclerosis, and arterial thrombosis. PMID:10604953

  14. Fibroblast Growth Factor 21 Prevents Atherosclerosis by Suppression of Hepatic Sterol Regulatory Element-Binding Protein-2 and Induction of Adiponectin in Mice

    PubMed Central

    Lin, Zhuofeng; Pan, Xuebo; Wu, Fan; Ye, Dewei; Zhang, Yi; Wang, Yu; Jin, Leigang; Lian, Qizhou; Huang, Yu; Ding, Hong; Triggle, Chris; Wang, Kai

    2015-01-01

    Background— Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity. It acts as a key downstream target of both peroxisome proliferator-activated receptor ? and ?, the agonists of which have been used for lipid lowering and insulin sensitization, respectively. However, the role of FGF21 in the cardiovascular system remains elusive. Methods and Results— The roles of FGF21 in atherosclerosis were investigated by evaluating the impact of FGF21 deficiency and replenishment with recombinant FGF21 in apolipoprotein E?/? mice. FGF21 deficiency causes a marked exacerbation of atherosclerotic plaque formation and premature death in apolipoprotein E?/? mice, which is accompanied by hypoadiponectinemia and severe hypercholesterolemia. Replenishment of FGF21 protects against atherosclerosis in apolipoprotein E?/?mice via 2 independent mechanisms, inducing the adipocyte production of adiponectin, which in turn acts on the blood vessels to inhibit neointima formation and macrophage inflammation, and suppressing the hepatic expression of the transcription factor sterol regulatory element-binding protein-2, thereby leading to reduced cholesterol synthesis and attenuation of hypercholesterolemia. Chronic treatment with adiponectin partially reverses atherosclerosis without obvious effects on hypercholesterolemia in FGF21-deficient apolipoprotein E?/? mice. By contrast, the cholesterol-lowering effects of FGF21 are abrogated by hepatic expression of sterol regulatory element-binding protein-2. Conclusions— FGF21 protects against atherosclerosis via fine tuning the multiorgan crosstalk among liver, adipose tissue, and blood vessels. PMID:25794851

  15. 77 FR 1695 - Determination That AVALIDE (Hydrochlorothiazide and Irbesartan), Oral Tablets, 25 Milligrams/300...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... SERVICES Food and Drug Administration Determination That AVALIDE (Hydrochlorothiazide and Irbesartan), Oral... Food and Drug Administration (FDA) has determined that AVALIDE (hydrochlorothiazide and irbesartan... (ANDAs) for hydrochlorothiazide and irbesartan, oral tablets, 25 mg/300 mg and 12.5 mg/75 mg, if...

  16. Atherosclerosis (image)

    MedlinePLUS

    Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, ... muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

  17. Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

    SciTech Connect

    Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo; Horiuchi, Masatsugu

    2011-03-04

    Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

  18. Imaging Atherosclerosis

    E-print Network

    Tarkin, Jason M.; Dweck, Marc R.; Evans, Nicholas R.; Takx, Richard A. P.; Brown, Adam J.; Tawakol, Ahmed; Fayad, Zahi A.; Rudd, James H. F.

    2015-01-01

    Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however these important vascular imaging methods additionally promise great scientific and translational...

  19. Amelioration of Hyperglycemia with a Sodium-Glucose Cotransporter 2 Inhibitor Prevents Macrophage-Driven Atherosclerosis through Macrophage Foam Cell Formation Suppression in Type 1 and Type 2 Diabetic Mice

    PubMed Central

    Terasaki, Michishige; Hiromura, Munenori; Mori, Yusaku; Kohashi, Kyoko; Nagashima, Masaharu; Kushima, Hideki; Watanabe, Takuya; Hirano, Tsutomu

    2015-01-01

    Direct associations between hyperglycemia and atherosclerosis remain unclear. We investigated the association between the amelioration of glycemia by sodium-glucose cotransporter 2 inhibitors (SGLT2is) and macrophage-driven atherosclerosis in diabetic mice. We administered dapagliflozin or ipragliflozin (1.0 mg/kg/day) for 4-weeks to apolipoprotein E-null (Apoe?/?) mice, streptozotocin-induced diabetic Apoe?/? mice, and diabetic db/db mice. We then determined aortic atherosclerosis, oxidized low-density lipoprotein (LDL)-induced foam cell formation, and related gene expression in exudate peritoneal macrophages. Dapagliflozin substantially decreased glycated hemoglobin (HbA1c) and glucose tolerance without affecting body weight, blood pressure, plasma insulin, and lipids in diabetic Apoe?/? mice. Aortic atherosclerotic lesions, atheromatous plaque size, and macrophage infiltration in the aortic root increased in diabetic Apoe?/? mice; dapagliflozin attenuated these changes by 33%, 27%, and 20%, respectively. Atherosclerotic lesions or foam cell formation highly correlated with HbA1c. Dapagliflozin did not affect atherosclerosis or plasma parameters in non-diabetic Apoe?/? mice. In db/db mice, foam cell formation increased by 4-fold compared with C57/BL6 mice, whereas ipragliflozin decreased it by 31%. Foam cell formation exhibited a strong correlation with HbA1c. Gene expression of lectin-like ox-LDL receptor-1 and acyl-coenzyme A:cholesterol acyltransferase 1 was upregulated, whereas that of ATP-binding cassette transporter A1 was downregulated in the peritoneal macrophages of both types of diabetic mice. SGLT2i normalized these gene expressions. Our study is the first to demonstrate that SGLT2i exerts anti-atherogenic effects by pure glucose lowering independent of insulin action in diabetic mice through suppressing macrophage foam cell formation, suggesting that foam cell formation is highly sensitive to glycemia ex vivo. PMID:26606676

  20. What Causes Atherosclerosis?

    MedlinePLUS

    ... page from the NHLBI on Twitter. What Causes Atherosclerosis? The exact cause of atherosclerosis isn't known. ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  1. How Is Atherosclerosis Diagnosed?

    MedlinePLUS

    ... page from the NHLBI on Twitter. How Is Atherosclerosis Diagnosed? Your doctor will diagnose atherosclerosis based on ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  2. Mesenteric artery remodeling and effects of imidapril and irbesartan on it in spontaneously hypertensive rats

    PubMed Central

    Zhu, Zhong-Sheng; Wang, Jin-Ming; Chen, Shao-Liang

    2004-01-01

    AIM: To investigate the remodeling of mesenteric artery and the expression of TGF-?1, c-Jun in mesenteric artery and effects of imidapril and irbesartan on the remodeling in spontaneously hypertensive rats (SHR). METHODS: Thirty SHR (male/female, 21/9), aged 13 wk, were randomly divided into 3 groups (7 male rats and 3 female rats each group): SHR group, imidapril group (imidapril 3 mg/kg·d was given in drinking water for 14 wk), and irbesartan group (irbesartan 50 mg/kg·d was given in drinking water foe 14 wk). Ten homogenous Wistar Kyoto rats, 5 males and 5 females, weighing 206 ± 49 g, were selected as normal control group (WKY group). Systolic pressure was measured on day 1, 2, 4, 6, 8, 10, 12 and 14 during the experiment and the rats were killed at the end of the experiment. Angiotensin II (Ang II) level in plasma and mesenteric arteries was measured by radioimmunoassay. The morphology of the secondary branches of mesenteric artery were examined by light microscopy and electron microscopy. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of transforming growth factor TGF-?1 and c-Jun mRNA. RESULTS: Compared with imidapril group and irbesartan group, the blood pressure was remarkably increased in SHR group. Ang II level in plasma and mesenteric arteries in SHR group was the same or lower than that in WKY group, and was higher in irbesartan group and lower in imidapril group. The remodeling of mesenteric arteries in SHR group was mostly obvious among the 4 groups. The ratio of TGF-?1 absorbed light value to GAPDH absorbed light value in the SHR group was 0.887 ± 0.019, which was significantly higher than that in WKY group, imidapril group, and irbesartan group with the ratios of 0.780 ± 0.018, 0.803 ± 0.005, and 0.847 ± 0.017, respectively (P < 0.01). Ang II level in plasma and mesenteric arteries in imidapril group was significantly lower than that in irbesartan group (P < 0.05). The c-Jun absorbed light value/GAPDH absorbed light value of mesenteric arteries in the SHR group was 0.850 ± 0.015, which was significantly higher than that in the WKY, imidapril, and irbesartan groups (0.582 ± 0.013, 0.743 ± 0.012, and 0.789 ± 0.013, respectively, P < 0.01), and was significantly lower in imidapril group than in irbesartan group (P < 0.05). CONCLUSION: Imidapril and irbesartan can not only control blood pressure but also inhibit mesenteric arteries remodeling and mRNA expression of TGF-?1, c-Jun in SHR. Imidapril is more effective than irbesartan. PMID:15133856

  3. Effects of low-dose spironolactone combined with irbesartan on cardiac hypertrophy induced by pressure overload in rats

    PubMed Central

    Ma, Jingtao; Zhang, Hongxue; Guo, Huicai; Xu, Yanfang

    2014-01-01

    Background: The mineralocorticoid receptor (MR) blockade in the heart is an attractive therapeutic option for the treatment of heart failure. However, the use of MR antagonist is limited by an increased incidence of hyperkalemia owing to MR blockade in the kidney. This study was designed to evaluate and compare the effectiveness of a low, non-pressure-lowering dose of spironolactone (Sp) with that of a conventional blood pressure-lowering dose combined with irbesartan on pathological cardiac remodeling as well as serum potassium level in pressure-overload rats. Methods: The pressure-overloaded myocardial remodelling was produced by partial abdominal aortic constriction (PAAC) in rats. Four weeks after PAAC, animals were respectively treated with vehicle, irbesartan (15 mg/kg) alone, low-dose Sp (1 mg/kg) or conventional-dose of Sp (20 mg/kg) in combination with irbesartan for consecutive four weeks. Results: The result demonstrated that compared to irbesartan monotherapy, the combination of irbesartan and spironolactone both in low- and conventional-dose exhibited additional cardioprotection against PAAC-induced cardiac remodelling. Low-dose spironolactone was as effective in inhibiting cardiac hypertrophy, fibrosis and in improving diastolic function as high dose. Low-dose spironolactone did not lead to a rise in potassium serum levels, but high dose did. Conclusions: This study suggests that combined low dose of spironolactone and irbesartan may be an effective and safety therapeutic strategy for cardiac hypertrophy and heart failure. PMID:25628791

  4. Living with Atherosclerosis

    MedlinePLUS

    ... page from the NHLBI on Twitter. Living With Atherosclerosis Improved treatments have reduced the number of deaths ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  5. Hepatic Overexpression of Soluble Urokinase Receptor (uPAR) Suppresses Diet-Induced Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient (LDLR-/-) Mice

    PubMed Central

    Janssen, Henrike; Müller, Martin; Herzog, Christine; Lorenz, Anika; Schmitz, Martina; Nofer, Jerzy-Roch; Theilmeier, Gregor

    2015-01-01

    Objective Atherosclerosis, a chronic inflammatory disease, arises from metabolic disorders and is driven by inappropriate recruitment and proliferation of monocytes / macrophages and vascular smooth-muscle-cells. The receptor for the urokinase-type plasminogen activator (uPAR, Plaur) regulates the proteolytic activation of plasminogen. It is also a coactivator of integrins and facilitates leukocyte-endothelial interactions and vascular smooth-muscle-cell migration. The role of uPAR in atherogenesis remains elusive. Methods and Results We generated C57Bl6/J low-density lipoprotein receptor (LDL) and uPAR double knockout (uPAR-/-/LDLR-/-) mice to test the role of uPAR in two distinct atherosclerosis models. In LDLR-/- mice, hepatic overexpression following hydrodynamic transfection of soluble uPAR that competes with endogenous membrane-bound uPAR was performed as an interventional strategy. Aortic root atherosclerotic lesions induced by feeding a high-fat diet were smaller and comprised less macrophages and vascular smooth-muscle-cells in double knockout mice and animals overexpressing soluble uPAR when compared to controls. In contrast, lesion size, lipid-, macrophage-, and vascular smooth muscle cell content of guide-wire-induced intima lesions in the carotid artery were not affected by uPAR deficiency. Adhesion of uPAR-/--macrophages to TNF?-stimulated endothelial cells was decreased in vitro accompanied by reduced VCAM-1 expression on primary endothelial cells. Hepatic overexpression of soluble full-length murine uPAR in LDLR-/- mice led to a reduction of diet-induced atherosclerotic lesion formation and monocyte recruitment into plaques. Ex vivo incubation with soluble uPAR protein also inhibited adhesion of macrophages to TNF?-stimulated endothelial cells in vitro. Conclusion uPAR-deficiency as well as competitive soluble uPAR reduced diet-promoted but not guide-wire induced atherosclerotic lesions in mice by preventing monocyte recruitment and vascular smooth-muscle-cell infiltration. Soluble uPAR may represent a therapeutic tool for the modulation of hyperlipidemia-associated atherosclerotic lesion formation. PMID:26313756

  6. Impact of irbesartan, an angiotensin receptor blocker, on uric acid level and oxidative stress in high-risk hypertension patients.

    PubMed

    Chida, Ryuji; Hisauchi, Itaru; Toyoda, Shigeru; Kikuchi, Migaku; Komatsu, Takaaki; Hori, Yuichi; Nakahara, Shiro; Sakai, Yoshihiko; Inoue, Teruo; Taguchi, Isao

    2015-11-01

    Hyperuricemia is a known cardiovascular risk factor. The angiotensin II receptor blocker (ARB) losartan is known to decrease serum uric acid (UA) level. A recent in vitro study demonstrated a strong interaction between irbesartan and UA transporters that exceeded that of losartan. The purpose of the present study was to evaluate the hypouricemic effect of irbesartan in a clinical setting. A total of 40 high-risk hypertensive outpatients with coronary artery disease, cerebrovascular disease and/or diabetes complications who were taking ARBs other than irbesartan and losartan were enrolled in this study. After a 4-week control period, the patients' prescribed ARBs were exchanged for an equivalent dose of irbesartan. We assessed blood pressure, heart rate, serum UA level, parameters of lipid and glucose metabolism, cardiac and renal function and inflammatory and oxidative stress markers in blood samples taken immediately before the initiation of irbesartan treatment and again after 12 weeks of treatment. All 40 recruited patients were followed (31 men and 9 women, mean age: 68 years) without any dropouts. During the 12 weeks of irbesartan treatment, no significant changes in blood pressure, heart rate, parameters of lipid or glucose metabolism or other biomarkers of cardiac function, renal function, or inflammation were observed. However, UA level (5.9±1.6 to 5.5±1.6?mg?ml(-1), P=0.028) and the oxidative stress marker derivative reactive oxygen metabolites (dROMs) (354±83 to 310±65?U.CARR, P<0.001) were significantly lower at 12 weeks of treatment compared with before treatment. These results suggest that irbesartan has beneficial effects on hyperuricemia and oxidative stress. PMID:26178150

  7. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    SciTech Connect

    Cai, Yujun; Li, Jian-Dong; Yan, Chen

    2013-05-10

    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

  8. Intracranial atherosclerosis following radiotherapy

    SciTech Connect

    Werner, M.H.; Burger, P.C.; Heinz, E.R.; Friedman, A.H.; Halperin, E.C.; Schold, S.C. Jr.

    1988-07-01

    We describe a case of severe intracranial atherosclerosis in a young man who had received therapeutic radiation for a presumed brain neoplasm. Since there was no evidence of vascular disease outside the radiation ports, we speculate that accelerated atherosclerosis was induced by radiation and that hyperlipidemia may have predisposed him to this effect.

  9. Angiotensin II and atherosclerosis.

    PubMed

    Weiss, D; Sorescu, D; Taylor, W R

    2001-04-19

    Numerous clinical and laboratory data are now available supporting the hypothesis that the renin-angiotensin system is mechanistically relevant in the pathogenesis of atherosclerosis. The traditional role of the renin-angiotensin system in the context of blood pressure regulation has been modified to incorporate the concept that angiotensin II (Ang II) is a potent proinflammatory agent. In vascular cells, Ang II is a potent stimulus for the generation of reactive oxygen species. As a result, Ang II upregulates the expression of many redox-sensitive cytokines, chemokines, and growth factors that have been implicated in the pathogenesis of atherosclerosis. Extensive data now confirm that inhibition of the renin-angiotensin system inhibits atherosclerosis in animal models as well as in humans. These studies provide mechanistic insights into the precise role of Ang II in atherosclerosis and suggest that pharmacologic interventions involving the renin-angiotensin system may be of fundamental importance in the treatment and prevention of atherosclerosis. PMID:11334765

  10. Animal models of atherosclerosis.

    PubMed

    Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Chen, Li; Uitz, Elisabeth; Bahadori, Babak; Moghadasian, Mohammed H

    2014-05-16

    In this mini-review several commonly used animal models of atherosclerosis have been discussed. Among them, emphasis has been made on mice, rabbits, pigs and non-human primates. Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions, we still lack a reliable animal model for regression of the disease. Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis, however each of current animal models have some limitations. Among these animal models, the apolipoprotein (apo) E-knockout (KO) mice have been used extensively because they develop spontaneous atherosclerosis. Furthermore, atherosclerotic lesions developed in this model depending on experimental design may resemble humans' stable and unstable atherosclerotic lesions. This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis. Low density lipoprotein (LDL)-r-KO mice are a model of human familial hypercholesterolemia. However, unlike apo E-KO mice, the LDL-r-KO mice do not develop spontaneous atherosclerosis. Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies. In addition to mice, rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis. The present review paper details the characteristics of animal models that are used in atherosclerosis research. PMID:24868511

  11. Animal models of atherosclerosis

    PubMed Central

    Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Chen, Li; Uitz, Elisabeth; Bahadori, Babak; Moghadasian, Mohammed H

    2014-01-01

    In this mini-review several commonly used animal models of atherosclerosis have been discussed. Among them, emphasis has been made on mice, rabbits, pigs and non-human primates. Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions, we still lack a reliable animal model for regression of the disease. Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis, however each of current animal models have some limitations. Among these animal models, the apolipoprotein (apo) E-knockout (KO) mice have been used extensively because they develop spontaneous atherosclerosis. Furthermore, atherosclerotic lesions developed in this model depending on experimental design may resemble humans’ stable and unstable atherosclerotic lesions. This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis. Low density lipoprotein (LDL)-r-KO mice are a model of human familial hypercholesterolemia. However, unlike apo E-KO mice, the LDL-r-KO mice do not develop spontaneous atherosclerosis. Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies. In addition to mice, rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis. The present review paper details the characteristics of animal models that are used in atherosclerosis research. PMID:24868511

  12. HIV and Atherosclerosis

    MedlinePLUS

    ... Pressure High Blood Pressure Tools & Resources Stroke More HIV and Atherosclerosis Updated:Jan 22,2014 Featured Video ... improve your cholesterol ratios, with or without HIV. HIV and Your Heart • Home • About HIV • HIV and ...

  13. Nutrition and Atherosclerosis.

    PubMed

    Torres, Nimbe; Guevara-Cruz, Martha; Velázquez-Villegas, Laura A; Tovar, Armando R

    2015-07-01

    Cardiovascular disease (CVD) is a universal problem in modern society. Atherosclerosis is the leading cause of CVD resulting in high rate of mortality in the population. Nutrition science has focused on the role of essential nutrients in preventing deficiencies, at the present time, the nutritional strategies are crucial to promote health and intervene with these global noncommunicable diseases. In many cases, diet is a major driving force, which is much easier to change and follow than other factors. It is important to establish that the first strategy to treat atherosclerosis is to modify lifestyle habits, focusing on the beneficial properties of specific nutrients. In the last decades, epidemiological, clinical and experimental studies have demonstrated that diet plays a central role in the prevention of atherosclerosis. In this review we will focus on the effect of specific foods, nutrients and bioactive compounds, including epidemiological facts, potential mechanisms of action and dietary recommendations to reduce the risk of atherosclerosis. In particular, we include information about fiber, plant sterols and stanols, niacin, taurine, olive oil, omega 3 fatty acids, antioxidants, minerals, methyl nutrients and soy. In addition, we also show that dysbiosis of the intestinal microbiota associated with a consumption of certain animal food sources can generate some metabolites that are involved in the development of atherosclerosis and its consequences on CVD. According to the epidemiological, clinical and experimental studies we suggest a recommendation for some dietary foods, nutrients and bioactive compounds to support the complementary clinical management of patients with atherosclerosis. PMID:26031780

  14. Molecular imaging in atherosclerosis

    PubMed Central

    Glaudemans, Andor W. J. M.; Slart, Riemer H. J. A.; Bozzao, Alessandro; Bonanno, Elena; Arca, Marcello; Dierckx, Rudi A. J. O.

    2010-01-01

    Atherosclerosis is the major cause of cardiovascular disease, which still has the leading position in morbidity and mortality in the Western world. Many risk factors and pathobiological processes are acting together in the development of atherosclerosis. This leads to different remodelling stages (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat cardiovascular disease. PMID:20306036

  15. Irbesartan/HCTZ fixed combinations in patients of different racial/ethnic groups with uncontrolled systolic blood pressure on monotherapy.

    PubMed Central

    Ofili, Elizabeth O.; Ferdinand, Keith C.; Saunders, Elijah; Neutel, Joel M.; Bakris, George L.; Cushman, William C.; Sowers, James R.; Weber, Michael A.

    2006-01-01

    The IrbesartaN/hydroChlorothiazide (HCTZ) bLood pressUre reductionS In diVErse patient populations (INCLUSIVE) trial was a multicenter, prospective, open-label, single-arm study evaluating the efficacy and safety of irbesartan/HCTZ fixed combinations in patients > or = 18 years old with uncontrolled systolic blood pressure (SBP, 140-159 mmHg; 130-159 mmHg for type-2 diabetes mellitus patients) after > or = 4 weeks of antihypertensive monotherapy. This analysis focused on different racial/ethnic subgroups. Treatment was sequential: placebo (4-5 weeks), HCTZ 12.5 mg (two weeks), irbesartan/HCTZ 150/12.5 mg (eight weeks) and irbesartan/HCTZ 300/25 mg (eight weeks). Overall, 515 Caucasians, 191 African Americans and 119 Hispanics/Latinos completing placebo treatment were enrolled. Mean SBP changes from baseline (placebo treatment end) to week 18 were -21.5 +/- 13.8 mmHg for Caucasians, -20.7 +/- 16.5 mmHg for African Americans and -22.9 +/- 13.2 mmHg for Hispanics/Latinos, respectively (p<0.001 for each). Mean diastolic BP (DBP) changes were statistically significant (p<0.001) and similar among racial/ethnic subgroups. By week 18, 70% (95% CI, 66%, 74%) of Caucasian, 66% (95% CI, 59%, 74%) of African-American and 65% (95% CI, 57%, 74%) of Hispanic/Latino patients achieved dual SBP/DBP goal. Treatments appeared to be well tolerated. In conclusion, irbesartan/HCTZ treatment provided SBP/DBP goal attainment in approximately two-thirds of Caucasian, African-American and Hispanic/Latino patients with SBP uncontrolled on antihypertensive monotherapy. PMID:16623075

  16. Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism

    SciTech Connect

    Cheng, Tain-Junn; Chuu, Jiunn-Jye; Chang, Chia-Yu; Tsai, Wan-Chen; Chen, Kuan-Jung; Guo, How-Ran

    2011-10-15

    Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor {beta} (LXR{beta}) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXR{beta} activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXR{beta} and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element. - Highlights: > Arsenic causes cardiovascular and cerebrovascular diseases through atherosclerosis. > Arsenic may promote atherosclerosis with transient increase in HSP 70 and hs-CRP. > Arsenic exposure and high cholesterol diet early in life suppress CEPT-1 and LXR? > Arsenic may induce atherosclerosis by modifying reverse cholesterol transport. > Prevent arsenic exposure in early life is important to decreasing atherosclerosis.

  17. Myocardial infarction accelerates atherosclerosis

    PubMed Central

    Dutta, Partha; Courties, Gabriel; Wei, Ying; Leuschner, Florian; Gorbatov, Rostic; Robbins, Clinton; Iwamoto, Yoshiko; Thompson, Brian; Carlson, Alicia L.; Heidt, Timo; Majmudar, Maulik D.; Lasitschka, Felix; Etzrodt, Martin; Waterman, Peter; Waring, Michael T.; Chicoine, Adam T.; van der Laan, Anja M.; Niessen, Hans W.M.; Piek, Jan J.; Rubin, Barry B.; Butany, Jagdish; Stone, James; Katus, Hugo A.; Murphy, Sabina A.; Morrow, David A.; Sabatine, Marc S.; Vinegoni, Claudio; Moskowitz, Michael A.; Pittet, Mikael J.; Libby, Peter; Lin, Charles P.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias

    2012-01-01

    SUMMARY During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaque in the arterial wall and cause its rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, apoE?/? mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. When seeking the source of surplus monocytes in plaque, we found that myocardial infarction liberated hematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signaling. The progenitors then seeded the spleen yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression. PMID:22763456

  18. Myocardial infarction accelerates atherosclerosis.

    PubMed

    Dutta, Partha; Courties, Gabriel; Wei, Ying; Leuschner, Florian; Gorbatov, Rostic; Robbins, Clinton S; Iwamoto, Yoshiko; Thompson, Brian; Carlson, Alicia L; Heidt, Timo; Majmudar, Maulik D; Lasitschka, Felix; Etzrodt, Martin; Waterman, Peter; Waring, Michael T; Chicoine, Adam T; van der Laan, Anja M; Niessen, Hans W M; Piek, Jan J; Rubin, Barry B; Butany, Jagdish; Stone, James R; Katus, Hugo A; Murphy, Sabina A; Morrow, David A; Sabatine, Marc S; Vinegoni, Claudio; Moskowitz, Michael A; Pittet, Mikael J; Libby, Peter; Lin, Charles P; Swirski, Filip K; Weissleder, Ralph; Nahrendorf, Matthias

    2012-07-19

    During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression. PMID:22763456

  19. [Oxidative stress and atherosclerosis].

    PubMed

    Stark, Júlia

    2015-07-12

    Atherosclerosis is a leading cause of death in developed countries. Genetic susceptibility and environmental factors play a role in the pathogenesis. Most of these factors lead to endothelial dysfunction and other pro-atherogenic processes by causing oxidative stress. Atherosclerosis typically develops at the curved and branched regions of the arterial tree, where the laminar blood flow is disturbed. This leads to increased permeability of the endothelium to low density lipoprotein molecules, which accumulate in the intima and are oxidised by vascular cells. Oxidised low density lipoprotein takes part in many phases of atherogenesis: stimulates the binding of monocytes to the endothelium, foam cell formation, the development of plaques, plaque destabilization and thrombotic complications. Since oxidative stress plays an important role in atherogenesis, it has been suggested that antioxidant molecules might have anti-atherogenic function. Many clinical investigations have shown that antioxidants such as N-acetylcystein, vitamin E and C, folic acid, and estrogens can prevent atherosclerosis, however, randomized studies failed to confirm this effect. PMID:26149503

  20. Systematic Approach for Trace Level Quantification of 2-N-butyl-4-spirocyclopentane-2-imidazole-5-one Genotoxic Impurity in Irbesartan Using LC-MS/MS

    PubMed Central

    Reddy, A. Vijaya Bhaskar; Venugopal, N.; Madhavi, G.; Madhavi, V.; Reddy, K. Gangadhara

    2013-01-01

    2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one has been highlighted as a potential genotoxic impurity in irbesartan. A sensitive LC-MS/MS method was developed and validated for the determination of 2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one in irbesartan. Good separation between 2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one and irbesartan was achieved with Symmetry C18 (100×4.6 mm, 3.5 ?m) column using 65:35 v/v mixture of 0.1% formic acid and acetonitrile as mobile phase with a flow rate of 0.7 ml/min. The proposed method was specific, linear, accurate, and precise. The calibration curve shows good linearity over the concentration range of 0.1-2.0 ?g/ml, which matches the range of limit of quantitation-20×limit of quantitation of estimated permitted level (1.0 ?g/ml) of 2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one. The method was validated as per International Conference on Harmonization guidelines and was able to quantitate 2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one impurity at 1.0 ?g/ml with respect to 2 mg/ml of irbesartan. 2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one was not present in the three studied pure and formulation batches of irbesartan and the developed method was a good quality control tool for quantitation of 2-N-butyl-4-spirocyclopentane-2-imidazole-5-one at very low levels in irbesartan. PMID:24403649

  1. Modeling Lesion Growth in Atherosclerosis Kyle Thicke

    E-print Network

    Rowell, Eric C.

    Modeling Lesion Growth in Atherosclerosis Kyle Thicke July 19, 2013 #12;Definitions Atherosclerosis cells (foam cells) in the artery wall Atherogensis The start of atherosclerosis A lesion starts growing

  2. B Cell Subsets in Atherosclerosis

    PubMed Central

    Perry, Heather M.; Bender, Timothy P.; McNamara, Coleen A.

    2012-01-01

    Atherosclerosis, the underlying cause of heart attacks and strokes, is a chronic inflammatory disease of the artery wall. Immune cells, including lymphocytes modulate atherosclerotic lesion development through interconnected mechanisms. Elegant studies over the past decades have begun to unravel a role for B cells in atherosclerosis. Recent findings provide evidence that B cell effects on atherosclerosis may be subset-dependent. B-1a B cells have been reported to protect from atherosclerosis by secretion of natural IgM antibodies. Conventional B-2 B cells can promote atherosclerosis through less clearly defined mechanism that may involve CD4 T cells. Yet, there may be other populations of B cells within these subsets with different phenotypes altering their impact on atherosclerosis. Additionally, the role of B cell subsets in atherosclerosis may depend on their environmental niche and/or the stage of atherogenesis. This review will highlight key findings in the evolving field of B cells and atherosclerosis and touch on the potential and importance of translating these findings to human disease. PMID:23248624

  3. Neutrophil's weapons in atherosclerosis.

    PubMed

    Chistiakov, Dimitry A; Bobryshev, Yuri V; Orekhov, Alexander N

    2015-12-01

    Neutrophils are important components of immunity associated with inflammatory responses against a broad spectrum of pathogens. These cells could be rapidly activated by proinflammatory stimuli and migrate to the inflamed and infected sites where they release a variety of cytotoxic molecules with antimicrobial activity. Neutrophil antibacterial factors include extracellular proteases, redox enzymes, antimicrobial peptides, and small bioactive molecules. In resting neutrophils, these factors are stored in granules and released upon activation during degranulation. These factors could be also secreted in a neutrophil-derived microparticle-dependent fashion. Neutrophils exhibit a unique property to produce neutrophil extracellular traps (NETs) composed of decondensed chromatin and granular proteins to catch and kill bacteria. Neutrophil-released factors are efficient in inactivation and elimination of pathogens through oxidation-dependent or independent damage of bacterial cells, inactivation and neutralization of virulence factors and other mechanisms. However, in chronic atherosclerosis-associated inflammation, protective function of neutrophils could be impaired and misdirected against own cells. This could lead to deleterious effects and progressive vascular injury. In atherogenesis, a pathogenic role of neutrophils could be especially seen in early stages associated with endothelial dysfunction and induction of vascular inflammation and in late atherosclerosis associated with plaque rupture and atherothrombosis. Assuming a prominent impact of neutrophils in cardiovascular pathology, developing therapeutic strategies targeting neutrophil-specific antigens could have a promising clinical potential. PMID:26551083

  4. Telomeres and atherosclerosis.

    PubMed

    Khan, S; Chuturgoon, A A; Naidoo, D P

    2012-11-01

    In humans and other multicellular organisms that have an extended lifespan, the leading causes of death are atherosclerotic cardiovascular disease and cancer. Experimental and clinical evidence indicates that these age-related disorders are linked through dysregulation of telomere homeostasis. Telomeres are DNA protein structures located at the terminal end of chromosomes and shorten with each cycle of cell replication, thereby reflecting the biological age of an organism. Critically shortened telomeres provoke cellular senescence and apoptosis, impairing the function and viability of a cell. The endothelial cells within atherosclerotic plaques have been shown to display features of cellular senescence. Studies have consistently demonstrated an association between shortened telomere length and coronary artery disease (CAD). Several of the CAD risk factors and particularly type 2 diabetes are linked to telomere shortening and cellular senescence. Our interest in telomere biology was prompted by the high incidence of premature CAD and diabetes in a subset of our population, and the hypothesis that these conditions are premature-ageing syndromes. The assessment of telomere length may serve as a better predictor of cardiovascular risk and mortality than currently available risk markers, and anti-senescence therapy targeting the telomere complex is emerging as a new strategy in the treatment of atherosclerosis. We review the evidence linking telomere biology to atherosclerosis and discuss methods to preserve telomere length. PMID:23192261

  5. Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice.

    PubMed

    Hirase, Tetsuaki; Hara, Hiromitsu; Miyazaki, Yoshiyuki; Ide, Noriko; Nishimoto-Hazuku, Ai; Fujimoto, Hirokazu; Saris, Christiaan J M; Yoshida, Hiroki; Node, Koichi

    2013-08-01

    Chronic inflammation in arterial wall that is driven by immune cells and cytokines plays pivotal roles in the development of atherosclerosis. Interleukin 27 (IL-27) is a member of the IL-12 family of cytokines that consists of IL-27p28 and Epstein-Barr virus induced gene 3 (EBI3) and has anti-inflammatory properties that regulate T cell polarization and cytokine production. IL-27-deficient (Ldlr-/-Ebi3-/-) and IL-27 receptor-deficient (Ldlr-/-WSX-1-/-) Ldlr-/- mice were generated and fed with a high-cholesterol diet to induce atherosclerosis. Roles of bone marrow-derived cells in vivo and macrophages in vitro were studied using bone marrow reconstitution by transplantation and cultured peritoneal macrophages, respectively. We demonstrate that mice lacking IL-27 or IL-27 receptor are more susceptible to atherosclerosis compared with wild type due to enhanced accumulation and activation of macrophages in arterial walls. The number of circulating proinflammatory Ly6C(hi) monocytes showed no significant difference between wild-type mice and mice lacking IL-27 or IL-27 receptor. Administration of IL-27 suppressed the development of atherosclerosis in vivo and macrophage activation in vitro that was indicated by increased uptake of modified low-density lipoprotein and augmented production of proinflammatory cytokines. These findings define a novel inhibitory role for IL-27 in atherosclerosis that regulates macrophage activation in mice. PMID:23729211

  6. Author's personal copy Atherosclerosis 211 (2010) 445450

    E-print Network

    Daraio, Chiara

    2010-01-01

    Author's personal copy Atherosclerosis 211 (2010) 445­450 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Choosing the optimal wall shear of these parameters in patients' vessels before the onset of atherosclerosis to the specific plaque sites thereafter

  7. CD8{sup +}CD25{sup +} T cells reduce atherosclerosis in apoE(?/?) mice

    SciTech Connect

    Zhou, Jianchang; Dimayuga, Paul C.; Zhao, Xiaoning; Yano, Juliana; Lio, Wai Man; Trinidad, Portia; Honjo, Tomoyuki; Cercek, Bojan; Shah, Prediman K.; Chyu, Kuang-Yuh

    2014-01-17

    Highlights: •The role of a sub-population of CD8{sup +} T cells with suppressor functions was investigated in atherosclerosis. •CD8{sup +}CD25{sup +} T cells from adult apoE(?/?) mice had phenotype characteristics of T suppressor cells. •These CD8{sup +}CD25{sup +} T cells reduced CD4{sup +} T cell proliferation and CD8{sup +} cytotoxic activity in vitro. •Adoptive transfer of CD8{sup +}CD25{sup +} T cells significantly reduced atherosclerosis. •CD8{sup +}CD25{sup +} T cells have a suppressive function in atherosclerosis. -- Abstract: Background: It is increasingly evident that CD8{sup +} T cells are involved in atherosclerosis but the specific subtypes have yet to be defined. CD8{sup +}CD25{sup +} T cells exert suppressive effects on immune signaling and modulate experimental autoimmune disorders but their role in atherosclerosis remains to be determined. The phenotype and functional role of CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis were investigated in this study. Methods and results: CD8{sup +}CD25{sup +} T cells were observed in atherosclerotic plaques of apoE(?/?) mice fed hypercholesterolemic diet. Characterization by flow cytometric analysis and functional evaluation using a CFSE-based proliferation assays revealed a suppressive phenotype and function of splenic CD8{sup +}CD25{sup +} T cells from apoE(?/?) mice. Depletion of CD8{sup +}CD25{sup +} from total CD8{sup +} T cells rendered higher cytolytic activity of the remaining CD8{sup +}CD25{sup ?} T cells. Adoptive transfer of CD8{sup +}CD25{sup +} T cells into apoE(?/?) mice suppressed the proliferation of splenic CD4{sup +} T cells and significantly reduced atherosclerosis in recipient mice. Conclusions: Our study has identified an athero-protective role for CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis.

  8. Blood Pressure Response to Zofenopril or Irbesartan Each Combined with Hydrochlorothiazide in High-Risk Hypertensives Uncontrolled by Monotherapy: A Randomized, Double-Blind, Controlled, Parallel Group, Noninferiority Trial

    PubMed Central

    Malacco, Ettore; Omboni, Stefano; Parati, Gianfranco

    2015-01-01

    In this randomized, double-blind, controlled, parallel group study (ZENITH), 434 essential hypertensives with additional cardiovascular risk factors, uncontrolled by a previous monotherapy, were treated for 18 weeks with zofenopril 30 or 60?mg plus hydrochlorothiazide (HCTZ) 12.5?mg or irbesartan 150 or 300?mg plus HCTZ. Rate of office blood pressure (BP) response (zofenopril: 68% versus irbesartan: 70%; p = 0.778) and 24-hour BP response (zofenopril: 85% versus irbesartan: 84%; p = 0.781) was similar between the two treatment groups. Cardiac and renal damage was equally reduced by both treatments, whereas the rate of carotid plaque regression was significantly larger with zofenopril. In conclusion, uncontrolled monotherapy treated hypertensives effectively respond to a combination of zofenopril or irbesartan plus a thiazide diuretic, in terms of either BP response or target organ damage progression. PMID:26347187

  9. How Can Atherosclerosis Be Prevented or Delayed?

    MedlinePLUS

    ... page from the NHLBI on Twitter. How Can Atherosclerosis Be Prevented or Delayed? Taking action to control ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  10. Scavenger Receptors, Oxidized LDL, and Atherosclerosis

    E-print Network

    Dennis, Edward A.

    214 Scavenger Receptors, Oxidized LDL, and Atherosclerosis AGNES BOULLIER, DAVID A. BIRD, MI receptors; oxidized LDL; atherosclerosis; apoptotic cells INTRODUCTION Most of the lipid-laden "foam cells-534- 2005. dsteinberg@ucsd.edu #12;215BOULLIER et al.: SCAVENGER RECEPTORS, LDL, AND ATHEROSCLEROSIS

  11. Vitamin K Intake and Atherosclerosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been hypothesized that insufficient intake of vitamin K may increase soft tissue calcification due to impaired gamma-carboxylation of the vitamin K-dependent protein, matrix gamma-carboxyglutamic acid (MGP). The evidence to support this putative role of vitamin K intake in atherosclerosis is ...

  12. Mitochondrial DNA damage and atherosclerosis

    E-print Network

    Yu, E. P. K.; Bennett, M. R.

    2014-01-01

    Mitochondria generate ATP using substrates from the Krebs cycle that can be 315 derived from lipids, carbohydrates and proteins. Mitochondria therefore coordinate 316 metabolism and energy production, with energy levels signalled by the AMP/ATP 317 ratio... inflammation is an important link between mtDNA damage, dysfunction and 201 atherosclerosis, oxidative stress may also mediate the effects of mtDNA defects. As 202 suggested in the mitochondrial/free-radical theory of ageing, a vicious cycle can exist 203...

  13. Immunity, atherosclerosis and cardiovascular disease

    PubMed Central

    2013-01-01

    Atherosclerosis, the major cause of cardiovascular disease (CVD), is a chronic inflammatory condition with immune competent cells in lesions producing mainly pro-inflammatory cytokines. Dead cells and oxidized forms of low density lipoproteins (oxLDL) are abundant. The major direct cause of CVD appears to be rupture of atherosclerotic plaques. oxLDL has proinflammatory and immune-stimulatory properties, causes cell death at higher concentrations and contains inflammatory phospholipids with phosphorylcholine (PC) as an interesting epitope. Antibodies against PC (anti-PC) may be atheroprotective, one mechanism being anti-inflammatory. Bacteria and virus have been discussed, but it has been difficult to find direct evidence, and antibiotic trials have not been successful. Heat shock proteins could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include pro-inflammatory cytokines, chemokines, and lipid mediators. To prove that inflammation is a cause of atherosclerosis and CVD, clinical studies with anti-inflammatory and/or immune-modulatory treatment are needed. The potential causes of immune reactions and inflammation in atherosclerosis and how inflammation can be targeted therapeutically to provide novel treatments for CVD are reviewed. PMID:23635324

  14. Atherosclerosis in juvenile idiopathic arthritis.

    PubMed

    Jednacz, Ewa; Rutkowska-Sak, Lidia

    2012-01-01

    Atherosclerosis is a chronic inflammatory disease of the arteries. Clinical consequences of the atherosclerotic process occur in the adult population, however atherosclerotic process begins in childhood. The classic risk factors for atherosclerosis include obesity, dyslipidaemia, age, gender or family history. In recent years, attention has been drawn to the similarity between atherosclerotic inflammatory processes and inflammatory changes in the course of systemic connective tissue disease, in particular systemic lupus etythematosus (SLE) or rheumatoid arthritis (RA). There is also observed the similarity of the pathogenetic background of development of atherosclerosis and juvenile idiopathic arthritis (JIA). Elevated levels of pro-inflammatory cytokines are observed in the course of juvenile idiopathic arthritis. Also homocysteine concentrations, which may play a significant role in the development of atherosclerotic lesions, are observed higher in patients with JIA. Some studies revealed higher carotid intima-media thickness (IMT) index values in children with JIA. In view of the fact that atherosclerotic process begins as early as in childhood, the introduction of appropriate preventive measures in children is a matter of utmost importance. PMID:22933832

  15. Sex Differences in Inflammation During Atherosclerosis

    PubMed Central

    Fairweather, DeLisa

    2014-01-01

    Atherosclerosis is the leading cause of death in the United States and worldwide, yet more men die from atherosclerosis than women, and at a younger age. Women, on the other hand, mainly develop atherosclerosis following menopause, and particularly if they have one or more autoimmune diseases, suggesting that the immune mechanisms that increase disease in men are different from those in women. The key processes in the pathogenesis of atherosclerosis are vascular inflammation, lipid accumulation, intimal thickening and fibrosis, remodeling, and plaque rupture or erosion leading to myocardial infarction and ischemia. Evidence indicates that sex hormones alter the immune response during atherosclerosis, resulting in different disease phenotypes according to sex. Women, for example, respond to infection and damage with increased antibody and autoantibody responses, while men have elevated innate immune activation. This review describes current knowledge regarding sex differences in the inflammatory immune response during atherosclerosis. Understanding sex differences is critical for improving individualized medicine. PMID:25983559

  16. A multimodal Darwinian strategy for alleviating the atherosclerosis pandemic.

    PubMed

    Mathew, Geetha; Thambi, Magith; Unnikrishnan, M K

    2014-02-01

    The conflict between our 'primitive' genes and 'modern' lifestyle probably lies at the root of several disorders that afflict modern man. Atherosclerosis, which is relatively unknown among contemporary hunter-gatherer populations, has reached pandemic proportions in recent times. Being an evolutionary problem with several inter-related pathologies, current therapeutic strategy for treating atherosclerosis has inherent limitations. Reviewing evolution-linked risk factors suggests that there are four aspects to the etiology of atherosclerosis namely, decreased intestinal parasitism, oversensitivity of evolutionarily redundant mast cells, chronic underactivation of AMPK (cellular energy sensor) and a deficiency of vitamin D. A combination of these four causes appear to have precipitated the atherosclerosis pandemic in modern times. Man and worms co-existed symbiotically in the past. Massive de-worming campaigns could have disrupted this symbiosis, increasing nutritional availability to man (pro-obesity) at the cost of decreased immunotolerance (pro-atherogenicity). A reduction in helminth-induced chronic TH2 activation could also have enhanced TH1 polarization, eventually disrupting the reciprocal regulation of TH1/TH2 balance and resulting in atherosclerosis. The riddance of helminth infestations may have rendered mast cells immunologically redundant, making them oversensitive to inflammatory stimuli, thereby playing a pro-atherogenic role. AMPK activation exerts pleiotropic anti-atherogenic effects, such as suppression of fatty acid, cholesterol, protein synthesis, reduction of vascular smooth muscle proliferation, etc. As energy deficit is the chief stimulus for AMPK activation, the over-nourished modern man appears to be suffering from chronic underactivation of AMPK, legitimising the unrivalled supremacy of metformin, the oldest prescribed antidiabetic drug. The fact that humans evolved in the sunny tropics suggests that humans are selected for high vitamin D levels. Vitamin D deficiency is now linked to several conditions including increased risk of CV disorders, diabetes, etc. The manifold decrease in vitamin D levels in modern man justifies a need for supplementation. We therefore hypothesize that a judicious combination of mast cell stabilization, AMPK activation, vitamin D supplementation, and moderation in hygiene practices could be an evolution-based multimodal strategy for both preventing and mitigating the pandemic of atherosclerosis. PMID:24355423

  17. Multi-Ethnic Study of Atherosclerosis (MESA)

    ClinicalTrials.gov

    2015-06-02

    Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Coronary Artery Disease; Coronary Disease; Stroke; Myocardial Infarction; Heart Failure; Diabetes Mellitus, Type 2; Hypertension; Diabetes Mellitus

  18. What Are the Signs and Symptoms of Atherosclerosis?

    MedlinePLUS

    ... Twitter. What Are the Signs and Symptoms of Atherosclerosis? Atherosclerosis usually doesn't cause signs and symptoms ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  19. Oxyradical Stress, Endocannabinoids, and Atherosclerosis

    PubMed Central

    Matthews, Anberitha T.; Ross, Matthew K.

    2015-01-01

    Atherosclerosis is responsible for most cardiovascular disease (CVD) and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation. Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression. Overactive NADPH oxidase (Nox) produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis. Although superoxide and reactive oxygen species (ROS) have obvious toxic properties, they also have fundamental roles in signaling pathways that enable cells to adapt to stress. In addition to inflammation and ROS, the endocannabinoid system (eCB) is also important in atherogenesis. Linkages have been postulated between the eCB system, Nox, oxidative stress, and atherosclerosis. For instance, CB2 receptor-evoked signaling has been shown to upregulate anti-inflammatory and anti-oxidative pathways, whereas CB1 signaling appears to induce opposite effects. The second messenger lipid molecule diacylglycerol is implicated in the regulation of Nox activity and diacylglycerol lipase ? (DAGL?) is a key biosynthetic enzyme in the biosynthesis eCB ligand 2-arachidonylglycerol (2-AG). Furthermore, Nrf2 is a vital transcription factor that protects against the cytotoxic effects of both oxidant and electrophile stress. This review will highlight the role of reactive oxygen species (ROS) in intracellular signaling and the impact of deregulated ROS-mediated signaling in atherogenesis. In addition, there is also emerging knowledge that the eCB system has an important role in atherogenesis. We will attempt to integrate oxidative stress and the eCB system into a conceptual framework that provides insights into this pathology. PMID:26702404

  20. ABC transporters, atherosclerosis and inflammation.

    PubMed

    Fitzgerald, Michael L; Mujawar, Zahedi; Tamehiro, Norimasa

    2010-08-01

    Atherosclerosis, driven by inflamed lipid-laden lesions, can occlude the coronary arteries and lead to myocardial infarction. This chronic disease is a major and expensive health burden. However, the body is able to mobilize and excrete cholesterol and other lipids, thus preventing atherosclerosis by a process termed reverse cholesterol transport (RCT). Insight into the mechanism of RCT has been gained by the study of two rare syndromes caused by the mutation of ABC transporter loci. In Tangier disease, loss of ABCA1 prevents cells from exporting cholesterol and phospholipid, thus resulting in the build-up of cholesterol in the peripheral tissues and a loss of circulating HDL. Consistent with HDL being an athero-protective particle, Tangier patients are more prone to develop atherosclerosis. Likewise, sitosterolemia is another inherited syndrome associated with premature atherosclerosis. Here mutations in either the ABCG5 or G8 loci, prevents hepatocytes and enterocytes from excreting cholesterol and plant sterols, including sitosterol, into the bile and intestinal lumen. Thus, ABCG5 and G8, which from a heterodimer, constitute a transporter that excretes cholesterol and dietary sterols back into the gut, while ABCA1 functions to export excess cell cholesterol and phospholipid during the biogenesis of HDL. Interestingly, a third protein, ABCG1, that has been shown to have anti-atherosclerotic activity in mice, may also act to transfer cholesterol to mature HDL particles. Here we review the relationship between the lipid transport activities of these proteins and their anti-atherosclerotic effect, particularly how they may reduce inflammatory signaling pathways. Of particular interest are recent reports that indicate both ABCA1 and ABCG1 modulate cell surface cholesterol levels and inhibit its partitioning into lipid rafts. Given lipid rafts may provide platforms for innate immune receptors to respond to inflammatory signals, it follows that loss of ABCA1 and ABCG1 by increasing raft content will increase signaling through these receptors, as has been experimentally demonstrated. Moreover, additional reports indicate ABCA1, and possibly SR-BI, another HDL receptor, may directly act as anti-inflammatory receptors independent of their lipid transport activities. Finally, we give an update on the progress and pitfalls of therapeutic approaches that seek to stimulate the flux of lipids through the RCT pathway. PMID:20138281

  1. Endothelium Preserving Microwave Treatment for Atherosclerosis

    NASA Technical Reports Server (NTRS)

    Fink, Patrick; Arndt, G. D.; Ngo, Phong

    2003-01-01

    This slide presentation reviews the use of microwave technology for treating Atherosclerosis while preserving the endothelium. The system uses catheter antennas as part of the system that is intended to treat atherosclerosis. The concept is to use a microwave catheter for heating the atherosclerotic lesions, and reduce constriction in the artery.

  2. Vasa Vasorum in Atherosclerosis and Clinical Significance

    PubMed Central

    Xu, Junyan; Lu, Xiaotong; Shi, Guo-Ping

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease that leads to several acute cardiovascular complications with poor prognosis. For decades, the role of the adventitial vasa vasorum (VV) in the initiation and progression of atherosclerosis has received broad attention. The presence of VV neovascularization precedes the apparent symptoms of clinical atherosclerosis. VV also mediates inflammatory cell infiltration, intimal thickening, intraplaque hemorrhage, and subsequent atherothrombosis that results in stroke or myocardial infarction. Intraplaque neovessels originating from VV can be immature and hence susceptible to leakage, and are thus regarded as the leading cause of intraplaque hemorrhage. Evidence supports VV as a new surrogate target of atherosclerosis evaluation and treatment. This review provides an overview into the relationship between VV and atherosclerosis, including the anatomy and function of VV, the stimuli of VV neovascularization, and the available underlying mechanisms that lead to poor prognosis. We also summarize translational researches on VV imaging modalities and potential therapies that target VV neovascularization or its stimuli. PMID:26006236

  3. Quantification of carotid vessel atherosclerosis

    NASA Astrophysics Data System (ADS)

    Chiu, Bernard; Egger, Micaela; Spence, J. D.; Parraga, Grace; Fenster, Aaron

    2006-03-01

    Atherosclerosis is characterized by the development of plaques in the arterial wall, which ultimately leads to heart attacks and stroke. 3D ultrasound (US) has been used to screen patients' carotid arteries. Plaque measurements obtained from these images may aid in the management and monitoring of patients, and in evaluating the effect of new treatment options. Different types of measures for ultrasound phenotypes of atherosclerosis have been proposed. Here, we report on the development and application of a method used to analyze changes in carotid plaque morphology from 3D US images obtained at two different time points. We evaluated our technique using manual segmentations of the wall and lumen of the carotid artery from images acquired in two US scanning sessions. To incorporate the effect of intraobserver variability in our evaluation, manual segmentation was performed five times each for the arterial wall and lumen. From this set of five segmentations, the mean wall and lumen surfaces were reconstructed, with the standard deviation at each point mapped onto the surfaces. A correspondence map between the mean wall and lumen surfaces was then established, and the thickness of the atherosclerotic plaque at each point in the vessel was estimated to be the distance between each correspondence pairs. The two-sample Student's t-test was used to judge whether the difference between the thickness values at each pair corresponding points of the arteries in the two 3D US images was statistically significant.

  4. The autoimmune concept of atherosclerosis

    PubMed Central

    Grundtman, Cecilia; Wick, Georg

    2011-01-01

    Purpose of review This review summarizes the recent data on the ‘Autoimmune Concept of Atherosclerosis’, according to which the first stage of this disease is due to an autoimmune reaction against arterial endothelial cells expressing heat shock protein 60 (HSP60) and adhesion molecules when stressed by classical atherosclerosis risk factors. Special emphasis is put on oxidized low-density lipoproteins as early endothelial stressors. Recent findings Plasma cholesterol and LDL levels considered ‘normal’ by the medical community are possibly too high from an evolutionary viewpoint. The proinflammatory milieu at sites of early atherosclerotic lesions could be conducive to oxidation of LDL in situ. LDL oxidation can also take place at nonvascular sites or in the circulation under general proinflammatory conditions explaining its proatherosclerotic role in ‘normocholesterolemic’ individuals. Summary We hypothesize that the plasma cholesterol and LDL levels currently considered normal are evolutionarily too high. Cholesterol and/or oxidized low-density lipoprotein, even as a mild HSP60-inducing endothelial stressor, function as a ubiquitous risk factor. If this hypothesis is true, most members of developed societies might be at risk to develop atherosclerotic plaques at anti-HSP60-immunity-triggered intimal inflammatory foci, irrespective of the primary risk-factor(s). PMID:21881502

  5. Atherosclerosis

    MedlinePLUS

    ... disease in which plaque builds up inside your arteries. Plaque is a sticky substance made up of ... blood. Over time, plaque hardens and narrows your arteries. That limits the flow of oxygen-rich blood ...

  6. Atherosclerosis

    MedlinePLUS

    ... hardens and narrows your arteries. This limits the flow of oxygen-rich blood to your organs and other parts ... your neck (the carotid arteries). These arteries supply oxygen-rich blood to your brain. If blood flow to your brain is reduced or blocked, you ...

  7. Atherosclerosis

    MedlinePLUS

    ... for heart health as EPA and DHA. Red yeast rice. A common seasoning in Asian countries, red yeast rice may help reduce the amount of cholesterol ... supplement. Talk to your doctor before taking red yeast rice, especially if you take another cholesterol-lowering ...

  8. Platelets and the complement cascade in atherosclerosis

    PubMed Central

    Patzelt, Johannes; Verschoor, Admar; Langer, Harald F.

    2015-01-01

    Atherosclerosis and its late sequels are still the number one cause of death in western societies. Platelets are a driving force not only during the genesis of atherosclerosis, but especially in its late stages, as evidenced by complications such as arterial thrombosis, myocardial infarction, and ischemic stroke. Atherosclerosis is increasingly recognized as an inflammatory disease, influenced by various immune mechanisms. The complement system is part of our innate immune system, and its diverse roles in atherosclerosis have become evident over the past years. In this review we identify points of intersection between platelets and the complement system and discuss their relevance for atherosclerosis. Specifically, we will focus on roles for platelets in the onset as well as progression of the disease, a possible dual role for complement in the genesis and development of atherosclerosis, and review emerging literature revealing previously unrecognized cross-talk between platelets and the complement system and discuss its possible impact for atherosclerosis. Finally, we identify limitations of current research approaches and discuss perspectives of complement modulation in the control of the disease. PMID:25784879

  9. History of Discovery: Inflammation in Atherosclerosis

    PubMed Central

    Libby, Peter

    2012-01-01

    Experimental work has elucidated molecular and cellular pathways of inflammation that promote atherosclerosis. Unraveling the roles of cytokines as inflammatory messengers provided a mechanism whereby risk factors for atherosclerosis can alter arterial biology, and produce a systemic milieu that favors atherothrombotic events. The discovery of the immune basis of allograft arteriosclerosis demonstrated that inflammation per se can drive arterial hyperplasia, even in the absence of traditional risk factors. Inflammation regulates aspects of plaque biology that trigger the thrombotic complications of atherosclerosis. Translation of these discoveries to humans has enabled both novel mechanistic insights and practical clinical advances. PMID:22895665

  10. Methylarginines in Mice with Experimental Atherosclerosis.

    PubMed

    Gilinsky, M A; Sukhovershin, R A; Cherkanova, M S

    2015-11-01

    We studied the dynamics of indexes for the system of endogenous regulation of NO bioavailability. The content of NO synthase inhibitors (monomethylarginine and asymmetric dimethylarginine) in the blood of mice was measured after intraperitoneal injections of a nonionic surfactant poloxamer 407 for 2 and 14 weeks. The concentrations of both methylarginines in animals with atherosclerosis due to 14-week administration of poloxamer were much higher than in control specimens. The amount of arginine and symmetric dimethylarginine practically did not differ from the control. Poloxamer-induced model of atherosclerosis is characterized by increased content of NO synthase inhibitors. These changes contribute to the development of endothelial dysfunction and atherosclerosis. PMID:26601840

  11. Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis

    PubMed Central

    Miao, Ji; Ling, Alisha V.; Manthena, Praveen V.; Gearing, Mary E.; Graham, Mark J.; Crooke, Rosanne M.; Croce, Kevin J.; Esquejo, Ryan M.; Clish, Clary B.; Torrecilla, Esther; Vázquez, Gumersindo Fernández; Rubio, Miguel A.; Cabrerizo, Lucio; Barabash, Ana; Pernaute, Andrés Sánchez; Torres, Antonio J.; Vicent, David; Biddinger, Sudha B.

    2015-01-01

    Despite the well-documented association between insulin resistance and cardiovascular disease, the key targets of insulin relevant to the development of cardiovascular disease are not known. Here, using non-biased profiling methods, we identify the enzyme flavin-containing monooxygenase 3 (Fmo3) to be a target of insulin. FMO3 produces trimethylamine N-oxide (TMAO), which has recently been suggested to promote atherosclerosis in mice and humans. We show that FMO3 is suppressed by insulin in vitro, increased in obese/insulin resistant male mice and increased in obese/insulin-resistant humans. Knockdown of FMO3 in insulin-resistant mice suppresses FoxO1, a central node for metabolic control, and entirely prevents the development of hyperglycaemia, hyperlipidemia and atherosclerosis. Taken together, these data indicate that FMO3 is required for FoxO1 expression and the development of metabolic dysfunction. PMID:25849138

  12. Innate and Adaptive Immunity in Atherosclerosis

    PubMed Central

    Packard, René R. S.; Lichtman, Andrew H.; Libby, Peter

    2010-01-01

    Atherosclerosis, a chronic inflammatory disorder, involves both the innate and adaptive arms of the immune response that mediate the initiation, progression, and ultimate thrombotic complications of atherosclerosis. Most fatal thromboses, which may manifest as acute myocardial infarction or ischemic stroke, result from frank rupture or superficial erosion of the fibrous cap overlying the atheroma, processes that occur in inflammatorily active, rupture-prone plaques. Appreciation of the inflammatory character of atherosclerosis has led to the application of C-reactive protein as a biomarker of cardiovascular risk, and the characterization of the anti-inflammatory and immunomodulatory actions of the statin class of drugs. An improved understanding of the pathobiology of atherosclerosis and further studies of its immune mechanisms provide avenues for the development of future strategies directed toward better risk stratification of patients as well as the identification of novel anti-inflammatory therapies. This review retraces leukocyte subsets involved in innate and adaptive immunity and their contributions to atherogenesis. PMID:19449008

  13. Atherosclerosis and the internal mammary arteries

    SciTech Connect

    Singh, R.N.

    1983-06-01

    One hundred and fifty patients with coronary artery disease (CAD), 14 (9.3%) of whom had coexisting peripheral vascular disease, underwent bilateral internal mammary arteriography to study the incidence and extent of atherosclerosis in these vessels. Significant atherosclerosis of the internal mammary arteries (IMAs) was present in three patients (2%), of whom one had coexisting peripheral vascular disease. Lesions in the IMAs were found either proximally, close to the origin or distally, around the terminal bifurcation. Six of the 14 patients with peripheral vascular disease (4% of total subjects) had significant atherosclerosis of the brachiocephalic arteries. Atherosclerotic involvement of the IMA is very unusual and rarely interferes with the use of these vessels for coronary bypass. More common, however, is atherosclerosis of the subclavian arteries, a contraindication for IMA grafting if the lesion is proximal to the IMA origin.

  14. Secondary retroperitoneal fibrosis associated with generalized atherosclerosis.

    PubMed

    Barbullushi, M; Pasko, N; Bezhani, E; Duraku, A; Rusi, R; Hoti, K; Bakalli, V; Idrizi, A

    1999-01-01

    Retroperitoneal fibrosis is an uncommon disease that often presents in a subtle manner. Only a few cases of the combined association of generalized atherosclerosis and retroperitoneal fibrosis are reported in the recent literature, supporting the view that the condition is probably an autoimmune periaortitis. We describe a typical case of retroperitoneal fibrosis associated with generalized atherosclerosis with clinical presentation of progressive renal insufficiency, and claudication from arterial compromise. PMID:18212457

  15. Superoxide and peroxynitrite in atherosclerosis.

    PubMed Central

    White, C R; Brock, T A; Chang, L Y; Crapo, J; Briscoe, P; Ku, D; Bradley, W A; Gianturco, S H; Gore, J; Freeman, B A

    1994-01-01

    The role of reactive oxygen species in the vascular pathology associated with atherosclerosis was examined by testing the hypothesis that impaired vascular reactivity results from the reaction of nitric oxide (.NO) with superoxide (O2-), yielding the oxidant peroxynitrite (ONOO-). Contractility studies were performed on femoral arteries from rabbits fed a cholesterol-supplemented diet. Cholesterol feeding shifted the EC50 for acetylcholine (ACh)-induced relaxation and impaired the maximal response to ACh. We used pH-sensitive liposomes to deliver CuZn superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) to critical sites of .NO reaction with O2-. Intravenously injected liposomes (3000 units of SOD per ml) augmented ACh-induced relaxation in the cholesterol-fed group to a greater extent than in controls. Quantitative immunocytochemistry demonstrated enhanced distribution of SOD in both endothelial and vascular smooth muscle cells as well as in the extracellular matrix. SOD activity in vessel homogenates of liposome-treated rabbits was also increased. Incubation of beta very low density lipoprotein with ONOO- resulted in the rapid formation of conjugated dienes and thiobarbituric acid-reactive substances. Our results suggest that the reaction of O2- with .NO is involved in the development of atherosclerotic disease by yielding a potent mediator of lipoprotein oxidation, as well as by limiting .NO stimulation of vascular smooth muscle guanylate cyclase activity. Images PMID:8302829

  16. Nitric oxide function in atherosclerosis

    PubMed Central

    Matthys, K. E.

    1997-01-01

    Atherosclerosis is a chronic inflammatory process in the intima of conduit arteries, which disturbs the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide (NO) formed by the constitutive endothelial nitric oxide synthase (eNOS). This defect predisposes to coronary vasospasm and cardiac ischaemia, with anginal pain as the typical clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis and that it may also involve the microcirculation, in which atherosclerotic lesions do not develop. On the other hand, the inflammatory environment in atherosclerotic plaques may result in the expression of the inducible NO synthase (iNOS) isozyme. Whether the dysfunction in endothelial NO production is causal to, or the result of, atherosclerotic lesion formation is still highly debated. Most evidence supports the hypothesis that constitutive endothelial NO release protects against atherogenesis e.g. by preventing smooth muscle cell proliferation and leukocyte adhesion. Nitric oxide generated by the inducible isozyme may be beneficial by replacing the failing endothelial production but excessive release may damage the vascular wall cells, especially in combination with reactive oxygen intermediates. PMID:18472828

  17. Functionally Defective High-Density Lipoprotein and Paraoxonase: A Couple for Endothelial Dysfunction in Atherosclerosis

    PubMed Central

    Eren, Esin; Yilmaz, Necat; Aydin, Ozgur

    2013-01-01

    The endothelium is the primary target for biochemical or mechanical injuries caused by the putative risk factors of atherosclerosis. Endothelial dysfunction represents the ultimate link between atherosclerotic risk factors that promote atherosclerosis. HDL-C is thought to exert at least some parts of its antiatherogenic facilities via stimulating endothelial NO production, nearby inhibiting oxidative stress and inflammation. HDL-C is capable of opposing LDL's inductive effects and avoiding the ox-LDL's inhibition of eNOS. Paraoxonase 1 (PON1) is an HDL-associated enzyme esterase which appears to contribute to the antioxidant and antiatherosclerotic capabilities of HDL-C. “Healthy HDL,” namely the particle that contains the active Paraoxonase 1, has the power to suppress the formation of oxidized lipids. “Dysfunctional HDL,” on the contrary, has reduced Paraoxonase 1 enzyme activity and not only fails in its mission but also potentially leads to greater formation of oxidized lipids/lipoproteins to cause endothelial dysfunction. The association of HDL-C PON1 and endothelial dysfunction depends largely on the molecules with exact damaging effect on NO synthase coupling. Loss of nitric oxide bioavailability has a pivotal role in endothelial dysfunction preceding the appearance of atherosclerosis. Analyses of HDL-C and Paraoxonase1 would be more important in the diagnosis and treatment of atherosclerosis in the very near future. PMID:24222847

  18. Atherosclerosis: Process, Indicators, Risk Factors and New Hopes

    PubMed Central

    Rafieian-Kopaei, Mahmoud; Setorki, Mahbubeh; Doudi, Monir; Baradaran, Azar; Nasri, Hamid

    2014-01-01

    Background: Atherosclerosis is the major cause of morbidities and mortalities worldwide. In this study we aimed to review the mechanism of atherosclerosis and its risk factors, focusing on new findings in atherosclerosis markers and its risk factors. Furthermore, the role of antioxidants and medicinal herbs in atherosclerosis and endothelial damage has been discussed and a list of important medicinal plants effective in the treatment and prevention of hyperlipidemia and atherosclerosis is presented. Methods: The recently published papers about atherosclerosis pathogenesis and herbal medicines effective in the treatment and prevention of hyperlipidemia and atherosclerosis were searched. Results: Inflammation has a crucial role in pathogenesis of atherosclerosis. The disease is accompanied by excessive fibrosis of the intima, fatty plaques formation, proliferation of smooth muscle cells, and migration of a group of cells such as monocytes, T cells, and platelets which are formed in response to inflammation. The oxidation of low density lipoprotein (LDL) to Ox-LDL indicates the first step of atherosclerosis in cardiovascular diseases. Malondialdehyde factor shows the level of lipoperoxidation and is a sign of increased oxidative pressure and cardiovascular diseases. In special pathological conditions such as severe hypercholesterolemia, peroxynitrite concentration increases and atherosclerosis and vascular damage are intensified. Medicinal plants have shown to be capable of interacting these or other pathogenesis factors to prevent atherosclerosis. Conclusions: The pathogenesis factors involved in atherosclerosis have recently been cleared and the discovery of these factors has brought about new hopes for better prevention and treatment of atherosclerosis. PMID:25489440

  19. [The status of atherosclerosis prevention in Austria].

    PubMed

    Schoberberger, Rudolf; Bayer, Peter; Kunze, Michael

    2003-01-01

    Although atherosclerosis is today seen as presenting a distinct clinical picture, there are almost no data available about the impact this has on medical practice and about the point at which a patient is considered high-risk. As part of a larger project on the prevention of heart disease and atherosclerosis, "Aktion plus leben", 1,117 physicians were polled in a scientific survey. The study was carried out in some 100 hospitals throughout Austria, above all in departments of internal medicine, but also in neurological departments, and in a number of other units. The results showed that in fact over 90% of those questioned see atherosclerosis as a separate, treatable illness in the context of risk prevention. The most frequent methods of diagnosis were specified as ultrasound and the clarification of symptoms of coronary heart disease. Atherosclerosis prevention is initiated above all in patients with coronary heart disease, myocardial infarction and stroke, but also very frequently in those with diabetes, peripheral vascular occlusive disease, hyperlipidemia and hypertension. Of particular interest to us was the respondents' evaluation of the effect of ramipril, the angiotensin-converting enzyme (ACE) inhibitor used in the HOPE study. The majority of those questioned see a broad range of indications for this ACE inhibitor and ascribe to it a profibrinolytic, antiinflammatory and plaque-stabilising action. Although the survey sought assessment of just one particular medication as a possible treatment option, the study documents the importance of a more inclusive concept of atherosclerosis prevention. PMID:13677258

  20. Adipokines, diabetes and atherosclerosis: an inflammatory association

    PubMed Central

    Freitas Lima, Leandro C.; Braga, Valdir de Andrade; do Socorro de França Silva, Maria; Cruz, Josiane de Campos; Sousa Santos, Sérgio H.; de Oliveira Monteiro, Matheus M.; Balarini, Camille de Moura

    2015-01-01

    Cardiovascular diseases can be considered the most important cause of death in diabetic population and diabetes can in turn increase the risk of cardiovascular events. Inflammation process is currently recognized as responsible for the development and maintenance of diverse chronic diseases, including diabetes and atherosclerosis. Considering that adipose tissue is an important source of adipokines, which may present anti and proinflammatory effects, the aim of this review is to explore the role of the main adipokines in the pathophysiology of diabetes and atherosclerosis, highlighting the therapeutic options that could arise from the manipulation of these signaling pathways both in humans and in translational models. PMID:26578976

  1. Macrophages in atherosclerosis: a dynamic balance

    PubMed Central

    Moore, Kathryn; Sheedy, Frederick; Fisher, Edward

    2015-01-01

    Preface Atherosclerosis is a chronic inflammatory disease arising from an imbalance in lipid metabolism and a maladaptive immune response driven by the accumulation of cholesterol-laden macrophages in the artery wall. Through the analysis of animal models of atherosclerosis progression and regression, there is a growing understanding that the balance of macrophages in the plaque is dynamic, with both macrophage numbers and an inflammatory phenotype influencing plaque fate. Here we summarize recently identified pro- and anti-inflammatory pathways linking lipid and inflammation biology with the retention of macrophages in plaques, as well as factors with the potential to promote their egress from these sites. PMID:23995626

  2. Incorporating HDL Interaction into an ODE Model of Atherosclerosis

    E-print Network

    Rowell, Eric C.

    Incorporating HDL Interaction into an ODE Model of Atherosclerosis Diego Lopez July 23, 2015 Abstract Atherosclerosis is a cardiovascular disease characterized by the build-up of fatty plaques die each year of atherosclerosis of the heart and half of men and women over the age of forty

  3. Chronic Intermittent Hypoxia Induces Atherosclerosis Vladimir Savransky1

    E-print Network

    Terasaki, Mark

    Chronic Intermittent Hypoxia Induces Atherosclerosis Vladimir Savransky1 , Ashika Nanayakkara1, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has atherosclerosis in C57BL/6J mice. Methods: Forty male C57BL/6J mice, 8 weeks of age, were fed either a high

  4. Phosphatidylethanolamine binding protein 1 in vacular endothelial cell autophagy and atherosclerosis

    PubMed Central

    Wang, Li; Li, HaiYing; Zhang, JinFeng; Lu, Wei; Zhao, Jing; Su, Le; Zhao, BaoXiang; Zhang, Yun; Zhang, ShangLi; Miao, JunYing

    2013-01-01

    We previously found that phosphatidylcholine-specific phospholipase C (PC-PLC) was a key inducing element of atherosclerosis, and might negatively regulate human umbilical vein endothelial cell (HUVEC) autophagy. To further investigate the mechanism of PC-PLC action, we initially identified phosphatidylethanolamine binding protein 1 (PEBP1) as a binding partner of PC-PLC by using mass spectrometry (MS, MALDI-TOF/TOF). We found that PEBP1 positively regulated PC-PLC activity in HUVECs, and inhibition of PC-PLC by its inhibitor D609 suppressed PEBP1 expression dramatically. Moreover, both PC-PLC and PEBP1 negatively regulated HUVEC autophagy independently of mammalian target of rapamycin (mTOR). Furthermore, the PEBP1 level was elevated during the development of atherosclerosis, while D609 significantly decreased the upregulated PEBP1 level in apoE?/? mice. PMID:23959677

  5. Self-eating in the Plaque: What Macrophage Autophagy Reveals About Atherosclerosis

    PubMed Central

    Sergin, Ismail; Razani, Babak

    2014-01-01

    Autophagy (or “self-eating”) is the process by which cellular contents are recycled to support downstream metabolism. An explosion in research in the past decade has implicated its role in both health and disease and established the importance of the autophagic response during periods of stress and nutrient deprivation. Atherosclerosis is a state where chronic exposure to cellular stressors promotes disease progression and alterations in autophagy is predicted to be consequential. Recent reports linking macrophage autophagy to lipid metabolism, blunted inflammatory signaling, and an overall suppression of proatherogenic processes support this notion. We review this data and provide a framework for understanding the role of macrophage autophagy in the pathogenesis of atherosclerosis, one of the most formidable diseases of our time. PMID:24746519

  6. Innervation of the arterial wall and its modification in atherosclerosis.

    PubMed

    Chistiakov, Dmitry A; Ashwell, Kenneth W; Orekhov, Alexander N; Bobryshev, Yuri V

    2015-12-01

    The autonomic nervous system (ANS) plays an essential role in the regulation of vascular tone. Sympathetic neurotransmitters epinephrine and norepinephrine are released from the terminals of perivascular nerves and suppress endothelial production of nitric oxide (NO), an important vasodilator. Sympathetic nerves also release neuropeptide Y, a co-transmitter that stimulates vasoconstriction and proliferation of vascular smooth muscle cells. Parasympathetic nerves release acetylcholine, which leads to vascular contraction when NO production is inhibited. The ANS produces a variety of other vasoactive substances including ATP, calcitonin gene-related peptide, dopamine, and serotonin. On the other hand, the vascular system can reciprocally influence ANS activity through the release of NO, reactive oxygen species (ROS), angiotensin II, and other mechanisms. In pathological conditions such as atherosclerosis, hyperactivation of sympathetic neural activity has pro-atherogenic effects on the vascular function by increasing vasoconstriction, accumulation of modified lipoproteins in the vascular wall, induction of endothelial dysfunction, and stimulation of oxidative stress and vascular remodeling. Indeed, suppression of the sympathetic ANS should be beneficial for the treatment of cardiovascular diseases. PMID:26164815

  7. Interferon-?: Promising therapeutic target in atherosclerosis

    PubMed Central

    Moss, Joe WE; Ramji, Dipak P

    2015-01-01

    Atherosclerosis is a chronic inflammatory disorder of the vasculature and is the primary cause of cardiovascular disease (CVD). CVD is currently the world’s leading cause of death and the numbers are predicted to rise further because of a global increase in risk factors such as diabetes and obesity. Current therapies such as statins have had a major impact in reducing mortality from CVD. However, there is a marked residual CVD risk in patients on statin therapy. It is therefore important to understand the molecular basis of this disease in detail and to develop alternative novel therapeutics. Interferon-? (IFN-?) is a pro-inflammatory cytokine that is often regarded as a master regulator of atherosclerosis development. IFN-? is able to influence several key steps during atherosclerosis development, including pro-inflammatory gene expression, the recruitment of monocytes from the blood to the activated arterial endothelium and plaque stability. This central role of IFN-? makes it a promising therapeutic target. The purpose of this editorial is to describe the key role IFN-? plays during atherosclerosis development, as well as discuss potential strategies to target it therapeutically. PMID:26309816

  8. Immune and Inflammatory Mechanisms of Atherosclerosis*

    PubMed Central

    Galkina, Elena; Ley, Klaus

    2009-01-01

    Atherosclerosis is an inflammatory disease of the wall of large- and medium-sized arteries that is precipitated by elevated levels of low-density lipoprotein (LDL) cholesterol in the blood. Although dendritic cells (DCs) and lymphocytes are found in the adventitia of normal arteries, their number is greatly expanded and their distribution changed in human and mouse atherosclerotic arteries. Macrophages, DCs, foam cells, lymphocytes, and other inflammatory cells are found in the intimal atherosclerotic lesions. Beneath these lesions, adventitial leukocytes organize in clusters that resemble tertiary lymphoid tissues. Experimental interventions can reduce the number of available blood monocytes, from which macrophages and most DCs and foam cells are derived, and reduce atherosclerotic lesion burden without altering blood lipids. Under proatherogenic conditions, nitric oxide production from endothelial cells is reduced and the burden of reactive oxygen species (ROS) and advanced glycation end products (AGE) is increased. Incapacitating ROS-generating NADPH oxidase or the receptor for AGE (RAGE) has beneficial effects. Targeting inflammatory adhesion molecules also reduces atherosclerosis. Conversely, removing or blocking IL-10 or TGF-? accelerates atherosclerosis. Regulatory T cells and B1 cells secreting natural antibodies are atheroprotective. This review summarizes our current understanding of inflammatory and immune mechanisms in atherosclerosis. PMID:19302038

  9. ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY (ARIC)

    EPA Science Inventory

    Epidemiology Study -- ARIC is a large-scale, long-term prospective study that measures associations of established and suspected coronary heart disease risk factors with both atherosclerosis and new CHD events in men and women from four geographically diverse communities. The pro...

  10. New insights into immunological aspects of atherosclerosis.

    PubMed

    Jawie?, Jacek

    2008-03-01

    Although atherosclerosis was previously thought to be mainly a degenerative disease, it is now well ascertained that its pathogenesis is inflammatory. This review describes the history of a new atherogenetic concept, including the pivotal role of apoE-knockout mice in understanding the inflammatory background of atherosclerosis. There has been lack of unequivocal evidence of an important inflammatory component in atherogenesis. This evidence was delivered by a new technique--gene targeting, for the invention of which Mario R. Capecchi, Martin J. Evans and Oliver Smithies received in 2007 the Nobel Prize in Physiology or Medicine. The pivotal stage of atherogenesis is the antigen presentation by macrophages to T lymphocytes. This antigen could be a fragment of oxidized low-density lipoproteins "digested" by macrophage, heat shock protein 60, beta2-glycoprotein I or fragments of bacterial antigens. For interaction between the immunological cells a presence of CD40 receptor on macrophages and its ligand CD40L on the surface of T lymphocytes are necessary. During the interaction between these cells an immunological type T helper 1 (Th1--cellular) or T helper 2 (Th2--humoral) response arises. Th1 response and its mediators: interferon gamma, tumor necrosis factor alpha, interleukin-1, interleukin-12 and interleukin-18 enhance atherogenesis, whereas Th2 response and its mediators: interleukin-4, interleukin-5, interleukin-10 and interleukin-13 inhibit the development of atherosclerosis. Atherosclerosis is therefore a chronic inflammatory disease, in most cases initiated by hypercholesterolemia. Nowadays, hypercholesterolemia and inflammation are considered as "partners in crime". The concept of atherosclerosis as inflammatory disease is fairly new, however, it is already considered as an undisputable achievement of science which have particular therapeutic consequences. PMID:18476459

  11. ATP-Binding Cassette Transporters and HDL Suppress Hematopoietic Stem Cell Proliferation

    PubMed Central

    Yvan-Charvet, Laurent; Pagler, Tamara; Gautier, Emmanuel L.; Avagyan, Serine; Siry, Read L.; Han, Seongah; Welch, Carrie L.; Wang, Nan; Randolph, Gwendalyn J.; Snoeck, Hans W.; Tall, Alan R.

    2011-01-01

    Elevated leukocyte cell numbers (leukocytosis), and monocytes in particular, promote atherosclerosis; however, how they become increased is poorly understood. Mice deficient in the adenosine triphosphate–binding cassette (ABC) transporters ABCA1 and ABCG1, which promote cholesterol efflux from macrophages and suppress atherosclerosis in hypercholesterolemic mice, displayed leukocytosis, a transplantable myeloproliferative disorder, and a dramatic expansion of the stem and progenitor cell population containing Lin? Sca-1+Kit+ (LSK) in the bone marrow. Transplantation of Abca1?/? Abcg1?/? bone marrow into apolipoprotein A-1 transgenic mice with elevated levels of high-density lipoprotein (HDL) suppressed the LSK population, reduced leukocytosis, reversed the myeloproliferative disorder, and accelerated atherosclerosis. The findings indicate that ABCA1, ABCG1, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis. PMID:20488992

  12. ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation.

    PubMed

    Yvan-Charvet, Laurent; Pagler, Tamara; Gautier, Emmanuel L; Avagyan, Serine; Siry, Read L; Han, Seongah; Welch, Carrie L; Wang, Nan; Randolph, Gwendalyn J; Snoeck, Hans W; Tall, Alan R

    2010-06-25

    Elevated leukocyte cell numbers (leukocytosis), and monocytes in particular, promote atherosclerosis; however, how they become increased is poorly understood. Mice deficient in the adenosine triphosphate-binding cassette (ABC) transporters ABCA1 and ABCG1, which promote cholesterol efflux from macrophages and suppress atherosclerosis in hypercholesterolemic mice, displayed leukocytosis, a transplantable myeloproliferative disorder, and a dramatic expansion of the stem and progenitor cell population containing Lin(-)Sca-1(+)Kit+ (LSK) in the bone marrow. Transplantation of Abca1(-/-) Abcg1(-/-) bone marrow into apolipoprotein A-1 transgenic mice with elevated levels of high-density lipoprotein (HDL) suppressed the LSK population, reduced leukocytosis, reversed the myeloproliferative disorder, and accelerated atherosclerosis. The findings indicate that ABCA1, ABCG1, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis. PMID:20488992

  13. VASCULAR INFLAMMATION AND ATHEROGENESIS ARE ACTIVATED VIA RECEPTORS FOR PAMPs AND SUPPRESSED BY REGULATORY T CELLS

    PubMed Central

    Yang, Xiao-Feng; Yin, Ying; Wang, Hong

    2009-01-01

    Despite significant advances in identifying the risk factors and elucidating atherosclerotic pathology, atherosclerosis remains the leading cause of morbidity and mortality in industrialized society. These risk factors independently or synergistically lead to chronic vascular inflammation, which is an essential requirement for the progression of atherosclerosis in patients. However, the mechanisms underlying the pathogenic link between the risk factors and atherosclerotic inflammation remain poorly defined. Significant progress has been made in two major areas, which are determination of the roles of the receptors for pathogen-associated molecular patterns (PAMPs) in initiation of vascular inflammation and atherosclerosis, and characterization of the roles of regulatory T cells in suppression of vascular inflammation and atherosclerosis. In this review, we focus on three related issues: (1) examining the recent progress in endothelial cell pathology, inflammation and their roles in atherosclerosis; (2) analyzing the roles of the receptors for pathogen-associated molecular patterns (PAMPs) in initiation of vascular inflammation and atherosclerosis; and (3) analyzing the advances in our understanding of suppression of vascular inflammation and atherosclerosis by regulatory T cells. Continuous improvement of our understanding of the risk factors involved in initiation and promotion of artherogenesis, will lead to the development of novel therapeutics for ischemic stroke and cardiovascular diseases. PMID:19578482

  14. Lipoprotein lipase: from gene to atherosclerosis.

    PubMed

    Li, Yuan; He, Ping-Ping; Zhang, Da-Wei; Zheng, Xi-Long; Cayabyab, Fracisco S; Yin, Wei-Dong; Tang, Chao-Ke

    2014-12-01

    Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and responsible for catalyzing lipolysis of triglycerides in lipoproteins. LPL is produced mainly in adipose tissue, skeletal and heart muscle, as well as in macrophage and other tissues. After synthesized, it is secreted and translocated to the vascular lumen. LPL expression and activity are regulated by a variety of factors, such as transcription factors, interactive proteins and nutritional state through complicated mechanisms. LPL with different distributions may exert distinct functions and have diverse roles in human health and disease with close association with atherosclerosis. It may pose a pro-atherogenic or an anti-atherogenic effect depending on its locations. In this review, we will discuss its gene, protein, synthesis, transportation and biological functions, and then focus on its regulation and relationship with atherosclerosis and potential underlying mechanisms. The goal of this review is to provide basic information and novel insight for further studies and therapeutic targets. PMID:25463094

  15. A systems biology approach to understanding atherosclerosis

    PubMed Central

    Ramsey, Stephen A; Gold, Elizabeth S; Aderem, Alan

    2010-01-01

    Atherosclerosis, a chronic inflammatory disease of the vascular system, presents significant challenges to developing effective molecular diagnostics and novel therapies. A systems biology approach integrating data from large-scale measurements (e.g. transcriptomics, proteomics and genomics) is successfully contributing to deciphering regulatory networks underlying the response of many different cellular systems to perturbations. Such a network analysis strategy using pathway information and data from multiple measurement platforms, tissues and species is a promising approach to elucidate the mechanistic underpinnings of complex diseases. Here, we present our views on the contributions that a systems approach can bring to the study of atherosclerosis, propose ways to tackle the complexity of the disease in a systems manner and review recent systems-level studies of the disease. PMID:20201031

  16. Lipidomics: A Tool for Studies of Atherosclerosis

    PubMed Central

    Ekroos, Kim; Jänis, Minna; Tarasov, Kirill; Hurme, Reini

    2010-01-01

    Lipids, abundant constituents of both the vascular plaque and lipoproteins, play a pivotal role in atherosclerosis. Mass spectrometry-based analysis of lipids, called lipidomics, presents a number of opportunities not only for understanding the cellular processes in health and disease but also in enabling personalized medicine. Lipidomics in its most advanced form is able to quantify hundreds of different molecular lipid species with various structural and functional roles. Unraveling this complexity will improve our understanding of diseases such as atherosclerosis at a level of detail not attainable with classical analytical methods. Improved patient selection, biomarkers for gauging treatment efficacy and safety, and translational models will be facilitated by the lipidomic deliverables. Importantly, lipid-based biomarkers and targets should lead the way as we progress toward more specialized therapeutics. PMID:20425241

  17. Endothelial MicroRNAs and Atherosclerosis

    PubMed Central

    Sun, Xinghui; Belkin, Nathan; Feinberg, Mark W.

    2013-01-01

    The vascular endothelium, a thin layer of endothelial cells (ECs) that line the inner surface of blood vessels, is a critical interface between blood and all tissues. EC activation, dysfunction, and vascular inflammation occur when the endothelium is exposed to various insults such as proinflammatory cytokines, oxidative stress, hypertension, hyperglycemia, aging, and shear stress. These insults lead to the pathogenesis of a range of disease states, including atherosclerosis. Several signaling pathways, especially nuclear factor ?B mediated signaling, play crucial roles in these pathophysiological processes. Recently, microRNAs (miRNAs) have emerged as important regulators of EC function by fine-tuning gene expression. In this review, we discuss how miRNAs regulate EC function and vascular inflammation in response to a variety of pathophysiologic stimuli. An understanding of the role of miRNAs in EC activation and dysfunction may provide novel targets and therapeutic opportunities for controlling atherosclerosis and other chronic inflammatory disease states. PMID:24158362

  18. Flow-dependent cellular mechanotransduction in atherosclerosis

    PubMed Central

    Conway, Daniel E.; Schwartz, Martin A.

    2013-01-01

    Summary Atherosclerosis depends on risk factors such as hyperlipidemia, smoking, hypertension and diabetes. Although these risk factors are relatively constant throughout the arterial circulation, atherosclerotic plaques occur at specific sites where flow patterns are disturbed, with lower overall magnitude and complex changes in speed and direction. Research over the past few decades has provided new insights into the cellular mechanisms of force transduction and how mechanical effects act in concert with conventional risk factors to mediate plaque formation and progression. This Commentary summarizes our current understanding of how mechanotransduction pathways synergize with conventional risk factors in atherosclerosis. We attempt to integrate cellular studies with animal and clinical data, and highlight major questions that need to be answered to develop more effective therapies. PMID:24190880

  19. Translational Coronary Atherosclerosis Imaging with PET.

    PubMed

    Adamson, Philip D; Newby, David E; Dweck, Marc R

    2016-02-01

    Although still in its infancy, coronary atherosclerosis imaging with PET holds promise in improving understanding of the pathophysiologic processes that underlie plaque progression and adverse cardiovascular events. Fludeoxyglucose F 18 offers the potential to measure inflammatory activity within the plaque itself whereas fluoride F 18 allows detection of microcalcification, both of which are key characteristics of plaques at risk of rupture. Further work is required to improve these imaging techniques and to assess their ability to predict cardiac events prospectively. PMID:26590788

  20. Computer assessment of atherosclerosis from angiographic images

    NASA Technical Reports Server (NTRS)

    Selzer, R. H.; Blankenhorn, D. H.; Brooks, S. H.; Crawford, D. W.; Cashin, W. L.

    1982-01-01

    A computer method for detection and quantification of atherosclerosis from angiograms has been developed and used to measure lesion change in human clinical trials. The technique involves tracking the vessel edges and measuring individual lesions as well as the overall irregularity of the arterial image. Application of the technique to conventional arterial-injection femoral and coronary angiograms is outlined and an experimental study to extend the technique to analysis of intravenous angiograms of the carotid and cornary arteries is described.

  1. Mesenchymal Stem Cells Reduce Murine Atherosclerosis Development.

    PubMed

    Frodermann, Vanessa; van Duijn, Janine; van Pel, Melissa; van Santbrink, Peter J; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C A

    2015-01-01

    Mesenchymal stem cells (MSCs) have regenerative properties, but recently they were also found to have immunomodulatory capacities. We therefore investigated whether MSCs could reduce atherosclerosis, which is determined by dyslipidaemia and chronic inflammation. We adoptively transferred MSCs into low-density lipoprotein-receptor knockout mice and put these on a Western-type diet to induce atherosclerosis. Initially after treatment, we found higher levels of circulating regulatory T cells. In the long-term, overall numbers of effector T cells were reduced by MSC treatment. Moreover, MSC-treated mice displayed a significant 33% reduction in circulating monocytes and a 77% reduction of serum CCL2 levels. Most strikingly, we found a previously unappreciated effect on lipid metabolism. Serum cholesterol was reduced by 33%, due to reduced very low-density lipoprotein levels, likely a result of reduced de novo hepatic lipogenesis as determined by a reduced expression of Stearoyl-CoA desaturase-1 and lipoprotein lipase. MSCs significantly affected lesion development, which was reduced by 33% in the aortic root. These lesions contained 56% less macrophages and showed a 61% reduction in T cell numbers. We show here for the first time that MSC treatment affects not only inflammatory responses but also significantly reduces dyslipidaemia in mice. This makes MSCs a potent candidate for atherosclerosis therapies. PMID:26490642

  2. Mesenchymal Stem Cells Reduce Murine Atherosclerosis Development

    PubMed Central

    Frodermann, Vanessa; van Duijn, Janine; van Pel, Melissa; van Santbrink, Peter J.; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C. A.

    2015-01-01

    Mesenchymal stem cells (MSCs) have regenerative properties, but recently they were also found to have immunomodulatory capacities. We therefore investigated whether MSCs could reduce atherosclerosis, which is determined by dyslipidaemia and chronic inflammation. We adoptively transferred MSCs into low-density lipoprotein-receptor knockout mice and put these on a Western-type diet to induce atherosclerosis. Initially after treatment, we found higher levels of circulating regulatory T cells. In the long-term, overall numbers of effector T cells were reduced by MSC treatment. Moreover, MSC-treated mice displayed a significant 33% reduction in circulating monocytes and a 77% reduction of serum CCL2 levels. Most strikingly, we found a previously unappreciated effect on lipid metabolism. Serum cholesterol was reduced by 33%, due to reduced very low-density lipoprotein levels, likely a result of reduced de novo hepatic lipogenesis as determined by a reduced expression of Stearoyl-CoA desaturase-1 and lipoprotein lipase. MSCs significantly affected lesion development, which was reduced by 33% in the aortic root. These lesions contained 56% less macrophages and showed a 61% reduction in T cell numbers. We show here for the first time that MSC treatment affects not only inflammatory responses but also significantly reduces dyslipidaemia in mice. This makes MSCs a potent candidate for atherosclerosis therapies. PMID:26490642

  3. Comparative studies of atherosclerosis in swine.

    PubMed

    Bijlenga, G; Dahme, E; Detweiler, D K; Gresham, G A; Grünberg, W; Howard, A N; Kagan, A R; Kaplan, M M; Van Nie, C J; Rubarth, S; Sternby, N H; Stünzi, H; Uemura, K; Whitney, J C

    1967-01-01

    A survey of spontaneously occurring fatty streaks and fibrous plaques, considered as atherosclerosis, in 1637 swine in different European countries and the USA, using a standardized procedure, was undertaken to determine whether significant differences exist in the occurrence and extent of the disease in various groups of animals. At the same time a preliminary study on the possible relation of any differences observed in atherosclerosis to certain environmental and constitutional factors was carried out with the ultimate goal of contributing to the understanding of analogous problems in man.STATISTICALLY SIGNIFICANT INCREASES OF FATTY STREAKS AND FIBROUS PLAQUES WERE NOTED IN RELATION TO: (a) increasing age, starting at 6 to 7 months, the earliest age period studied; (b) geographical locality; and (c) considerable as compared with moderate or slight physical activity at 1 year of age. Although not statistically significant, there was also a suggestive trend towards more atherosclerosis in pigs consuming soft water as compared with those consuming hard water.While these correlations may represent contributory factors to the increases of the changes noted in the abdominal aortas, it is not possible to pinpoint the importance of individual components because of the limited data and the large number of variables involved in this preliminary study. Studies in swine and other animals are being encouraged in which all variables but one are being kept constant to determine their possible role in the development of atherosclerotic lesions. PMID:5299676

  4. Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice[S

    PubMed Central

    Babaev, Vladimir R.; Hebron, Katie E.; Wiese, Carrie B.; Toth, Cynthia L.; Ding, Lei; Zhang, Youmin; May, James M.; Fazio, Sergio; Vickers, Kasey C.; Linton, MacRae F.

    2014-01-01

    Macrophages play crucial roles in the formation of atherosclerotic lesions. Akt, a serine/threonine protein kinase B, is vital for cell proliferation, migration, and survival. Macrophages express three Akt isoforms, Akt1, Akt2, and Akt3, but the roles of Akt1 and Akt2 in atherosclerosis in vivo remain unclear. To dissect the impact of macrophage Akt1 and Akt2 on early atherosclerosis, we generated mice with hematopoietic deficiency of Akt1 or Akt2. After 8 weeks on Western diet, Ldlr?/? mice reconstituted with Akt1?/? fetal liver cells (Akt1?/??Ldlr?/?) had similar atherosclerotic lesion areas compared with control mice transplanted with WT cells (WT?Ldlr?/?). In contrast, Akt2?/??Ldlr?/? mice had dramatically reduced atherosclerotic lesions compared with WT?Ldlr?/? mice of both genders. Similarly, in the setting of advanced atherosclerotic lesions, Akt2?/??Ldlr?/? mice had smaller aortic lesions compared with WT?Ldlr?/? and Akt1?/??Ldlr?/? mice. Importantly, Akt2?/??Ldlr?/? mice had reduced numbers of proinflammatory blood monocytes expressing Ly-6Chi and chemokine C-C motif receptor 2. Peritoneal macrophages isolated from Akt2?/? mice were skewed toward an M2 phenotype and showed decreased expression of proinflammatory genes and reduced cell migration. Our data demonstrate that loss of Akt2 suppresses the ability of macrophages to undergo M1 polarization reducing both early and advanced atherosclerosis. PMID:25240046

  5. The Bcl6–SMRT/NCoR cistrome represses inflammation to attenuate atherosclerosis

    PubMed Central

    Barish, Grant D.; Yu, Ruth T.; Karunasiri, Malith S.; Becerra, Diana; Kim, Jason; Tseng, Tiffany W.; Tai, Li-Jung; LeBlanc, Matthias; Diehl, Cody; Cerchietti, Leandro; Miller, Yury I.; Witztum, Joseph L.; Melnick, Ari M.; Dent, Alexander L.; Tangirala, Rajendra K.; Evans, Ronald M.

    2012-01-01

    SUMMARY Chronic inflammation is a hallmark of atherosclerosis, but its transcriptional underpinnings are poorly understood. We show that the transcriptional repressor Bcl6 is an anti-inflammatory regulator whose loss in bone marrow of Ldlr?/? mice results in severe atherosclerosis and xanthomatous tendonitis, a virtually pathognomonic complication in patients with familial hypercholesterolemia. Disruption of the interaction between Bcl6 and SMRT or NCoR with a peptide inhibitor in vitro recapitulated atherogenic gene changes in mice transplanted with Bcl6-deficient bone marrow, pointing to these cofactors as key mediators of Bcl6 inflammatory suppression. Using ChIP-seq, we reveal the SMRT and NCoR co-repressor cistromes, each consisting of over 30,000 binding sites with a nearly 50% overlap. While the complete cistromes identify a diversity of signaling pathways, the Bcl6-bound sub-cistromes for each co-repressor are highly enriched for NF-?B-driven inflammatory and tissue remodeling genes. These results reveal that Bcl6-SMRT/NCoR complexes constrain immune responses and contribute to the prevention of atherosclerosis. PMID:22465074

  6. LDL biochemical modifications: a link between atherosclerosis and aging

    PubMed Central

    Alique, Matilde; Luna, Carlos; Carracedo, Julia; Ramírez, Rafael

    2015-01-01

    Atherosclerosis is an aging disease in which increasing age is a risk factor. Modified low-density lipoprotein (LDL) is a well-known risk marker for cardiovascular disease. High-plasma LDL concentrations and modifications, such as oxidation, glycosylation, carbamylation and glycoxidation, have been shown to be proatherogenic experimentally in vitro and in vivo. Atherosclerosis results from alterations to LDL in the arterial wall by reactive oxygen species (ROS). Evidence suggests that common risk factors for atherosclerosis raise the likelihood that free ROS are produced from endothelial cells and other cells. Furthermore, oxidative stress is an important factor in the induction of endothelial senescence. Thus, endothelial damage and cellular senescence are well-established markers for atherosclerosis. This review examines LDL modifications and discusses the mechanisms of the pathology of atherosclerosis due to aging, including endothelial damage and oxidative stress, and the link between aging and atherosclerosis. PMID:26637360

  7. [Prevalence of aortal atherosclerosis in workers underwent occupational irradiation].

    PubMed

    Azizova, T V; Kuznetsova, K V; Bannikova, M V; Sumina, M V; Bagaeva, Ia P; Azizova, E V; Fot'eva, N P; Krupenina, L N

    2014-01-01

    The authors evaluated prevalence of aortal atherosclerosis in dependence on radiation and non-radiation factors in workers underwent occupational prolonged irradiation.The study included 22,377 workers of nuclear industry enterprise "Mayak", with verified diagnosis of aortal atherosclerosis. Up to 31th December 2008, a total of 1,840 aortal atherosclerosis cases were registered in the examinees group. Aortal atherosclerosis prevalence appeared to depend reliably on sex, age, smoking habit (in males), alcohol consumption (in males) and arterial hypertension. Findings are that aortal atherosclerosis prevalence was higher in males and females underwent external gamma-irradiation of total dose over 0.5 Gy, in males and females underwent internal alpha-irradiation from incorporated plutonium of total absorbed radiation dose in liver over 0.025 Gy. Thus, aortal atherosclerosis prevalence in workers underwent occupational irradiation de- pended both on radiational and non-radiational factors. PMID:25845141

  8. Function of CD147 in atherosclerosis and atherothrombosis.

    PubMed

    Wang, Cuiping; Jin, Rong; Zhu, Xiaolei; Yan, Jinchuan; Li, Guohong

    2015-02-01

    CD147, a member of the immunoglobulin super family, is a well-known potent inducer of extracellular matrix metalloproteinases. Studies show that CD147 is upregulated in inflammatory diseases. Atherosclerosis is a chronic inflammatory disease of the artery wall. Further understanding of the functions of CD147 in atherosclerosis and atherothrombosis may provide a new strategy for preventing and treating cardiovascular disease. In this review, we discuss how CD147 contributes to atherosclerosis and atherothrombosis. PMID:25604960

  9. Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis

    E-print Network

    Kim, YongTae

    Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a ...

  10. Is atherosclerosis fundamental to human aging? Lessons from ancient mummies.

    PubMed

    Clarke, Emily M; Thompson, Randall C; Allam, Adel H; Wann, L Samuel; Lombardi, Guido P; Sutherland, M Linda; Sutherland, James D; Cox, Samantha L; Soliman, Muhammad Al-Tohamy; Abd el-Maksoud, Gomaa; Badr, Ibrahem; Miyamoto, Michael I; Frohlich, Bruno; Nur el-din, Abdel-Halim; Stewart, Alexandre F R; Narula, Jagat; Zink, Albert R; Finch, Caleb E; Michalik, David E; Thomas, Gregory S

    2014-05-01

    Case reports from Johan Czermak, Marc Ruffer, and others a century or more ago demonstrated ancient Egyptians had atherosclerosis three millennia ago. The Horus study team extended their findings, demonstrating that atherosclerosis was prevalent among 76 ancient Egyptian mummies and among 61 mummies from each of the ancient cultures of Peru, the American Southwest, and the Aleutian Islands. These findings challenge the assumption that atherosclerosis is a modern disease caused by present day risk factors. An extensive autopsy of an ancient Egyptian teenage male weaver named Nakht found that he was infected with four parasites: Schistosoma haematobium, Taenia species, Trichinella spiralis, and Plasmodium falciparum. Modern day patients with chronic inflammatory disease such as rheumatoid arthritis, systemic lupus erythematosus, and human immunodeficiency virus experience premature atherosclerosis. Could the burden of chronic inflammatory disease have been a risk factor for atherosclerosis in these ancient cultures? The prevalence of atherosclerosis in four diverse ancient cultures is consistent with atherosclerosis being fundamental to aging. The impact of risk factors in modern times, and potentially in ancient times, suggests a strong gene-environmental interplay: human genes provide a vulnerability to atherosclerosis, the environment determines when and if atherosclerosis becomes manifest clinically. PMID:24582386

  11. Exendin-4 decreases liver inflammation and atherosclerosis development simultaneously by reducing macrophage infiltration

    PubMed Central

    Wang, Y; Parlevliet, E T; Geerling, J J; Tuin, S J L; Zhang, H; Bieghs, V; Jawad, A H M; Shiri-Sverdlov, R; Bot, I; Jager, S C A; Havekes, L M; Romijn, J A; Willems van Dijk, K; Rensen, P C N

    2014-01-01

    Background and Purpose The aetiology of inflammation in the liver and vessel wall, leading to non-alcoholic steatohepatitis (NASH) and atherosclerosis, respectively, shares common mechanisms including macrophage infiltration. To treat both disorders simultaneously, it is highly important to tackle the inflammatory status. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces hepatic steatosis and has been suggested to reduce atherosclerosis; however, its effects on liver inflammation are underexplored. Here, we tested the hypothesis that exendin-4 reduces inflammation in both the liver and vessel wall, and investigated the common underlying mechanism. Experimental Approach Female APOE*3-Leiden.CETP mice, a model with human-like lipoprotein metabolism, were fed a cholesterol-containing Western-type diet for 5 weeks to induce atherosclerosis and subsequently treated for 4 weeks with exendin-4. Key Results Exendin-4 modestly improved dyslipidaemia, but markedly decreased atherosclerotic lesion severity and area (?33%), accompanied by a reduction in monocyte adhesion to the vessel wall (?42%) and macrophage content in the plaque (?44%). Furthermore, exendin-4 reduced hepatic lipid content and inflammation as well as hepatic CD68+ (?18%) and F4/80+ (?25%) macrophage content. This was accompanied by less monocyte recruitment from the circulation as the Mac-1+ macrophage content was decreased (?36%). Finally, exendin-4 reduced hepatic chemokine expression in vivo and suppressed oxidized low-density lipoprotein accumulation in peritoneal macrophages in vitro, effects dependent on the GLP-1 receptor. Conclusions and Implications Exendin-4 reduces inflammation in both the liver and vessel wall by reducing macrophage recruitment and activation. These data suggest that exendin-4 could be a valuable strategy to treat NASH and atherosclerosis simultaneously. PMID:24490861

  12. Is the Use of Fullerene in Photodynamic Therapy Effective for Atherosclerosis?

    SciTech Connect

    Nitta, Norihisa Seko, Ayumi; Sonoda, Akinaga; Ohta, Shinichi; Tanaka, Toyohiko; Takahashi, Masashi; Murata, Kiyoshi; Takemura, Shizuki; Sakamoto, Tsutomu; Tabata, Yasuhiko

    2008-03-15

    The purpose of this study was to evaluate Fullerene as a therapeutic photosensitizer in the treatment of atherosclerosis. An atherosclerotic experimental rabbit model was prepared by causing intimal injury to bilateral external iliac arteries using balloon expansion. In four atherosclerotic rabbits and one normal rabbit, polyethylene glycol-modified Fullerene (Fullerene-PEG) was infused into the left external iliac artery and illuminated by light emitting diode (LED), while the right external iliac artery was only illuminated by LED. Two weeks later, the histological findings for each iliac artery were evaluated quantitatively and comparisons were made among atherosclerotic Fullerene+LED artery (n = 4), atherosclerotic light artery (n = 4), normal Fullerene+LED artery (n = 1), and normal light artery (n = 1). An additional two atherosclerotic rabbits were studied by fluorescence microscopy, after Fullerene-PEG-Cy5 complex infusion into the left external iliac artery, for evaluation of Fullerene-PEG incorporated within the atherosclerotic lesions. The degree of atherosclerosis in the atherosclerotic Fullerene+LED artery was significantly (p < 0.05) more severe than that in the atherosclerotic LED artery. No pathological change was observed in normal Fullerene+LED and LED arteries. In addition, strong accumulation of Fullerene-PEG-Cy5 complex within the plaque of the left iliac artery of the two rabbits was demonstrated, in contrast to no accumulation in the right iliac artery. We conclude that infusion of a high concentration of Fullerene-PEG followed by photo-illumination resulted not in a suppression of atherosclerosis but in a progression of atherosclerosis in experimental rabbit models. However, this intervention showed no adverse effects on the normal iliac artery.

  13. 75 FR 46945 - Proposed Collection; Comment Request; Multi-Ethnic Study of Atherosclerosis (MESA) Event...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-04

    ...Request; Multi-Ethnic Study of Atherosclerosis (MESA) Event Surveillance SUMMARY...Title: Multi-Ethnic Study of Atherosclerosis (MESA) Event Surveillance. Type...cardiovascular disease (CVD)-- that is, atherosclerosis and other forms of CVD that have...

  14. MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis

    PubMed Central

    Zhang, Yong; Qin, Wei; Zhang, Longyin; Wu, Xianxian; Du, Ning; Hu, Yingying; Li, Xiaoguang; Shen, Nannan; Xiao, Dan; Zhang, Haiying; Li, Zhange; Zhang, Yue; Yang, Huan; Gao, Feng; Du, Zhimin; Xu, Chaoqian; Yang, Baofeng

    2015-01-01

    Atherosclerosis, a chronic inflammatory disease, is the major cause of life-threatening complications such as myocardial infarction and stroke. Endothelial apoptosis plays a vital role in the initiation and progression of atherosclerotic lesions. Although a subset of microRNAs (miRs) have been identified as critical regulators of atherosclerosis, studies on their participation in endothelial apoptosis in atherosclerosis have been limited. In our study, we found that miR-26a expression was substantially reduced in the aortic intima of ApoE?/? mice fed with a high-fat diet (HFD). Treatment of human aortic endothelial cells (HAECs) with oxidized low-density lipoprotein (ox-LDL) suppressed miR-26a expression. Forced expression of miR-26a inhibited endothelial apoptosis as evidenced by MTT assay and TUNEL staining results. Further analysis identified TRPC6 as a target of miR-26a, and TRPC6 overexpression abolished the anti-apoptotic effect of miR-26a. Moreover, the cytosolic calcium and the mitochondrial apoptotic pathway were found to mediate the beneficial effects of miR-26a on endothelial apoptosis. Taken together, our study reveals a novel role of miR-26a in endothelial apoptosis and indicates a therapeutic potential of miR-26a for atherosclerosis associated with apoptotic cell death. PMID:25801675

  15. Lactobacillus acidophilus ATCC 4356 prevents atherosclerosis via inhibition of intestinal cholesterol absorption in apolipoprotein E-knockout mice.

    PubMed

    Huang, Ying; Wang, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili

    2014-12-01

    The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE(-/-)) mice. Eight-week-old ApoE(-/-) mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE(-/-) mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis. PMID:25261526

  16. MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis

    NASA Astrophysics Data System (ADS)

    Zhang, Yong; Qin, Wei; Zhang, Longyin; Wu, Xianxian; Du, Ning; Hu, Yingying; Li, Xiaoguang; Shen, Nannan; Xiao, Dan; Zhang, Haiying; Li, Zhange; Zhang, Yue; Yang, Huan; Gao, Feng; Du, Zhimin; Xu, Chaoqian; Yang, Baofeng

    2015-03-01

    Atherosclerosis, a chronic inflammatory disease, is the major cause of life-threatening complications such as myocardial infarction and stroke. Endothelial apoptosis plays a vital role in the initiation and progression of atherosclerotic lesions. Although a subset of microRNAs (miRs) have been identified as critical regulators of atherosclerosis, studies on their participation in endothelial apoptosis in atherosclerosis have been limited. In our study, we found that miR-26a expression was substantially reduced in the aortic intima of ApoE-/- mice fed with a high-fat diet (HFD). Treatment of human aortic endothelial cells (HAECs) with oxidized low-density lipoprotein (ox-LDL) suppressed miR-26a expression. Forced expression of miR-26a inhibited endothelial apoptosis as evidenced by MTT assay and TUNEL staining results. Further analysis identified TRPC6 as a target of miR-26a, and TRPC6 overexpression abolished the anti-apoptotic effect of miR-26a. Moreover, the cytosolic calcium and the mitochondrial apoptotic pathway were found to mediate the beneficial effects of miR-26a on endothelial apoptosis. Taken together, our study reveals a novel role of miR-26a in endothelial apoptosis and indicates a therapeutic potential of miR-26a for atherosclerosis associated with apoptotic cell death.

  17. Lactobacillus acidophilus ATCC 4356 Prevents Atherosclerosis via Inhibition of Intestinal Cholesterol Absorption in Apolipoprotein E-Knockout Mice

    PubMed Central

    Wang, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili

    2014-01-01

    The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE?/?) mice. Eight-week-old ApoE?/? mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE?/? mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis. PMID:25261526

  18. Chronic intermittent hypoxia exposure-induced atherosclerosis: a brief review.

    PubMed

    Song, Dongmei; Fang, Guoqiang; Greenberg, Harly; Liu, Shu Fang

    2015-12-01

    Obstructive sleep apnea (OSA) is highly prevalent in the USA and is recognized as an independent risk factor for atherosclerotic cardiovascular disease. Identification of atherosclerosis risk factor attributable to OSA may provide opportunity to develop preventive measures for cardiovascular risk reduction. Chronic intermittent hypoxia (CIH) is a prominent feature of OSA pathophysiology and may be a major mechanism linking OSA to arteriosclerosis. Animal studies demonstrated that CIH exposure facilitated high-cholesterol diet (HCD)-induced atherosclerosis, accelerated the progression of existing atherosclerosis, and induced atherosclerotic lesions in the absence of other atherosclerosis risk factors, demonstrating that CIH is an independent causal factor of atherosclerosis. Comparative studies revealed major differences between CIH-induced and the classic HCD-induced atherosclerosis. Systemically, CIH was a much weaker inducer of atherosclerosis. CIH and HCD differentially activated inflammatory pathways. Histologically, CIH-induced atherosclerotic plaques had no clear necrotic core, contained a large number of CD31+ endothelial cells, and had mainly elastin deposition, whereas HCD-induced plaques had typical necrotic cores and fibrous caps, contained few endothelial cells, and had mainly collagen deposition. Metabolically, CIH caused mild, but HCD caused more severe dyslipidemia. Mechanistically, CIH did not, but HCD did, cause macrophage foam cell formation. NF-?B p50 gene deletion augmented CIH-induced, but not HCD-induced atherosclerosis. These differences reflect the intrinsic differences between the two types of atherosclerosis in terms of pathological nature and underlying mechanisms and support the notion that CIH-induced atherosclerosis is a new paradigm that differs from the classic HCD-induced atherosclerosis. PMID:26407987

  19. Atherosclerosis: a chronic inflammatory disease mediated by mast cells

    PubMed Central

    Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells. PMID:26648785

  20. Modulation of atherosclerosis by N-3 polyunsaturated fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have reviewed literature regarding the effects of n-3 polyunsaturated fatty acids (PUFA) on risk factors for atherosclerosis in human subjects. Dietary intervention with long chain n-3 PUFA decreased some risk factor (s) for atherosclerosis in most human studies reviewed. These benefits resulted ...

  1. On to the road to degradation: atherosclerosis and the proteasome

    PubMed Central

    Herrmann, Joerg; Lerman, Lilach O.; Lerman, Amir

    2010-01-01

    Protein metabolism is a central element of every living cell. The ubiquitin-proteasome system (UPS) is an integral part of the protein metabolism machinery mediating post-transcriptional processing and degradation of the majority of intracellular proteins. Over the past few years, remarkable progress has been made in our understanding of the role of the UPS in vascular biology and pathobiology, particularly atherosclerosis. This review reflects on the recent developments from the effects on endothelial cells and the initial stage of atherosclerosis to the effects on vascular smooth muscle and the progression stage of atherosclerosis and finally to the effects on cell viability and the complication stage of atherosclerosis. It will conclude with the integration of the available information in a synoptic view of the involvement of the UPS in atherosclerosis. PMID:19815565

  2. Accelerated atherosclerosis in SLE: mechanisms and prevention approaches.

    PubMed

    Wilhelm, Ashley J; Major, Amy S

    2012-10-01

    Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by increased serum autoantibody levels and tissue damage. With improved diagnosis and more effective treatment of the resultant kidney disease, accelerated atherosclerosis has become a major cause of morbidity in patients suffering from SLE. Although the exact mechanisms for SLE-accelerated atherosclerosis are unknown, multiple factors have been established as potential players in this process. Among these potential players are dysregulation of T and B cell populations and increased circulating levels of inflammatory cytokines. In addition, SLE patients exhibit a proatherogenic lipid profile characterized by low HDL and high LDL and triglycerides. Recent therapeutic approaches have focused on targeting B cells, the producers of autoantibodies, but most studies do not consider the effects of these treatments on atherosclerosis. Evidence suggests that T cells play a major role in SLE-accelerated atherosclerosis. Therefore, therapies targeted at T cells may also prove invaluable in treating SLE and atherosclerosis. PMID:24672580

  3. Deficiency of the NR4A orphan nuclear receptor NOR1 in hematopoietic stem cells accelerates atherosclerosis.

    PubMed

    Qing, Hua; Liu, Yi; Zhao, Yue; Aono, Jun; Jones, Karrie L; Heywood, Elizabeth B; Howatt, Deborah; Binkley, Cassi M; Daugherty, Alan; Liang, Ying; Bruemmer, Dennis

    2014-09-01

    The NR4A orphan nuclear receptor NOR1 functions as a constitutively active transcription factor regulating cellular inflammation and proliferation. In this study, we used bone marrow transplantation to determine the selective contribution of NOR1 expression in hematopoietic stem cells to the development of atherosclerosis. Reconstitution of lethally irradiated apoE(-/-) mice with NOR1-deficient hematopoietic stem cells accelerated atherosclerosis formation and macrophage recruitment following feeding a diet enriched in saturated fat. NOR1 deficiency in hematopoietic stem cells induced splenomegaly and monocytosis, specifically the abundance of inflammatory Ly6C(+) monocytes. Bone marrow transplantation studies further confirmed that NOR1 suppresses the proliferation of macrophage and dendritic progenitor (MDP) cells. Expression analysis identified RUNX1, a critical regulator of hematopoietic stem cell expansion, as a target gene suppressed by NOR1 in MDP cells. Finally, in addition to inducing Ly6C(+) monocytosis, NOR1 deletion increased the replicative rate of lesional macrophages and induced local foam cell formation within the atherosclerotic plaque. Collectively, our studies demonstrate that NOR1 deletion in hematopoietic stem cells accelerates atherosclerosis formation by promoting myelopoiesis in the stem cell compartment and by inducing local proatherogenic activities in the macrophage, including lesional macrophage proliferation and foam cell formation. PMID:24806827

  4. Cardiac CT: atherosclerosis to acute coronary syndrome

    PubMed Central

    Munnur, Ravi Kiran; Cameron, James D.; Ko, Brian S.; Meredith, Ian T.

    2014-01-01

    Coronary computed tomographic angiography (CCTA) is a robust non-invasive method to assess coronary artery disease (CAD). Qualitative and quantitative assessment of atherosclerotic coronary stenosis with CCTA has been favourably compared with invasive coronary angiography (ICA) and intravascular ultrasound (IVUS). Importantly, it allows the study of preclinical stages of atherosclerotic disease, may help improve risk stratification and monitor the progressive course of the disease. The diagnostic accuracy of CCTA in the assessment of coronary artery bypass grafts (CABG) is excellent and the constantly improving technology is making the evaluation of stents feasible. Novel techniques are being developed to assess the functional significance of coronary stenosis. The excellent negative predictive value of CCTA in ruling out disease enables early and safe discharge of patients with suspected acute coronary syndromes (ACS) in the Emergency Department (ED). In addition, CCTA is useful in predicting clinical outcomes based on the extent of coronary atherosclerosis and also based on individual plaque characteristics such as low attenuation plaque (LAP), positive remodelling and spotty calcification. In this article, we review the role of CCTA in the detection of coronary atherosclerosis in native vessels, stented vessels, calcified arteries and grafts; the assessment of plaque progression, evaluation of chest pain in the ED, assessment of functional significance of stenosis and the prognostic significance of CCTA. PMID:25610801

  5. Antihypercholesterolemic and antioxidant efficacies of zerumbone on the formation, development, and establishment of atherosclerosis in cholesterol-fed rabbits

    PubMed Central

    Hemn, Hassan Othman; Noordin, Muhammad Mustapha; Rahman, Heshu Sulaiman; Hazilawati, Hamza; Zuki, Abubakr; Chartrand, Max Stanley

    2015-01-01

    Owing to the high incidence of cholesterol-induced cardiovascular disease, particularly atherosclerosis, the current study was designed to investigate the preventive and therapeutic efficacies of dietary zerumbone (ZER) supplementation on the formation and development of atherosclerosis in rabbits fed with a high cholesterol diet. A total of 72 New Zealand white rabbits were divided randomly on two experimental studies carried out 8 weeks apart. The first experiment was designed to investigate the prophylactic efficacy of ZER in preventing early developed atheromatous lesion. The second experimental trial was aimed at investigating the therapeutic effect of ZER in reducing the atherosclerotic lesion progression and establishment. Sudanophilia, histopathological, and ultrastructural changes showed pronounced reduction in the plaque size in ZER-medicated aortas. On the other hand, dietary supplementation of ZER for almost 10 weeks as a prophylactic measure indicated substantially decreasing lipid profile values, and similarly, plaque size in comparison with high-cholesterol non-supplemented rabbits. Furthermore, the results of oxidative stress and antioxidant biomarker evaluation indicated that ZER is a potent antioxidant in suppressing the generation of free radicals in terms of atherosclerosis prevention and treatment. ZER significantly reduced the value of malondialdehyde and augmented the value of superoxide dismutase. In conclusion, our data indicated that dietary supplementation of ZER at doses of 8, 16, and 20 mg/kg alone as a prophylactic measure, and as a supplementary treatment with simvastatin, significantly reduced early plague formation, development, and establishment via significant reduction in serum lipid profile, together with suppression of oxidative damage, and therefore alleviated atherosclerosis lesions. PMID:26347047

  6. Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis

    PubMed Central

    Dorighello, Gabriel G.; Paim, Bruno A.; Kiihl, Samara F.; Ferreira, Mônica S.; Catharino, Rodrigo R.; Vercesi, Anibal E.; Oliveira, Helena C. F.

    2016-01-01

    Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS) generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous atherosclerosis in these mice could be modulated by treatments that replenish or spare mitochondrial NADPH, named citrate supplementation, cholesterol synthesis inhibition, or both treatments simultaneously. Robust statistical analyses in pooled group data were performed in order to explain the variation of atherosclerosis lesion areas as related to the classic atherosclerosis risk factors such as plasma lipids, obesity, and oxidative stress, including liver mtROS. Using three distinct statistical tools (univariate correlation, adjusted correlation, and multiple regression) with increasing levels of stringency, we identified a novel significant association and a model that reliably predicts the extent of atherosclerosis due to variations in mtROS. Thus, results show that atherosclerosis lesion area is positively and independently correlated with liver mtROS production rates. Based on these findings, we propose that modulation of mitochondrial redox state influences the atherosclerosis extent. PMID:26635912

  7. Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis.

    PubMed

    Dorighello, Gabriel G; Paim, Bruno A; Kiihl, Samara F; Ferreira, Mônica S; Catharino, Rodrigo R; Vercesi, Anibal E; Oliveira, Helena C F

    2016-01-01

    Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS) generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous atherosclerosis in these mice could be modulated by treatments that replenish or spare mitochondrial NADPH, named citrate supplementation, cholesterol synthesis inhibition, or both treatments simultaneously. Robust statistical analyses in pooled group data were performed in order to explain the variation of atherosclerosis lesion areas as related to the classic atherosclerosis risk factors such as plasma lipids, obesity, and oxidative stress, including liver mtROS. Using three distinct statistical tools (univariate correlation, adjusted correlation, and multiple regression) with increasing levels of stringency, we identified a novel significant association and a model that reliably predicts the extent of atherosclerosis due to variations in mtROS. Thus, results show that atherosclerosis lesion area is positively and independently correlated with liver mtROS production rates. Based on these findings, we propose that modulation of mitochondrial redox state influences the atherosclerosis extent. PMID:26635912

  8. Atherosclerosis 209 (2010) 136141 Contents lists available at ScienceDirect

    E-print Network

    Kakadiaris, Ioannis

    2010-01-01

    Atherosclerosis 209 (2010) 136­141 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Computer-aided non-contrast CT coronary arteries, may con- tribute to the development of coronary atherosclerosis through local production

  9. Atherosclerosis 214 (2011) 5864 Contents lists available at ScienceDirect

    E-print Network

    Gelb, Michael

    2011-01-01

    Atherosclerosis 214 (2011) 58­64 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Group X secretory phospholipase A2 augments angiotensin 9 August 2010 Available online 19 August 2010 Keywords: Aneurysm Atherosclerosis Inflammation

  10. Atherosclerosis 210 (2010) 177182 Contents lists available at ScienceDirect

    E-print Network

    Terasaki, Mark

    2010-01-01

    Atherosclerosis 210 (2010) 177­182 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis A synonymous variant in scavenger receptor Atherosclerosis Synonymous SNPs a b s t r a c t Objective: A synonymous variant within scavenger receptor class B

  11. Atherosclerosis staging: imaging using FLIM technique

    NASA Astrophysics Data System (ADS)

    Sicchieri, Leticia B.; Barioni, Marina Berardi; Silva, Mônica Nascimento; Monteiro, Andrea Moreira; Figueiredo Neto, Antonio Martins; Ito, Amando S.; Courrol, Lilia C.

    2014-03-01

    In this work it was used fluorescence lifetime imaging (FLIM) to analyze biochemical composition of atherosclerotic plaque. For this purpose an animal experimentation was done with New Zealand rabbits divided into two groups: a control group of 4 rabbits that received a regular diet for 0, 20, 40 and 60 days; and an experimental group of 9 rabbits, divided in 3 subgroups, that were fed with 1% cholesterol diet for 20, 40 and 60 days respectively. The aortas slices stained with europium chlortetracycline were analyzed by FLIM exciting samples at 440 nm. The results shown an increase in the lifetime imaging of rabbits fed with cholesterol. It was observed that is possible to detect the metabolic changes associated with atherosclerosis at an early stage using FLIM technique exciting the tissue around 440 nm and observing autofluorescence lifetime. Lifetimes longer than 1.75 ns suggest the presence of porphyrins in the tissue and consequently, inflammation and the presence of macrophages.

  12. Atherosclerosis risk factors in pigeon squabs

    SciTech Connect

    Klumpp, S.A.; Clarkson, T.B.

    1986-03-01

    The basis for atherosclerosis susceptibility of White Carneau (WC) and resistance of Show Racer (SR) pigeons is not known. Body weight (BW), total serum cholesterol (TSC), growth of the aorta and replication of endothelial cells of the distal thoracic aorta (lesion prone site) of 1, 2 and 4 week old squabs were studied. Aortic measurements were determined morphometrically, and endothelial cell replication was quantitated by 24-hour /sup 3/H-thymidine labeling and whole-mount SEM autoradiography. From hatching to 4 weeks, BW increased more in WC than SR (22 to 473 gm in WC vs 19 to 416 gm in SR, p < 0.05) in WC than SR (197, 243 and 338 mg/dl in WC and 125, 194 and 282 mg/dl in SR). Surface area of the aorta between 1 and 4 weeks increased by 63% (109, 154 and 178 mm/sup 2/) in WC and 44% (101, 140 and 146 mm/sup 2/) in SR. Aortic surface area was significantly larger (0 = 0.002) in the 4 week WC than 4 week SR. /sup 3/H-thymidine labeled endothelial cells at 1, 2 and 4 weeks were 783, 387 and 53 in WC and 674, 283 and 27 cells/mm/sup 2/ in SR. Endothelial replication in the 4 week WC was twice that of the SR and significantly different between breeds at 2 and 4 weeks (p = 0.04; p = 0.02, respectively). Higher TSC, endothelial cell replication and larger aortic surface area in the WC may be contributing factors to increased atherosclerosis susceptibility.

  13. Systemic lupus erythematosus and atherosclerosis: Review of the literature.

    PubMed

    Frieri, Marianne; Stampfl, Heather

    2016-01-01

    The purpose of this manuscript is to extensively review the literature related to systemic lupus erythematosus and atherosclerosis. The conclusion of this review has covered accelerated atherosclerosis in systemic lupus erythematosus, the role of complement, interferon in premature atherosclerosis, inflammatory mediators such as cytokines, leukocytes, innate and adaptive immunity, hydrolytic enzymes, reactive oxygen species, vascular endothelial growth factor, toll receptors in lupus nephritis, several specific anti-inflammatory pharmacological therapies, and potential prevention strategies for atherothrombotic events, interferons and the inflammasome. It is important for allergist-immunologists, rheumatologists both in academic institutions and in practice to understand this important disorder. PMID:26299985

  14. Roles of antibody against oxygenized low density lipoprotein in atherosclerosis: recent advances

    PubMed Central

    Zhang, Jing; Wang, Daxin; He, Shenghu

    2015-01-01

    Atherosclerosis is a chronic immune inflammatory disease. Atherosclerosis and relevant disease are threatening human life and health. Oxygenized low density lipoprotein (oxLDL) is a molecular basis in the pathogenesis of atherosclerosis and able to induce inflammation, stimulate immune system and interfere with lipid metabolism in the occurrence and development of atherosclerosis. Antibody against oxLDL has been an important molecule in the immune related pathogenesis of atherosclerosis. In available studies on atherosclerosis, antibody against oxLDL has been a focus, but how oxLDL acts to affect the atherosclerosis and relevant diseases, whether oxLDL is protective or detrimental, and whether oxLDL acts in different ways at different stages of atherosclerosis are still unclear. This paper focuses on the role of antibody against oxLDL in the atherosclerosis and relevant diseases, and summarizes the advances in this field, aiming to provide new clue and new methods for the therapy of atherosclerosis. PMID:26550105

  15. Association of blood lactate with carotid atherosclerosis: The Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study

    PubMed Central

    Subash Shantha, Ghanshyam Palamaner; Wasserman, Bruce; Astor, Brad C.; Coresh, Josef; Brancati, Fredrick; Sharrett, A. Richey; Young, J. Hunter

    2013-01-01

    Objectives Cardiovascular risk factors such as aging, smoking, and insulin resistance may lead to atherosclerosis through various mechanisms of which their association with mitochondrial dysfunction may be one of them. In order to examine this hypothesis, we assessed the association between elevated blood lactate, a marker of mitochondrial dysfunction, and carotid atherosclerosis. Methods From a total of 2066 participants from the Atherosclerosis Risk In Communities Carotid MRI study, 1496 were included for this analysis. Wall Thickness and Lipid core presence were measured using gadolinium-enhanced MRI. Blood lactate was categorized into quartiles (Q1: < 5.9 mg/dl, Q2: 5.9 to 7.2mg/dl, Q3: 7.3 to 9.2 mg/dl, and Q4: >9.2 mg/dl). Results Of the 1496 study participants, 763 (51%) were females, 296 (19.8%) African American, 539 (36%) obese and 308 (20.6%) had diabetes. There was a strong and graded association between lactate and wall thickness [Q1: 1.08 mm (95% CI: 1.01 mm – 1.15 mm), Q2: 1.33 mm (95% CI: 1.19 mm – 1.47 mm), Q3: 1.44 (95% CI: 1.34 mm – 1.54 mm) and Q4: 1.62 (95% CI: 1.53 mm – 1.71 mm); p for trend <0.001] after adjusting for age, gender, ethnicity, stature, body mass index (BMI), waist circumference, LDL, High sensitivity C reactive protein (HsCRP), statin use, thiazolodinedione use, hypertension, and diabetes. This association was attenuated, but still significant, after adjusting for a marker of insulin resistance, the triglyceride/HDL ratio, [Q1: 0.96 mm (95% CI: 0.82 mm – 1.10 mm), Q2: 1.17 mm (95% CI: 1.08 mm – 1.26 mm), Q3: 1.18 mm (95% CI: 1.07 mm – 1.29 mm), Q4: 1.22 mm (95% CI: 1.13 mm – 1.31 mm), p for linear trend 0.039]. There was no association of lactate with lipid core presence after adjustment for wall thickness. Conclusions Blood lactate is associated with carotid atherosclerosis. Attenuation of the association with adjustment for triglyceride/HDL ratio, a marker of insulin resistance, suggests that lactate’s association with carotid atherosclerosis may be related to insulin resistance. PMID:23510829

  16. Short and Long-Term Effects of the Angiotensin II Receptor Blocker Irbesartan on Intradialytic Central Hemodynamics: A Randomized Double-Blind Placebo-Controlled One-Year Intervention Trial (the SAFIR Study)

    PubMed Central

    Peters, Christian Daugaard; Kjaergaard, Krista Dybtved; Jensen, Jens Dam; Christensen, Kent Lodberg; Strandhave, Charlotte; Tietze, Ida Noerager; Novosel, Marija Kristina; Bibby, Bo Martin; Jespersen, Bente

    2015-01-01

    Background and Aim Little is known about the tolerability of antihypertensive drugs during hemodialysis treatment. The present study evaluated the use of the angiotensin II receptor blocker (ARB) irbesartan. Design Randomized, double-blind, placebo-controlled, one-year intervention trial. Setting and Participants Eighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage <1 year. Intervention Irbesartan/placebo 300 mg/day for 12 months administered as add-on to antihypertensive treatment using a predialytic systolic blood pressure target of 140 mmHg in all patients. Outcomes and Measurements Cardiac output, stroke volume, central blood volume, total peripheral resistance, mean arterial blood pressure, and frequency of intradialytic hypotension. Results At baseline, the groups were similar regarding age, comorbidity, blood pressure, antihypertensive medication, ultrafiltration volume, and dialysis parameters. Over the one-year period, predialytic systolic blood pressure decreased significantly, but similarly in both groups. Mean start and mean end cardiac output, stroke volume, total peripheral resistance, heart rate, and mean arterial pressure were stable and similar in the two groups, whereas central blood volume increased slightly but similarly over time. The mean hemodynamic response observed during a dialysis session was a drop in cardiac output, in stroke volume, in mean arterial pressure, and in central blood volume, whereas heart rate increased. Total peripheral resistance did not change significantly. Overall, this pattern remained stable over time in both groups and was uninfluenced by ARB treatment. The total number of intradialytic hypotensive episodes was (placebo/ARB) 50/63 (P = 0.4). Ultrafiltration volume, left ventricular mass index, plasma albumin, and change in intradialytic total peripheral resistance were significantly associated with intradialytic hypotension in a multivariate logistic regression analysis based on baseline parameters. Conclusion Use of the ARB irbesartan as an add-on to other antihypertensive therapy did not significantly affect intradialytic hemodynamics, neither in short nor long-term, and no significant increase in hypotensive episodes was seen. Trial registration Clinicaltrials.gov NCT00791830 PMID:26030651

  17. Calcific aortic valve disease: Is it another face of atherosclerosis?

    PubMed

    Sathyamurthy, I; Alex, Shaji

    2015-01-01

    Calcific aortic valve disease (CAVD) is the most common valvular heart disease in the elderly. As life expectancy increases, prevalence of CAVD is expected to rise. CAVD is characterized by progressive dystrophic calcification of aortic cusps. In the initial stages, the pathogenesis is similar to atherosclerosis, characterized by basement membrane disruption, inflammation, cell infiltration, lipid deposition, and calcification. Presence of osteopontin in calcified aortic valves suggests pathological calcification and bone formation in these calcified valves. Historical, experimental, genetic, and clinical evidences suggest that CAVD and atherosclerosis share the same pathological sequences with common risk factors. Understanding the two faces of atherosclerosis, the vascular and valvular, will help us to prevent progression of aortic sclerosis to aortic stenosis, by controlling modifiable risk factors and by initiating statin therapy in them. However, the knowledge about these preventive measures and drugs is scanty. In this review article, an attempt is made to unfurl the relation between atherosclerosis and CAVD. PMID:26432749

  18. Design of a bead holder for thermal atherosclerosis sensor

    E-print Network

    Savage, Christopher (Christopher R.)

    2007-01-01

    Atherosclerosis is a systemic disease that causes plaque accumulation in arteries and diminished endothelial function. Because it is rarely identified until serious symptoms appear, there is value in a noninvasive technique ...

  19. IL-17-dependent Autoimmunity to Collagen Type V in Atherosclerosis

    PubMed Central

    Dart, Melanie L.; Jankowska-Gan, Ewa; Huang, Guorui; Roenneburg, Drew A.; Keller, Melissa R.; Torrealba, Jose R.; Rhoads, Aaron; Kim, Byoungjae; Bobadilla, Joseph L.; Haynes, Lynn D.; Wilkes, David S.; Burlingham, William J.; Greenspan, Daniel S.

    2010-01-01

    Rationale Considerable evidence shows atherosclerosis to be a chronic inflammatory disease in which immunity to self-antigens contributes to disease progression. We recently identified the collagen V [col(V)] ?1(V) chain as a key autoantigen driving the Th17-dependent cellular immunity underlying another chronic inflammatory disease, obliterative bronchiolitis. Since specific induction of ?1(V) chains has previously been reported in human atheromas, we postulated involvement of col(V) autoimmunity in atherosclerosis. Objective To determine whether col(V) autoimmunity may be involved in the pathogenesis of atherosclerosis. Methods and Results Here we demonstrate Th17-dependent anti-col(V) immunity to be characteristic of atherosclerosis in human coronary artery disease (CAD) patients and in apolipoprotein E null (ApoE?/?) atherosclerotic mice. Responses were ?1(V)-specific in CAD with variable Th1 pathway involvement. In early atherosclerosis in ApoE?/? mice, anti-col(V) immunity was tempered by an IL-10-dependent mechanism. In support of a causal role for col(V) autoimmunity in the pathogenesis of atherosclerosis, col(V)-sensitization of ApoE?/? mice on a regular chow diet overcame IL-10-mediated inhibition of col(V) autoimmunity, leading to increased atherosclerotic burden in these mice and local accumulation of IL-17 producing cells, particularly in the col(V)-rich adventitia subjacent to the atheromas. Conclusions These findings establish col(V) as an autoantigen in human CAD and show col(V) autoimmunity to be a consistent feature in atherosclerosis in humans and mice. Furthermore, data are consistent with a causative role for col(V) in the pathogenesis of atherosclerosis. PMID:20814021

  20. Subclinical atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus.

    PubMed

    Salmon, Jane E; Roman, Mary J

    2008-10-01

    Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with increased mortality, largely as a consequence of cardiovascular disease. Increased cardiovascular morbidity and mortality in patients with RA and SLE cannot be entirely explained by traditional risk factors, suggesting that the systemic inflammation that characterizes these diseases may accelerate atherosclerosis. We used carotid ultrasonography to investigate the prevalence and correlates to preclinical atherosclerosis in patients with RA and SLE. Because atherosclerosis is a systemic disease, assessment of carotid plaque by ultrasonography provides a robust, direct measure of systemic atherosclerosis. We observed a substantially increased prevalence of carotid plaque in RA and SLE patients compared with age- and sex-matched controls, which remained after adjustment for traditional risk factors. The presence of carotid atherosclerosis was associated with disease duration in both RA and SLE and damage in SLE. These data support the hypothesis that inflammation associated with RA and SLE contributes to accelerated atherosclerosis and argue that RA and SLE disease activity should be more aggressively managed. PMID:18926167

  1. Human oral, gut, and plaque microbiota in patients with atherosclerosis

    PubMed Central

    Koren, Omry; Spor, Aymé; Felin, Jenny; Fåk, Frida; Stombaugh, Jesse; Tremaroli, Valentina; Behre, Carl Johan; Knight, Rob; Fagerberg, Björn; Ley, Ruth E.; Bäckhed, Fredrik

    2011-01-01

    Periodontal disease has been associated with atherosclerosis, suggesting that bacteria from the oral cavity may contribute to the development of atherosclerosis and cardiovascular disease. Furthermore, the gut microbiota may affect obesity, which is associated with atherosclerosis. Using qPCR, we show that bacterial DNA was present in the atherosclerotic plaque and that the amount of DNA correlated with the amount of leukocytes in the atherosclerotic plaque. To investigate the microbial composition of atherosclerotic plaques and test the hypothesis that the oral or gut microbiota may contribute to atherosclerosis in humans, we used 454 pyrosequencing of 16S rRNA genes to survey the bacterial diversity of atherosclerotic plaque, oral, and gut samples of 15 patients with atherosclerosis, and oral and gut samples of healthy controls. We identified Chryseomonas in all atherosclerotic plaque samples, and Veillonella and Streptococcus in the majority. Interestingly, the combined abundances of Veillonella and Streptococcus in atherosclerotic plaques correlated with their abundance in the oral cavity. Moreover, several additional bacterial phylotypes were common to the atherosclerotic plaque and oral or gut samples within the same individual. Interestingly, several bacterial taxa in the oral cavity and the gut correlated with plasma cholesterol levels. Taken together, our findings suggest that bacteria from the oral cavity, and perhaps even the gut, may correlate with disease markers of atherosclerosis. PMID:20937873

  2. Obstructive Sleep Apnea, Hypertension, and Their Additive Effects on Atherosclerosis

    PubMed Central

    Damiani, Mario Francesco; Zito, Annapaola; Carratù, Pierluigi; Falcone, Vito Antonio; Bega, Elioda; Scicchitano, Pietro; Ciccone, Marco Matteo; Resta, Onofrio

    2015-01-01

    Background and Aims. It is widely accepted that obstructive sleep apnea (OSA) is independently associated with atherosclerosis. Similar to OSA, hypertension (HTN) is a condition associated with atherosclerosis. However, to date, the impact of the simultaneous presence of OSA and HTN on the risk of atherosclerosis has not been extensively studied. The aim of this study was to evaluate the consequences of the coexistence of OSA and HTN on carotid intima-media thickness (IMT) and on inflammatory markers of atherosclerosis (such as interleukin- [IL-] 6 and pentraxin- [PTX-] 3). Methods. The study design allowed us to define 4 groups: (1) controls (n = 30); (2) OSA patients without HTN (n = 30); (3) HTN patients without OSA (n = 30); (4) patients with OSA and HTN (n = 30). In the morning after portable monitoring (between 7 am and 8 am), blood samples were collected, and carotid IMT was measured. Results. Carotid IMT, IL-6, and PTX-3 in OSA normotensive patients and in non-OSA HTN subjects were significantly higher compared to control subjects; in addition, in OSA hypertensive patients they were significantly increased compared to OSA normotensive, non-OSA HTN, or control subjects. Conclusions. OSA and HTN have an additive role in the progression of carotid atherosclerosis and in blood levels of inflammatory markers for atherosclerosis, such as interleukin-6 and pentraxin-3.

  3. Suppression of adrenal ?arrestin1-dependent aldosterone production by ARBs: head-to-head comparison

    PubMed Central

    Dabul, Samalia; Bathgate-Siryk, Ashley; Valero, Thairy Reyes; Jafferjee, Malika; Sturchler, Emmanuel; McDonald, Patricia; Koch, Walter J.; Lymperopoulos, Anastasios

    2015-01-01

    The known angiotensin II (AngII) physiological effect of aldosterone synthesis and secretion is mediated by either Gq/11 proteins or ?arrestin1 (?arr1), both of which can couple to its type 1 receptors (AT1Rs), present in adrenocortical zona glomerulosa (AZG) cell membranes. In the present study, we examined the relative potencies of all the currently used in the clinic AT1R antagonist drugs (angiotensin receptor blockers, ARBs, or sartans) at preventing activation of these two signaling mediators (G proteins and ?arrs) at the AngII-bound AT1R and, consequently, at suppression of aldosterone in vitro. All ARBs were found to be potent inhibitors of G protein activation at the AT1R. However, candesartan and valsartan were the most potent at blocking AngII-induced ?arr activation at this receptor, among the tetrazolo-biphenyl-methyl derivatives, translating into excellent efficacies at aldosterone suppression in H295R cells. Conversely, irbesartan and losartan were largely G protein-selective inhibitors at the AT1R, with very low potency towards ?arr inhibition. As a result, they were very weak suppressors of ?arr1-dependent aldosterone production in H295R cells. These findings provide important pharmacological insights into the drug class of ARBs and medicinal chemistry insights for future drug development in the field of AngII antagonism. PMID:25631300

  4. Purification, structure features and anti-atherosclerosis activity of a Laminaria japonica polysaccharide.

    PubMed

    Peng, Fu-Hua; Zha, Xue-Qiang; Cui, Shao-Hua; Asghar, Muhammad-Naeem; Pan, Li-Hua; Wang, Jun-Hui; Luo, Jian-Ping

    2015-11-01

    A homogeneous polysaccharide (LJP12) was isolated from Laminaria japonica by diethylaminoethyl-cellulose and Sephacryl S-500 chromatography, with a molecular weight of 2.31×10(6)Da. Monosaccharide analysis showed that LJP12 was mainly composed of arabinose, xylose, mannose, glucose and galactose in a molar ratio of 1:0.17:1.54:2.64:0.18. For these monosaccharides, mannose was suggested to be 1,4-linked and 1,3,6-linked while glucose was linked by 1,6-glycosidic bond. The xylose, arabinose and galactose were suggested to be the terminal residues. To study the effects of LJP12 on protecting against atherosclerosis, LJP12 was administered to LDL receptor-deficient (LDLr(-/-)) mice (50, 100 and 200mg/kg/day, n=30 for each experimental group). Results showed that LJP12 exhibited the ability to inhibit high-fat-cholesterol diet (HFD)-induced formation of atherosclerotic plaques and plasma lipid levels in a dose-dependent manner. Meanwhile, both the HFD-induced systemic inflammation and local inflammation at the site of atherosclerotic lesion were significantly attenuated by LJP12, which were accompanied by the suppression of the activation of nuclear factor kappa-B (NF-?B) and mitogen-activated protein kinases (MAPKs) signaling pathways. Taken together, we concluded that long-term oral administration of LJP12 protects against atherosclerosis in LDLr(-/-) mice via inhibiting NF-?B/MAPKs-mediated inflammatory responses. PMID:26394383

  5. Endothelium Preserving Microwave Treatment for Atherosclerosis

    NASA Technical Reports Server (NTRS)

    Carl, James R. (Inventor); Arndt, Dickey (Inventor); Fink, Patrick W. (Inventor); Beer, Reginald (Inventor); Henry, Phillip D. (Inventor); Pacifico, Antonio (Inventor); Raffoul, George W. (Inventor)

    2002-01-01

    Method and apparatus are provided to treat atherosclerosis wherein the artery is partially closed by dilating the artery while preserving the vital and sensitive endothelial layer thereof. Microwave energy having a frequency from 3 GHz to 300 GHz is propagated into the arterial wall to produce a desired temperature profile therein at tissue depths sufficient for thermally necrosing connective tissue and softening fatty and waxy plaque while limiting heating of surrounding tissues including the endothelial layer and/or other healthy tissue, organs, and blood. The heating period for raising the temperature a potentially desired amount, about 20 C. within the atherosclerotic lesion may be less than about one second. In one embodiment of the invention, a radically beveled waveguide antenna is used to deliver microwave energy at frequencies from 25 GHz or 30 GHz to about 300 GHz and is focused towards a particular radial sector of the artery. Because the atherosclerotic lesions are often asymmetrically disposed, directable or focussed heating preserves healthy sectors or the artery and applies energy to the asymmetrically positioned lesion faster than a non-directed bean. A computer simulation predicts isothermic temperature profiles for the given conditions and may be used in selecting power, pulse duration, beam width, and frequency of operation to maximize energy deposition and control heat rise within the atherosclerotic lesion without harming healthy tissues or the sensitive endothelium cells.

  6. Endothelium Preserving Microwave Treatment for Atherosclerosis

    NASA Technical Reports Server (NTRS)

    Carl, James R. (Inventor); Arndt, G. Dickey (Inventor); Fink, Patrick W. (Inventor); Beer, N. Reginald (Inventor); Henry, Phillip D. (Inventor); Pacifico, Antonio (Inventor); Raffoul, George W. (Inventor)

    2001-01-01

    Method and apparatus are provided to treat atherosclerosis wherein the artery is partially closed by dilating the artery while preserving the vital and sensitive endothelial layer thereof. Microwave energy having a frequency from 3 GHz to 300 GHz is propagated into the arterial wall to produce a desired temperature profile therein at tissue depths sufficient for thermally necrosing connective tissue and softening fatty and waxy plaque while limiting heating of surrounding tissues including the endothelial layer and/or other healthy tissue, organs, and blood. The heating period for raising the temperature a potentially desired amount, about 20 C. within the atherosclerotic lesion may be less than about one second. In one embodiment of the invention, a radically beveled waveguide antenna is used to deliver microwave energy at frequencies from 25 GHz or 30 GHz to about 300 GHz and is focused towards a particular radial sector of the artery. Because the atherosclerotic lesions are often asymmetrically disposed directable or focussed heating preserves healthy sectors of the artery and applies energy to the asymmetrically positioned lesion faster than a non-directed beam. A computer simulation predicts isothermic temperature profiles for the given conditions and may be used in selecting power, pulse duration, beam width, and frequency of operation to maximize energy deposition and control heat rise within the atherosclerotic lesion without harming healthy tissues or the sensitive endothelium cells.

  7. Endothelium Preserving Microwave Treatment for Atherosclerosis

    NASA Technical Reports Server (NTRS)

    Carl, James R. (Inventor); Arndt, G. Dickey (Inventor); Fink, Patrick W. (Inventor); Beer, N. Reginald (Inventor); Henry, Phillip D. (Inventor); Pacifico, Antonio (Inventor); Raffoul, George W. (Inventor)

    2000-01-01

    Method and apparatus are provided to treat atherosclerosis wherein the artery is partially closed by dilating the artery while preserving the vital and sensitive endothelial layer thereof Microwave energy having a frequency from 3 GHz to 300 GHz is propagated into the arterial wall to produce a desired temperature profile therein at tissue depths sufficient for thermally necrosing connective tissue and softening fatty and waxy plaque while limiting heating of surrounding tissues including the endothelial laser and/or other healthy tissue, organs, and blood. The heating period for raising the temperature a potentially desired amount, about 20 C., within the atherosclerotic lesion may be less than about one second. In one embodiment of the invention, a radically beveled waveguide antenna is used to deliver microwave energy at frequencies from 25 GHz or 30 GHz to about 300 GHz and is focused towards a particular radial sector of the artery. Because the atherosclerotic lesions are often asymmetrically disposed, directable of focussed heating preserves healthy sectors of the artery and applies energy to the asymmetrically positioned lesion faster than a non-directed beam. A computer simulation predicts isothermic temperature profiles for the given conditions and man be used in selecting power, pulse duration, beam width, and frequency of operation to maximize energy deposition and control heat rise within the atherosclerotic lesion without harming healthy tissues or the sensitive endothelium cells.

  8. Genomic correlates of atherosclerosis in ancient humans.

    PubMed

    Zink, Albert; Wann, L Samuel; Thompson, Randall C; Keller, Andreas; Maixner, Frank; Allam, Adel H; Finch, Caleb E; Frohlich, Bruno; Kaplan, Hillard; Lombardi, Guido P; Sutherland, M Linda; Sutherland, James D; Watson, Lucia; Cox, Samantha L; Miyamoto, Michael I; Narula, Jagat; Stewart, Alexandre F R; Thomas, Gregory S; Krause, Johannes

    2014-06-01

    Paleogenetics offers a unique opportunity to study human evolution, population dynamics, and disease evolution in situ. Although histologic and computed x-ray tomographic investigations of ancient mummies have clearly shown that atherosclerosis has been present in humans for more than 5,000 years, limited data are available on the presence of genetic predisposition for cardiovascular disease in ancient human populations. In a previous whole-genome study of the Tyrolean Iceman, a 5,300-year-old glacier mummy from the Alps, an increased risk for coronary heart disease was detected. The Iceman's genome revealed several single nucleotide polymorphisms that are linked with cardiovascular disease in genome-wide association studies. Future genetic studies of ancient humans from various geographic origins and time periods have the potential to provide more insights into the presence and possible changes of genetic risk factors in our ancestors. The study of ancient humans and a better understanding of the interaction between environmental and genetic influences on the development of heart diseases may lead to a more effective prevention and treatment of the most common cause of death in the modern world. PMID:25667090

  9. Yindanxinnaotong, a Chinese compound medicine, synergistically attenuates atherosclerosis progress

    PubMed Central

    Cheng, Long; Pan, Guo-feng; Zhang, Xiao-dong; Wang, Jian-lu; Wang, Wan-dan; Zhang, Jian-yong; Wang, Hui; Liang, Ri-xin; Sun, Xiao-bo

    2015-01-01

    Yindanxinnaotong (YD), a traditional Chinese medicine, has been introduced to clinical medicine for more than a decade, while its pharmacological properties are still not to be well addressed. This report aimed to explore the anti-atherosclerosis properties and underlying mechanisms of YD. We initially performed a computational prediction based on a network pharmacology simulation, which clued YD exerted synergistically anti-atherosclerosis properties by vascular endothelium protection, lipid-lowering, anti-inflammation, and anti-oxidation. These outcomes were then validated in atherosclerosis rats. The experiments provided evidences indicating YD’s contribution in this study included, (1) significantly reduced the severity of atherosclerosis, inhibited reconstruction of the artery wall and regulated the lipid profile; (2) enhanced antioxidant power, strengthened the activity of antioxidant enzymes, and decreased malondialdhyde levels; (3) significantly increased the viability of umbilical vein endothelial cells exposed to oxidative stress due to pretreatment with YD; (4) significantly reduced the level of pro-inflammatory cytokines; (5) significantly down-regulated NF-kB/p65 and up-regulated IkB in the YD-treated groups. Overall, these results demonstrated that YD intervention relieves atherosclerosis through regulating lipids, reducing lipid particle deposition in the endothelial layer of artery, enhancing antioxidant power, and repressing inflammation activity by inhibiting the nuclear factor-kappa B signal pathway. PMID:26196108

  10. Interleukin-4, Oxidative Stress, Vascular Inflammation and Atherosclerosis

    PubMed Central

    Lee, Yong Woo; Kim, Paul H.; Lee, Won Hee; Hirani, Anjali A.

    2010-01-01

    The pro-oxidative and pro-inflammatory pathways in vascular endothelium have been implicated in the initiation and progression of atherosclerosis. In fact, inflammatory responses in vascular endothelium are primarily regulated through oxidative stress-mediated signaling pathways leading to overexpression of pro-inflammatory mediators. Enhanced expression of cytokines, chemokines and adhesion molecules in endothelial cells and their close interactions facilitate recruiting and adhering blood leukocytes to vessel wall, and subsequently stimulate transendothelial migration, which are thought to be critical early pathologic events in atherogenesis. Although interleukin-4 (IL-4) was traditionally considered as an anti-inflammatory cytokine, recent in vitro and in vivo studies have provided robust evidence that IL-4 exerts pro-inflammatory effects on vascular endothelium and may play a critical role in the development of atherosclerosis. The cellular and molecular mechanisms responsible for IL-4-induced atherosclerosis, however, remain largely unknown. The present review focuses on the distinct sources of IL-4-mediated reactive oxygen species (ROS) generation as well as the pivotal role of ROS in IL-4-induced vascular inflammation. These studies will provide novel insights into a clear delineation of the oxidative mechanisms of IL-4-mediated stimulation of vascular inflammation and subsequent development of atherosclerosis. It will also contribute to novel therapeutic approaches for atherosclerosis specifically targeted against pro-oxidative and pro-inflammatory pathways in vascular endothelium. PMID:21072258

  11. Antigen-Induced Immunomodulation in the Pathogenesis of Atherosclerosis

    PubMed Central

    Milioti, Natalia; Bermudez-Fajardo, Alexandra; Penichet, Manuel L.; Oviedo-Orta, Ernesto

    2008-01-01

    Atherosclerosis is a chronic inflammatory disorder characterised by the accumulation of monocytes/macrophages, smooth muscle cells, and lymphocytes within the arterial wall in response to the release of proinflammatory molecules. Such accumulation results in the formation of the atherosclerotic plaque, which would eventually evolve to complications such as total artery occlusion, rupture, calcification, or aneurysm. Although the molecular mechanism responsible for the development of atherosclerosis is not completely understood, it is clear that the immune system plays a key role in the development of the atherosclerotic plaque and in its complications. There are multiple antigenic stimuli that have been associated with the pathogenesis of atherosclerosis. Most of these stimuli come from modified self-molecules such as oxidised low-density lipoproteins (oxLDLs), beta2glycoprotein1 (?2GP1), lipoprotein a (LP(a)), heat shock proteins (HSPs), and protein components of the extracellular matrix such as collagen and fibrinogen in the form of advanced glycation-end (AGE) products. In addition, several foreign antigens including bacteria such as Porphyromonas gingivalis and Chlamydia pneumoniae and viruses such as enterovirus and cytomegalovirus have been associated with atherosclerosis as potentially causative or bystander participants, adding another level of complexity to the analysis of the pathophysiology of atherosclerosis. The present review summarises the most important scientific findings published within the last two decades on the importance of antigens, antigen stimulation, and adaptive immune responses in the development of atherosclerotic plaques. PMID:18551190

  12. Beyond cholesterol: the enigma of atherosclerosis revisited.

    PubMed

    Bhakdi, Sucharit; Lackner, Karl J; Han, Shan-Rui; Torzewski, Michael; Husmann, Matthias

    2004-04-01

    Atherosclerosis is widely regarded as a chronic inflammatory disease that develops as a consequence of entrapment of low density lipoprotein (LDL) in the arterial intima. Native LDL lacks inflammatory properties, so the lipoprotein must undergo biochemical alterations in order to become atherogenic. Modification is commonly regarded as being dangerous because it bestows inflammatory properties onto the lipoprotein. Most current models consider oxidation to be the decisive modifying event. Here, we submit a different concept for discussion. We propose that modification of tissue-entrapped LDL is required because it enables the lipoprotein to signal to the immune system and effect its own removal. Oxidation would be too haphazard to fulfill this function. We summarize the evidence indicating that modification occurs through the action of ubiquitous hydrolytic enzymes. Enzymatically remodeled LDL binds C-reactive protein. C-reactive protein bound to remodeled LDL not only activates complement but also regulates it by inhibiting activation of the terminal complement cascade. Simultaneously, epitopes are exposed to enable the lipoprotein to be recognized and taken up by macrophages. The high density lipoprotein-dependent reverse transport pathway concludes the sequence of events that clear tissues of cholesterol in a non-inflammatory manner very similar to what has been described for the removal of apoptotic cells. It is proposed that these physiological processes occur throughout life without harm, pathology evolving only when the machinery suffers overload. Detrimental effects are then evoked primarily by the unreigned activation of complement, macrophages, and other effectors of the immune system in the lesions. PMID:15045123

  13. Hemodynamic sequelae of regression of experimental atherosclerosis.

    PubMed Central

    Armstrong, M L; Heistad, D D; Marcus, M L; Piegors, D J; Abboud, F M

    1983-01-01

    Regression of experimental atherosclerosis is characterized by decreased intimal thickness and luminal enlargement, but intimal fibrosis becomes more dense. We tested the hypothesis that fibrosis of arteries during regression might limit vasodilator capacity and restrict hemodynamic improvement despite luminal improvement. We studied limb, coronary, and cerebral hemodynamics in 11 normal cynomolgus monkeys, 10 monkeys given an atherogenic diet for 20 mo and 8 monkeys given a regression diet for an additional 18 mo. The atherogenic diet induced lesions of moderate severity (50-60% stenosis); owing to characteristic vessel growth during the atherogenic period, luminal size did not decrease correspondingly. Regression monkeys showed typical changes of regression with luminal enlargement but increased fibrosis. The iliac artery was perfused at constant blood flow and maximal vasodilatation was produced with papaverine. Blood flow was measured with microspheres during maximal vasodilatation in the coronary bed (adenosine) and cerebral bed (hypercapnia). In normal monkeys, minimal vascular resistances were 1.95 +/- 0.19 mm Hg/ml/min X 100 g (mean +/- SE) (limb), 0.13 +/- 0.01 (coronary), and 0.44 +/- 0.02 (cerebral). In atherosclerotic monkeys minimal resistance increased (P less than 0.05) 108, 62, and 166% in the limb, coronary, and cerebral beds, respectively. In regression monkeys, minimal resistance increased from values found in atherosclerotic animals in the limb (+22%), decreased inconsistently in the coronary bed (-19%), and decreased significantly in the cerebral bed (-44%, P less than 0.05). Thus morphologic regression was accompanied by significant hemodynamic improvement during maximal dilatation only in cerebral vessels. We conclude that increases in luminal size during regression of atherosclerotic lesions may not be associated with increases in vasodilator capacity, as intimal fibrosis may limit physiologically important hemodynamic improvement. PMID:6848553

  14. 75 FR 62544 - Proposed Collection; Comment Request; the Atherosclerosis Risk in Communities Study (ARIC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... SERVICES National Institutes of Health Proposed Collection; Comment Request; the Atherosclerosis Risk in... approval. Proposed Collection: Title: The Atherosclerosis Risk in Communities Study (ARIC). Type of...' cardiovascular events. Information gathered will be used to further describe the risk factors, occurrence...

  15. SUSCEPTIBILITY TO ATHEROSCLEROSIS IN AORTAS AND CORONARY ARTERIES OF SWINE WITH VON WILLEBRAND'S DISEASE

    EPA Science Inventory

    The development of coronary and aortic atherosclerosis was determined after balloon catheter injury of coronary arteries and administration of an atherogenic diet in normal pigs and pigs that were homozygous and heterozygous for von Willebrand's disease. Coronary atherosclerosis ...

  16. 75 FR 7482 - Submission for OMB Review; Comment Request; The Atherosclerosis Risk in Communities Study (ARIC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-19

    ...Health Submission for OMB Review; Comment Request; The Atherosclerosis Risk in Communities Study (ARIC) Summary: Under the...valid OMB control number. Proposed Collection Title: The Atherosclerosis Risk in Communities Study (ARIC). Type of...

  17. Z39Ig is expressed on macrophages and may mediate inflammatory reactions in arthritis and atherosclerosis

    E-print Network

    Lee, Won-Ha

    and atherosclerosis Min-Young Lee,*, Won-Jung Kim,* Yoon-Joong Kang,* Young-Mi Jung,*, Young-Mo Kang, Kyoungho Suk atherosclerosis. Foam cells, along with endothelial cells and activated smooth muscle cells, are the source

  18. Atherosclerosis 161 (2002) 4554 Anti-atherogenic effects of the acyl-CoA:cholesterol acyltransferase

    E-print Network

    Terasaki, Mark

    2002-01-01

    Atherosclerosis 161 (2002) 45­54 Anti-atherogenic effects of the acyl Science Ireland Ltd. All rights reserved. Keywords: ACAT; Foam cells; Macrophages; Apolipoprotein E www.elsevier.com/locate/atherosclerosis

  19. EXPERIMENTAL ATHEROSCLEROSIS AND BLOOD PRESSURE IN THE RABBIT

    PubMed Central

    Dominguez, R.

    1927-01-01

    1. Van Leersum's range for the normal blood pressure in the rabbit, as recorded by his method, is confirmed. 2. Van Leersum's conclusion concerning the influence of a liver diet on the blood pressure of the rabbit is not substantiated by his data, since the fluctuations of blood pressure he obtained do not surpass his own recorded figures for normal animals. 3. Fluctuations of systolic blood pressure beyond the "normal" range are not necessary for the production of experimental atherosclerosis of the aorta in rabbits. Inversely, egg yolk feeding experiments in rabbits in which atherosclerosis of varying degree, even extreme, is obtained, are not accompanied by an elevation of blood pressure outside the "normal" range. 4. The fluctuations of blood pressure observed during experimental atherosclerosis do not simulate the condition of essential hypertension in man. PMID:19869349

  20. Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis

    SciTech Connect

    Qiao, Wang; Chaoshu, Tang; Key Laboratory of Molecular Cardiovascular Medicine, Ministry of Education ; Hongfang, Jin; Junbao, Du

    2010-05-28

    Atherosclerosis is a chronic, complex, and progressive pathological process in large and medium sized arteries. The exact mechanism of this process remains unclear. Hydrogen sulfide (H{sub 2}S), a novel gasotransmitter, was confirmed as playing a major role in the pathogenesis of many cardiovascular diseases. It plays a role in vascular smooth muscle cell (VSMC) proliferation and apoptosis, participates in the progress of hyperhomocysteinemia (HHCY), inhibits atherogenic modification of LDL, interferes with vascular calcification, intervenes with platelet function, and there are interactions between H{sub 2}S and inflammatory processes. The role of H{sub 2}S in atherosclerotic pathogenesis highlights the mysteries of atherosclerosis and inspires the search for innovative therapeutic strategies. Here, we review the studies to date that have considered the role of H{sub 2}S in atherosclerosis.

  1. Recent insights into the cellular biology of atherosclerosis.

    PubMed

    Tabas, Ira; García-Cardeña, Guillermo; Owens, Gary K

    2015-04-13

    Atherosclerosis occurs in the subendothelial space (intima) of medium-sized arteries at regions of disturbed blood flow and is triggered by an interplay between endothelial dysfunction and subendothelial lipoprotein retention. Over time, this process stimulates a nonresolving inflammatory response that can cause intimal destruction, arterial thrombosis, and end-organ ischemia. Recent advances highlight important cell biological atherogenic processes, including mechanotransduction and inflammatory processes in endothelial cells, origins and contributions of lesional macrophages, and origins and phenotypic switching of lesional smooth muscle cells. These advances illustrate how in-depth mechanistic knowledge of the cellular pathobiology of atherosclerosis can lead to new ideas for therapy. PMID:25869663

  2. Anti-inflammatory therapeutics for the treatment of atherosclerosis

    PubMed Central

    Charo, Israel F.; Taub, Rebecca

    2013-01-01

    Atherosclerosis is the primary cause of heart disease and stroke and is thus the underlying pathology of the leading causes of death in the western world. Although risk can be reduced by lowering lipid levels, the equally important contribution of inflammation to the development of cardiovascular disease is not adequately addressed by existing therapies. Here, we summarize the evidence supporting a role for inflammation in the pathogenesis of atherosclerosis, discuss agents that are currently in the clinic and provide a perspective on the challenges faced in the development of drugs that target vascular inflammation. PMID:21532566

  3. Noninvasive coronary imaging for atherosclerosis in human immunodeficiency virus infection.

    PubMed

    Gharib, Ahmed M; Abd-Elmoniem, Khaled Z; Pettigrew, Roderic I; Hadigan, Colleen

    2011-01-01

    Coronary artery disease is increasingly recognized as an important contributor to morbidity and mortality among persons living with human immunodeficiency virus (HIV) infection. Traditional cardiovascular disease risk factors as well as aspects of HIV infection and its therapy contribute to the increased coronary artery disease observed in HIV. Advances in noninvasive imaging methodologies in both computed tomography and magnetic resonance imaging provide opportunities to evaluate coronary artery atherosclerosis in ways not possible by conventional invasive x-ray angiography. Application of these techniques may prove very useful in the study of atherosclerosis in many diseases, such as HIV. PMID:21939819

  4. Management of radiation-induced accelerated carotid atherosclerosis

    SciTech Connect

    Loftus, C.M.; Biller, J.; Hart, M.N.; Cornell, S.H.; Hiratzka, L.F.

    1987-07-01

    Patients with long survival following cervical irradiation are at risk for accelerated carotid atherosclerosis. The neurologic presentation in these patients mimics naturally occurring atheromatous disease, but patients often present at younger ages and with less concurrent coronary or systemic vascular disease. Hypercholesterolemia also contributes to this accelerated arteriosclerosis. Angiographic findings in this disorder include disproportionate involvement of the distal common carotid artery and unusually long carotid lesions. Pathologic findings include destruction of the internal elastic lamina and replacement of the normal intima and media with fibrous tissue. This article describes two surgical patients with radiation-induced accelerated carotid atherosclerosis who typify the presentation and characteristics of this disease.

  5. Recent insights into the cellular biology of atherosclerosis

    PubMed Central

    García-Cardeña, Guillermo; Owens, Gary K.

    2015-01-01

    Atherosclerosis occurs in the subendothelial space (intima) of medium-sized arteries at regions of disturbed blood flow and is triggered by an interplay between endothelial dysfunction and subendothelial lipoprotein retention. Over time, this process stimulates a nonresolving inflammatory response that can cause intimal destruction, arterial thrombosis, and end-organ ischemia. Recent advances highlight important cell biological atherogenic processes, including mechanotransduction and inflammatory processes in endothelial cells, origins and contributions of lesional macrophages, and origins and phenotypic switching of lesional smooth muscle cells. These advances illustrate how in-depth mechanistic knowledge of the cellular pathobiology of atherosclerosis can lead to new ideas for therapy. PMID:25869663

  6. Changes in transcriptome of macrophages in atherosclerosis

    PubMed Central

    Chistiakov, Dimitry A; Bobryshev, Yuri V; Orekhov, Alexander N

    2015-01-01

    Macrophages display significant phenotypic heterogeneity. Two growth factors, macrophage colony-stimulating factor and chemokine (C-X-C motif) ligand 4, drive terminal differentiation of monocytes to M0 and M4 macrophages respectively. Compared to M0 macrophages, M4 cells have a unique transcriptome, with expression of surface markers such as S100A8, mannose receptor CD206 and matrix metalloproteinase 7. M4 macrophages did not express CD163, a scavenger receptor for haemoglobin/haptoglobin complex. Depending on the stimuli, M0 macrophages could polarize towards the proinflammatory M1 subset by treatment with lipopolysaccharide or interferon-?. These macrophages produce a range of proinflammatory cytokines, nitric oxide, reactive oxygen species and exhibit high chemotactic and phagocytic activity. The alternative M2 type could be induced from M0 macrophage by stimulation with interleukin (IL)-4. M2 macrophages express high levels of CD206 and produce anti-inflammatory cytokines IL-10 and transforming growth factor-?. M1, M2 and M4 macrophages could be found in atherosclerotic plaques. In the plaque, macrophages are subjected to the intensive influence not only by cytokines and chemokines but also with bioactive lipids such as cholesterol and oxidized phospholipids. Oxidized phospholipids induce a distinct Mox phenotype in murine macrophages that express a unique panel of antioxidant enzymes under control of the redox-regulated transcription factor Klf2, resistant to lipid accumulation. In unstable human lesions, atheroprotective M(Hb) and HA-mac macrophage subsets could be found. These two subsets are induced by the haemoglobin/haptoglobin complex, highly express haeme oxygenase 1 and CD163, and are implicated in clearance of haemoglobin and erythrocyte remnants. In atherogenesis, the macrophage phenotype is plastic and could therefore be switched to proinflammatory (i.e. proatherogenic) and anti-inflammatory (i.e. atheroprotective). The aim of this review was to characterize changes in macrophage transcriptome in atherosclerosis and discuss key markers that characterize different phenotypes of macrophages present in atherosclerotic lesions. PMID:25973901

  7. Heme Oxygenase-1, Oxidation, Inflammation, and Atherosclerosis

    PubMed Central

    Araujo, Jesus A.; Zhang, Min; Yin, Fen

    2012-01-01

    Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low-density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1) is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of HO, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide, and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This suggests that a potential intervention on HO-1 or its byproducts may need to take into account any potential alteration in the status of Nrf2 activation. This article reviews the available evidence that supports the antiatherogenic role of HO-1 as well as the potential pathways and mechanisms mediating vascular protection. PMID:22833723

  8. JTT-130, a novel intestine-specific inhibitor of microsomal triglyceride transfer protein, ameliorates lipid metabolism and attenuates atherosclerosis in hyperlipidemic animal models.

    PubMed

    Mera, Yasuko; Kawai, Takashi; Ogawa, Naoto; Odani, Naoya; Sasase, Tomohiko; Miyajima, Katsuhiro; Ohta, Takeshi; Kakutani, Makoto

    2015-11-01

    JTT-130 was developed as an intestine-specific MTP inhibitor designed to rapidly catabolize after absorption to avoid causing hepatotoxicity due to hepatic MTP inhibition. In previous reports, we have demonstrated that JTT-130 suppresses dietary lipid absorption in the small intestine without inducing hepatic steatosis. Thus, in this report, JTT-130 was administered to hyperlipidemic animals fed a Western diet to investigate the effect of intestinal MTP inhibition on lipid metabolism and progression of atherosclerosis. JTT-130 potently lowered plasma non-high density lipoprotein-cholesterol, and elevated plasma high density lipoprotein-cholesterol (HDL-C), indicating improvement in atherogenic index in hamsters. HDL fractions obtained after two weeks treatment with JTT-130 significantly increased the efflux of cholesterol from macrophages, as an index parameter of HDL function. Furthermore, long-term treatment with JTT-130 also improved the plasma lipid profile without inducing hepatic steatosis in rabbits, resulting in the suppression of atherosclerosis formation in aortas. From these results, JTT-130 ameliorates lipid metabolism accompanied with the enhancement of the anti-atherosclerotic function of HDL, and attenuates the progression of atherosclerosis in hyperlipidemic animals. These findings indicate that intestinal MTP inhibition may be atherogenic in vivo and that JTT-130 may be a useful compound for the treatment of dyslipidemia and a potential anti-atherogenic drug. PMID:26598005

  9. Uremia Accelerates both Atherosclerosis and Arterial Calcification in Apolipoprotein E Knockout Mice

    E-print Network

    Angulo,Jesús

    Uremia Accelerates both Atherosclerosis and Arterial Calcification in Apolipoprotein E Knockout, Bronx, New York Chronic renal failure (CRF) favors the development of atherosclerosis and excessive) a possible acceleration of aortic atherosclerosis, (2) the degree and type of vascular calcification, and (3

  10. 75 FR 46945 - Proposed Collection; Comment Request; Multi-Ethnic Study of Atherosclerosis (MESA) Event...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-04

    ... Atherosclerosis (MESA) Event Surveillance SUMMARY: In compliance with the requirement of Section 3506(c)(2)(A) of... Budget (OMB) for review and approval. Proposed Collection: Title: Multi-Ethnic Study of Atherosclerosis... and progression of subclinical cardiovascular disease (CVD)-- that is, atherosclerosis and other...

  11. Engineering Atherosclerosis is the leading cause of death, both above and

    E-print Network

    Chemical Engineering Abstract Atherosclerosis is the leading cause of death, both above and below with atherosclerosis. We also consider manipulation of aquaporin numbers as a strategy to affect disease progression does Aquaporin-1 have to do with early atherosclerosis? Hint: trans-arterial water flow Dr. David

  12. Atherosclerosis 161 (2002) 255260 A novel chemokine, Leukotactin-1, induces chemotaxis,

    E-print Network

    Lee, Won-Ha

    2002-01-01

    Atherosclerosis 161 (2002) 255­260 A novel chemokine, Leukotactin-1, induces chemotaxis, pro-atherogenic cytokines, and tissue factor expression in atherosclerosis Won-Ha Lee a,1 , Se-Hwa Kim a , Euy-Myoung Jeong (MCP) -1 and interleukin (IL)-8 are known to be involved in various processes in atherosclerosis

  13. Atherosclerosis, II (1989) 43-51 Elsevier Scientific Publishers Ireland, Ltd.

    E-print Network

    1989-01-01

    Atherosclerosis, II (1989) 43-51 Elsevier Scientific Publishers Ireland, Ltd. 43 ATH 04300 Limitations of the lipid state hypothesis for atherosclerosis are revealed by X-ray diffraction measurements lesions characteristic of atherosclerosis. We have tested several corollaries suggested by this hypothesis

  14. The Guanine-Nucleotide Exchange Factor SGEF Plays a Crucial Role in the Formation of Atherosclerosis

    E-print Network

    Welch, Greg

    of Atherosclerosis Thomas Samson1. , Jaap D. van Buul2 *. , Jeffrey Kroon2 , Christopher Welch3 , Erik N. Bakker4 of atherosclerosis. Previously, we showed in vitro that the RhoG guanine nucleotide exchange factor SGEF (Arhgef26 a significant decrease in the formation of atherosclerosis in multiple aortic areas. A fluorescent biosensor

  15. Matrix Gla Protein Is Associated With Risk Factors for Atherosclerosis but not With Coronary Artery Calcification

    E-print Network

    Price, Paul A.

    Matrix Gla Protein Is Associated With Risk Factors for Atherosclerosis but not With Coronary Artery in larger populations. (Arterioscler Thromb Vasc Biol. 2006;26:2769-2774.) Key Words: atherosclerosis calcification (CAC) occurs in atherosclerosis1 and is associated with increased risk for coronary heart disease

  16. Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

    PubMed Central

    Ng, Chun-Yi; Jaarin, Kamsiah

    2015-01-01

    Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies. PMID:26064920

  17. Endothelial function and atherosclerosis: circulatory markers with clinical usefulness.

    PubMed

    Ribeiro, Fernando; Alves, Alberto J; Teixeira, Madalena; Ribeiro, Vasco; Duarte, José A; Oliveira, José

    2009-10-01

    The healthy endothelium secretes and expresses at the surface various molecules which help maintain vascular wall structure and vascular homeostasis, as well as regulating vascular tone and leukocyte traffic. In response to various aggressive stimuli, the endothelial cell modulates its properties to restore vascular homeostasis. Usually, changes in the endothelial cell phenotype are transient and do not compromise the subsequent re-establishment of endothelial function. However, in certain pathological conditions, such as atherosclerosis, endothelial function is chronically disturbed, and this alteration is a critical step in the progression of the disease. In recent years, advances in knowledge have improved our understanding of the physiopathology of atherosclerosis, which is now known to be a dynamic and progressive process proceeding from endothelial dysfunction and inflammation of the vascular wall. The evolution and prognosis of atherosclerosis, along with the efficacy of therapeutic modalities, can be assessed by measuring the circulating levels of various biomarkers expressed or released by the endothelium. The purpose of this review is to reappraise the evidene concerning endothelial function under physiological conditions and in atherosclerosis, and to analyze markers of endothelial function with clinical applicability. PMID:20058778

  18. Association between Metabolic Components and Subclinical Atherosclerosis in Korean Adults

    PubMed Central

    Hwang, In Cheol; Seo, Ah-Ram; Ahn, Hong Yup; Yim, Eunji

    2012-01-01

    Background Many studies have attempted to develop relatively simple and easy noninvasive measurements of atherosclerosis (NIMA), and each NIMA assesses different atherosclerotic properties. We, therefore, investigated the association between metabolic syndrome (MetS) components and different NIMAs. Methods This study included 1,132 Korean subjects over 20 years of age who had visited a Health Promotion Center in Korea. Carotid injury (increased carotid intima-media thickness or plaques) was evaluated by ultrasonography and arterial stiffness by brachial-ankle pulse wave velocity. The MetS components were assessed according to the Asian criteria of the American Heart Association/National Heart, Lung, and Blood Institute. Results Both arterial stiffness and carotid injury gradually deteriorated with increase in the number of MetS components. Arterial stiffness and carotid injury were associated with different MetS components, each of which had varying impact. After adjustment for all possible confounders such as age, sex, and lifestyle, elevated blood pressure (BP) was found to have the strongest association with arterial stiffness, whereas central obesity, impaired fasting plasma glucose, and elevated BP had comparable connection with carotid atherosclerosis. Conclusion Individual MetS components were related with subclinical atherosclerosis in different ways. Elevated BP showed the strongest association with arterial stiffness, while central obesity, impaired fasting plasma glucose, and elevated BP showed good correlation with carotid atherosclerosis. PMID:22916325

  19. Cell signaling by reactive nitrogen and oxygen species in atherosclerosis

    NASA Technical Reports Server (NTRS)

    Patel, R. P.; Moellering, D.; Murphy-Ullrich, J.; Jo, H.; Beckman, J. S.; Darley-Usmar, V. M.

    2000-01-01

    The production of reactive oxygen and nitrogen species has been implicated in atherosclerosis principally as means of damaging low-density lipoprotein that in turn initiates the accumulation of cholesterol in macrophages. The diversity of novel oxidative modifications to lipids and proteins recently identified in atherosclerotic lesions has revealed surprising complexity in the mechanisms of oxidative damage and their potential role in atherosclerosis. Oxidative or nitrosative stress does not completely consume intracellular antioxidants leading to cell death as previously thought. Rather, oxidative and nitrosative stress have a more subtle impact on the atherogenic process by modulating intracellular signaling pathways in vascular tissues to affect inflammatory cell adhesion, migration, proliferation, and differentiation. Furthermore, cellular responses can affect the production of nitric oxide, which in turn can strongly influence the nature of oxidative modifications occurring in atherosclerosis. The dynamic interactions between endogenous low concentrations of oxidants or reactive nitrogen species with intracellular signaling pathways may have a general role in processes affecting wound healing to apoptosis, which can provide novel insights into the pathogenesis of atherosclerosis.

  20. Oversized vein grafts develop advanced atherosclerosis in hypercholesterolemic minipigs

    PubMed Central

    2012-01-01

    Background Accelerated atherosclerosis is the main cause of late aortocoronary vein graft failure. We aimed to develop a large animal model for the study of pathogenesis and treatment of vein graft atherosclerosis. Methods An autologous reversed jugular vein graft was inserted end-to-end into the transected common carotid artery of ten hypercholesteroemic minipigs. The vein grafts were investigated 12-14 weeks later with ultrasound and angiograpy in vivo and microscopy post mortem. Results One minipig died during follow up (patent vein graft at autopsy), and one vein graft thrombosed early. In the remaining eight patent vein grafts, the mean (standard deviation) intima-media thickness was 712 ?m (276 ?m) versus 204 ?m (74 ?m) in the contralateral control internal jugular veins (P < .01). Advanced atherosclerotic plaques were found in three of four oversized vein grafts (diameter of graft > diameter of artery). No plaques were found in four non-oversized vein grafts (P < .05). Conclusions Our model of jugular vein graft in the common carotid artery of hypercholesterolemic minipigs displayed the components of human vein graft disease, i.e. thrombosis, intimal hyperplasia, and atherosclerosis. Advanced atherosclerosis, the main cause of late failure of human aortocoronary vein grafts was only seen in oversized grafts. This finding suggests that oversized vein grafts may have detrimental effects on patient outcome. PMID:22463679

  1. New indole-thiazolidine attenuates atherosclerosis in LDLr(-/-) mice.

    PubMed

    César, Fernanda A; Rudnicki, Martina; de Las Heras, Beatriz; Boscá, Lisardo; Lima, Maria C A; Pitta, Ivan R; Abdalla, Dulcineia S P

    2015-08-01

    Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor ? (PPAR?) agonists that improve insulin-mediated glucose uptake and possess beneficial vasculoprotective actions. However, because undesirable side effects are associated with these drugs, novel TZDs are under development. In this study, we evaluated the biological activity of LYSO-7, a new indole-thiazolidine, on PPAR activation, inflammation and atherogenesis using a gene reporter assay, lipopolysaccharide (LPS)-activated RAW 264.7 cell culture, and a low-density lipoprotein receptor knockout (LDLr(-/-)) mouse model of atherosclerosis. LYSO-7 shows low cytotoxicity in RAW 264.7 cells and at 2.5?mol/L induces PPAR? and PPAR? transactivation as well as inhibits LPS-induced nitrite production and the mRNA gene expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1). In addition, treatment with LYSO-7 reduces the development of atherosclerosis in LDLr(-/-) mice, improves the lipid profile, blood glucose levels, and downregulates CD40 and CD40L expression without affecting the body weight of the animals. Altogether, our data show that LYSO-7 possesses anti-inflammatory properties and that treatment with this TZD attenuates atherosclerosis progression in LDLr(-/-) mice by modulating lipid metabolism and inflammation. Thus, LYSO-7 shows potential as a new drug candidate for the treatment of atherosclerosis. PMID:25869519

  2. Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation

    PubMed Central

    Tang, Jun; Lobatto, Mark E.; Hassing, Laurien; van der Staay, Susanne; van Rijs, Sarian M.; Calcagno, Claudia; Braza, Mounia S.; Baxter, Samantha; Fay, Francois; Sanchez-Gaytan, Brenda L.; Duivenvoorden, Raphaël; Sager, Hendrik; Astudillo, Yaritzy M.; Leong, Wei; Ramachandran, Sarayu; Storm, Gert; Pérez-Medina, Carlos; Reiner, Thomas; Cormode, David P.; Strijkers, Gustav J.; Stroes, Erik S.G.; Swirski, Filip K.; Nahrendorf, Matthias; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J.M.

    2015-01-01

    Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E deficient mice (Apoe?/?) with advanced atherosclerotic plaques. This resulted in rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an eight-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis. PMID:26295063

  3. Gradient Echo MRI Characterization of Development of Atherosclerosis in the Abdominal Aorta in Watanabe Heritable Hyperlipidemic Rabbits

    SciTech Connect

    Wang, Yi-Xiang J. Kuribayashi, Hideto; Wagberg, Maria; Holmes, Andrew P.; Tessier, Jean J.; Waterton, John C.

    2006-08-15

    Purpose. The Watanabe Heritable Hyperlipidemic (WHHL) rabbit provides an important model of spontaneous atherosclerosis. With a strain of WHHL rabbits which do not develop abdominal aorta lumen stenosis even with advanced atherosclerosis, we studied the MRI-histology correlation, and the natural progression of atherosclerosis in the abdominal aorta. In addition, intra-reader segmentation repeatability and scan-rescan reproducibility were assessed. Methods. Two batches of female WHHL rabbits were used. The first batch of 6 rabbits was scanned at 20 weeks old. A second batch of 17 rabbits was scanned at 50 weeks old and then randomly divided into two subgroups: 8 were killed for histologic investigation; 9 were kept alive for follow-up, with repeat scanning a week later to assess scan-rescan reproducibility, and again at 73 weeks old to assess disease progression. MR images were acquired at 4.7 T using a chemical shift selective fat suppression gradient echo with a saturation band suppressing blood signal within the aortic lumen. Five slices per animal were acquired, centered around the renal artery region of the abdominal aorta, with in-plane resolution of 0.195 mm and slice thickness of 3 mm. Results. The coefficient of variation for intra-reader reproducibility for aortic wall thickness measurements was 2.5% for repeat segmentations of the same scans on the same day, but segmentations of these same scans made 8 months later showed a systematic change, suggesting that intra-reader bias as well as increased variability could compromise assessments made over time. Comparative analyses were therefore performed in one postprocessing session. The coefficient of variation for scan-rescan reproducibility for aortic wall thickness was 5.5% for nine pairs of scans acquired a week apart and segmented on the same day. Good MRI-histology correlation was obtained. The MRI-measured mean aortic wall thickness of animals at 20 weeks of age was 76% that of animals at 50 weeks of age (p < 0.001). There was a small increase in aortic wall thickness between 50 and 73 weeks of age, but this was not significant (p > 0.05). The corresponding differences in lumen cross-sectional areas at 20, 50, and 73 weeks of age were not significant. These results were consistent with in-house historical histology data on this strain of rabbits. Conclusions. High-resolution gradient echo MRI can follow disease progression in the WHHL rabbit spontaneous atherosclerosis disease model.

  4. Low bone mineral density is associated with intracranial posterior circulation atherosclerosis in women.

    PubMed

    Kang, K

    2015-12-01

    Low bone mineral density (BMD) is associated with carotid atherosclerosis and the incidence of stroke. However, there are no data on the association of BMD with intracranial atherosclerosis. The study population consisted of 357 participants who underwent dual energy x-ray absorptiometric scanning of the lumbar spine and brain 3D time of flight magnetic resonance angiography as part of their voluntary health checks. The basilar, middle cerebral, intracranial internal carotid and intracranial vertebral arteries were evaluated. Low BMD was defined as a T-score of less than -1. All analyses were stratified by sex and intracranial atherosclerosis location. One hundred seventy-six women (53years; 66.9% postmenopausal; 33.5% low BMD; 60.2% intracranial atherosclerosis in the anterior circulation (AC); 60.2% intracranial atherosclerosis in the posterior circulation (PC)) and 181 men (51years; 28.7% low BMD; 61.9% intracranial atherosclerosis in the AC; 55.8% intracranial atherosclerosis in the PC) were included. In women, low BMD was significantly associated with intracranial atherosclerosis in the PC with the odds ratio of 2.57 (95% confidence interval 1.11-5.99). However, intracranial atherosclerosis in the AC was not associated with BMD in women. In men, there were no significant associations between BMD and intracranial atherosclerosis. In conclusion, this study shows that low BMD is associated with subclinical intracranial PC atherosclerosis in women but not in men. PMID:26431918

  5. A novel dilute and shoot HPLC assay method for quantification of irbesartan and hydrochlorothiazide in combination tablets and urine using second generation C18-bonded monolithic silica column with double gradient elution.

    PubMed

    Koyuturk, Sema; Can, Nafiz Oncu; Atkosar, Zeki; Arli, Goksel

    2014-08-01

    Irbesartan (IRB) and hydrochlorothiazide (HCT) are angiotensin-II receptor antagonist and thiazide-class diuretic compounds, respectively, which are in use in the treatment of hypertension. A novel dilute-and-shoot HPLC assay method for simultaneous quantification of IRB and HCT in fixed-dose combination tablets and urine samples was described. The separation of IRB, HCT and agomelatine (internal standard) was carried out using a second generation C18-bonded monolithic silica column (Chromolith(®) High Resolution RP-18e, 100×4.6mm, Merck KGaA), utilizing both mobile phase and flow rate gradient elution programs. The analytes were detected at 230 nm wavelength using photodiode array detector within 24 minutes with high resolution, observing about 50 percent more peak capacity when using second generation C18-bonded monolithic silica column. Urine samples were introduced into the system effortlessly, with only filtration and subsequent dilution. Validation studies were performed according to the official recommendations of USP and ICH, and the developed method was successfully applied to pharmaceutical tablets and urine samples. PMID:24876066

  6. Reduced Acute Vascular Injury and Atherosclerosis in Hyperlipidemic Mice Transgenic for Lysozyme

    PubMed Central

    Liu, Huixian; Zheng, Feng; Li, Zhu; Uribarri, Jaime; Ren, Bin; Hutter, Randolph; Tunstead, James R.; Badimon, Juan; Striker, Gary E.; Vlassara, Helen

    2006-01-01

    Hyperlipidemia promotes oxidant stress, inflammation, and atherogenesis in apolipoprotein E-deficient (ApoE(?/?)) mice. Mice transgenic for lysozyme (LZ-Tg) are resistant to acute and chronic oxidative stress and have decreased circulating levels of pro-oxidant advanced glycation end-products (AGEs). Herein we report that TIB-186 macrophages transduced with adenovirus-expressing human LZ (AdV-LZ) containing the AGE-binding domain facilitated AGE uptake and degradation and that AdV-LZ-transduced macrophages and peritoneal macrophages from LZ-Tg mice suppressed the AGE-triggered tumor necrosis factor-? response. We assessed atherosclerosis in LZ-Tg mice crossed with ApoE(?/?) mice (LZ/ApoE(?/?)) and found increased serum LZ levels and decreased AGE and 8-isoprostanes levels, although hyperlipidemia remained similar to ApoE(?/?) controls. Atherosclerotic plaques and neointimal lesions at the aortic root and descending aorta were markedly decreased (by 40% and 80%, respectively) in LZ/ApoE(?/?) versus ApoE(?/?) mice, as were inflammatory infiltrates. The arterial lesions following femoral artery injury in LZ/ApoE(?/?) mice were suppressed (intimal to media ratio decreased by 50%), as were AGE deposits and vascular smooth muscle cell activation, compared to ApoE(?/?) mice. Despite hyperlipidemia, development of atheroma and occlusive, inflammatory arterial neointimal lesions in response to injury was suppressed in LZ/ApoE(?/?) mice. This effect may be due to the antioxidant properties of LZ, which is possibly linked to the AGE-binding domain region of the molecule. PMID:16816382

  7. Large animal models of atherosclerosis - new tools for persistent problems in cardiovascular medicine.

    PubMed

    Shim, J; Al-Mashhadi, R H; Sørensen, C B; Bentzon, J F

    2016-01-01

    Coronary heart disease and ischaemic stroke caused by atherosclerosis are leading causes of illness and death worldwide. Small animal models have provided insight into the fundamental mechanisms driving early atherosclerosis, but it is increasingly clear that new strategies and research tools are needed to translate these discoveries into improved prevention and treatment of symptomatic atherosclerosis in humans. Key challenges include better understanding of processes in late atherosclerosis, factors affecting atherosclerosis in the coronary bed, and the development of reliable imaging biomarker tools for risk stratification and monitoring of drug effects in humans. Efficient large animal models of atherosclerosis may help tackle these problems. Recent years have seen tremendous advances in gene-editing tools for large animals. This has made it possible to create gene-modified minipigs that develop atherosclerosis with many similarities to humans in terms of predilection for lesion sites and histopathology. Together with existing porcine models of atherosclerosis that are based on spontaneous mutations or severe diabetes, such models open new avenues for translational research in atherosclerosis. In this review, we discuss the merits of different animal models of atherosclerosis and give examples of important research problems where porcine models could prove pivotal for progress. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26414760

  8. Activation of the human terminal complement pathway in atherosclerosis.

    PubMed

    Niculescu, F; Rus, H G; Vlaicu, R

    1987-11-01

    The presence of the terminal C5b-9 complement complex in tissues indicates that complement activation has occurred in situ with subsequent membrane damage, tissue injury, and inflammatory response mediation. The terminal C5b-9 neoantigens of the complement system, S protein C3c, C3d, and apolipoprotein B deposits were localized in 20 aortic fibrous plaques, 12 aortic intimal thickenings, 8 aortic fatty streak intimae, 14 coronary fibrous plaques, 5 coronary intimal thickenings, and 8 femoral fibrous plaques, using an indirect and double-staining immunoperoxidase technique. The specific granular deposits were present from the early to the advanced stages of atherosclerosis in relation to the degree of fibrosis and necrosis. The different double-staining localization of C5b-9 and S protein may suggest local assembly of the complex as a consequence of complement activation and may sustain its role in the chronic progression of atherosclerosis. PMID:2444373

  9. Intravascular multispectral optoacoustic tomography of atherosclerosis: prospects and challenges

    PubMed Central

    Rosenthal, Amir; Jaffer, Farouc A; Ntziachristos, Vasilis

    2012-01-01

    The progression of atherosclerosis involves complex changes in the structure, composition and biology of the artery wall. Currently, only anatomical plaque burden is routinely characterized in living patients, whereas compositional and biological changes are mostly inaccessible. However, anatomical imaging alone has proven to be insufficient for accurate diagnostics of the disease. Multispectral optoacoustic tomography offers complementary data to anatomical methods and is capable of imaging both tissue composition and, via the use of molecular markers, the biological activity therein. In this paper we review recent progress in multispectral optoacoustic tomography imaging of atherosclerosis with specific emphasis on intravascular applications. The potential capabilities of multispectral optoacoustic tomography are compared with those of established intravascular imaging techniques and current challenges on the road towards a clinically viable imaging modality are discussed. PMID:23144663

  10. Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice

    PubMed Central

    Spolitu, Stefano; Milton, Jaclyn; Ghorpade, Devram; Chiasson, Raymond; Kuriakose, George; Perretti, Mauro; Farokzhad, Omid; Tabas, Ira

    2015-01-01

    Chronic, nonresolving inflammation is a critical factor in the clinical progression of advanced atherosclerotic lesions. In the normal inflammatory response, resolution is mediated by several agonists, among which is the glucocorticoid-regulated protein called annexin A1. The proresolving actions of annexin A1, which are mediated through its receptor N-formyl peptide receptor 2 (FPR2/ALX), can be mimicked by an amino-terminal peptide encompassing amino acids 2–26 (Ac2-26). Collagen IV (Col IV)–targeted nanoparticles (NPs) containing Ac2-26 were evaluated for their therapeutic effect on chronic, advanced atherosclerosis in fat-fed Ldlr?/? mice. When administered to mice with preexisting lesions, Col IV–Ac2-26 NPs were targeted to lesions and led to a marked improvement in key advanced plaque properties, including an increase in the protective collagen layer overlying lesions (which was associated with a decrease in lesional collagenase activity), suppression of oxidative stress, and a decrease in plaque necrosis. In mice lacking FPR2/ALX in myeloid cells, these improvements were not seen. Thus, administration of a resolution-mediating peptide in a targeted NP activates its receptor on myeloid cells to stabilize advanced atherosclerotic lesions. These findings support the concept that defective inflammation resolution plays a role in advanced atherosclerosis, and suggest a new form of therapy. PMID:25695999

  11. Micronutrient concentrations and subclinical atherosclerosis in adults with HIV123

    PubMed Central

    Mangili, Alexandra; Tang, Alice M; Jones, Clara Y; Woods, Margo N; Polak, Joseph F; Wanke, Christine A

    2010-01-01

    Background: Extremes in micronutrient intakes are common in HIV-infected patients in developed countries and may affect the progression of atherosclerosis in this population. Objective: We completed a cross-sectional study examining the association between serum micronutrient concentrations and surrogate markers of atherosclerosis in a cohort of HIV-infected adults. Design: We measured serum selenium, zinc, vitamin A, and vitamin E concentrations as well as carotid intima-media thickness (c-IMT) and coronary artery calcium (CAC) in 298 Nutrition for Healthy Living participants. We assessed cardiovascular disease risk factors, c-IMT, and CAC for each micronutrient tertile by using a chi-square test for binary variables and analysis of variance for continuous variables. We performed multivariate regression of c-IMT and CAC with each micronutrient with adjustment for HIV-related and cardiovascular disease risk factors. Results: In the multivariate analysis, the highest tertile of serum vitamin E concentration was associated with higher common and internal c-IMT and CAC scores (P < 0.05 for c-IMT and CAC). Participants with higher vitamin E concentrations were more likely to have detectable CAC (50% compared with 44% compared with 67% for tertiles 1, 2, and 3, respectively; P = 0.004) and common c-IMT >0.8 mm (5% compared with 4% compared with 17% for tertiles 1, 2, and 3, respectively; P = 0.002). Other than vitamin E, micronutrients had no association with markers of atherosclerosis. Conclusions: Our study showed that elevated serum vitamin E concentrations are associated with abnormal markers of atherosclerosis and may increase the risk of cardiovascular complications in HIV-infected adults. PMID:20219956

  12. Atherosclerosis in young Brazilians suffering violent deaths: a pathological study

    PubMed Central

    2011-01-01

    Background Atherosclerosis is the leading cause of coronary heart disease and ischemic stroke, which can cause sudden death in adulthood. In general, the clinical manifestations of cardiovascular diseases are caused by atherosclerosis, which is a process that starts during middle age. More recent studies indicate that the atherosclerotic process begins during childhood. Methods To evaluate the extent of atherosclerotic disease in young Brazilians, we conducted a study of the pathological alterations in the major arteries of victims of violent death. Samples of the right carotid artery, left coronary artery, and thoracic aorta of young victims of violent death were analyzed and graded in accordance with the histological atherosclerotic lesion types proposed by the American Heart Association. Samples were collected from 100 individuals who had died from external causes, aged from 12 to 33 years. Results The majority of cases (83%) were male, and 66% of deaths were homicides caused by firearms. The median age was 20.0 years and mean body mass index was 20.9 kg/m2. Of the right carotid artery specimens, 3% were normal, 55% had type I, 40% had type II, 1% had type III, and 1% had type IV atherosclerotic lesions. Of the left coronary artery specimens, 5% were normal, 48% had type I, 41% had type II, 3% had type III, and 3% had type IV lesions. Of the thoracic aorta specimens, none were normal, 13% had type I, 64% had type II, 22% had type III, and 1% had type IV lesions. Overall, 97.34% of arteries examined had some degree of atherosclerosis. The most common histological type was type II (foam cells). No thoracic aorta specimens were normal, and the coronary artery specimens had the most atherosclerosis. Conclusions Our results show a high prevalence of atherosclerotic lesions among young people in Brazil. Intervention should be undertaken to decrease the rate of sudden cardiac death in the adult population. PMID:22152277

  13. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis

    PubMed Central

    Husain, Kazim; Hernandez, Wilfredo; Ansari, Rais A; Ferder, Leon

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin II (Ang II) and a decrease in nitric oxide. The renin-angiotensin system (RAS), and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors (angiotensin-converting enzyme inhibitors)], Ang II receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in ApoE-deficient atherosclerotic mice. PMID:26322175

  14. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis.

    PubMed

    Husain, Kazim; Hernandez, Wilfredo; Ansari, Rais A; Ferder, Leon

    2015-08-26

    Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin II (Ang II) and a decrease in nitric oxide. The renin-angiotensin system (RAS), and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors (angiotensin-converting enzyme inhibitors)], Ang II receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in ApoE-deficient atherosclerotic mice. PMID:26322175

  15. Numerical and analytical study of an atherosclerosis inflammatory disease model.

    PubMed

    Hidalgo, A; Tello, L; Toro, E F

    2014-06-01

    We study a reaction-diffusion mathematical model for the evolution of atherosclerosis as an inflammation process by combining analytical tools with computer-intensive numerical calculations. The computational work involved the calculation of more than sixty thousand solutions of the full reaction-diffusion system and lead to the complete characterisation of the ?-limit for every initial condition. Qualitative properties of the solution are rigorously proved, some of them hinted at by the numerical study. PMID:23719743

  16. Epicardial adipose excision slows the progression of porcine coronary atherosclerosis

    PubMed Central

    2014-01-01

    Background In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden. We tested the hypothesis that EAT contributes locally to CAD in a pig model. Methods Ossabaw miniature swine (n?=?9) were fed an atherogenic diet for 6 months to produce CAD. A 15 mm length by 3–5 mm width coronary EAT (cEAT) resection was performed over the middle segment of the left anterior descending artery (LAD) 15 mm distal to the left main bifurcation. Pigs recovered for 3 months on atherogenic diet. Intravascular ultrasound (IVUS) was performed in the LAD to quantify atheroma immediately after adipectomy and was repeated after recovery before sacrifice. Coronary wall biopsies were stained immunohistochemically for atherosclerosis markers and cytokines and cEAT was assayed for atherosclerosis-related genes by RT-PCR. Total EAT volume was measured by non-contrast CT before each IVUS. Results Circumferential plaque length increased (p?atherosclerosis. PMID:24387639

  17. Advances in imaging angiogenesis and inflammation in atherosclerosis

    PubMed Central

    Zagorchev, Lyubomir; Mulligan-Kehoe, Mary Jo

    2013-01-01

    Summary Advances in imaging technology have provided powerful tools for dissecting the angiogenic and inflammatory aspects of atherosclerosis. Improved technology along with multi-modal approaches has expanded the utilisation of imaging. Recent advances provide the ability to better define structure and development of angiogenic vessels, identify relationships between inflammatory mediators and the vessel wall, validate biological effects of anti-inflammatory and anti-angiogenic drugs, delivery and/or targeting specific molecules to inflammatory regions of atherosclerotic plaques. PMID:21331441

  18. Bisphenol A Exposure Enhances Atherosclerosis in WHHL Rabbits

    PubMed Central

    Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

    2014-01-01

    Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

  19. Lasting monitoring of immune state in patients with coronary atherosclerosis

    NASA Astrophysics Data System (ADS)

    Malinova, Lidia I.; Denisova, Tatyana P.; Tuchin, Valery V.

    2007-02-01

    Immune state monitoring is an expensive, invasive and sometimes difficult necessity in patients with different disorders. Immune reaction dynamics study in patients with coronary atherosclerosis provides one of the leading components to complication development, clinical course prognosis and treatment and rehabilitation tactics. We've chosen intravenous glucose injection as metabolic irritant in the following four groups of patients: men with proved coronary atherosclerosis (CA), non insulin dependent diabetes mellitus (NIDDM), men hereditary burden by CA and NIDDM and practically healthy persons with longlivers in generation. Immune state parameters such as quantity of leukocytes and lymphocytes, circulating immune complexes levels, serum immunoglobulin levels, HLA antigen markers were studied at 0, 30 and 60 minutes during glucose loading. To obtain continues time function of studied parameters received data were approximated by polynomials of high degree with after going first derivatives. Time functions analyze elucidate principally different dynamics studied parameters in all chosen groups of patients, which couldn't be obtained from discontinuous data compare. Leukocyte and lymphocyte levels dynamics correlated HLA antigen markers in all studied groups. Analytical estimation of immune state in patients with coronary atherosclerosis shows the functional "margin of safety" of immune system state under glucose disturbance. Proposed method of analytical estimation also can be used in immune system monitoring in other groups of patients.

  20. Mineralocorticoid Receptors in the Pathophysiology of Vascular Inflammation and Atherosclerosis

    PubMed Central

    Moss, Mary E.; Jaffe, Iris Z.

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease of the vasculature that causes significant morbidity and mortality from myocardial infarction, stroke, and peripheral vascular disease. Landmark clinical trials revealed that mineralocorticoid receptor (MR) antagonists improve outcomes in cardiovascular patients. Conversely, enhanced MR activation by the hormone aldosterone is associated with increased risk of MI, stroke, and cardiovascular death. This review summarizes recent advances in our understanding of the role of aldosterone and the MR in the pathogenesis of vascular inflammation and atherosclerosis as it proceeds from risk factor-induced endothelial dysfunction and inflammation to plaque formation, progression, and ultimately rupture with thrombosis, the cause of acute ischemia. The role of the MR in converting cardiac risk factors into endothelial dysfunction, in enhancing leukocyte adhesion and infiltration into the vasculature, in promoting systemic inflammation and vascular oxidative stress, and in plaque destabilization and thrombosis are discussed. A greater understanding of the mechanisms by which the MR promotes atherosclerosis has substantial potential to identify novel treatment targets to improve cardiovascular health and decrease mortality. PMID:26441842

  1. Dexamethasone suppression test

    MedlinePLUS

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

  2. Habitual fish intake and clinically silent carotid atherosclerosis

    PubMed Central

    2014-01-01

    Background Fish consumption is recommended as part of a healthy diet. However, there is a paucity of data concerning the relation between fish consumption and carotid atherosclerosis. We investigated the association between habitual fish consumption and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness (? 0.90 mm), in non-diabetic participants. Methods Nine hundred-sixty-one (range of age: 18–89 yrs; 37.1% males) adult participants without clinically known atherosclerotic disease were randomly recruited among the customers of a shopping mall in Palermo, Italy, and cross-sectionally investigated. Each participant answered a food frequency questionnaire and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Routine laboratory blood measurements were obtained in a subsample of 507 participants. Results Based on habitual fish consumption, participants were divided into three groups: non-consumers or consumers of less than 1 serving a week (24.0%), consumers of 1 serving a week (38.8%), and consumers of???2 servings a week (37.2%). Age-adjusted prevalence of carotid atherosclerosis (presence of plaques or intima media thickness???0.9 mm) was higher in the low fish consumption group (13.3%, 12.1% and 6.6%, respectively; P?=?0.003). Multivariate analysis evidenced that carotid atherosclerosis was significantly associated with age (OR?=?1.12; 95% CI?=?1.09-1.14), hypertension on pharmacologic treatment (OR?=?1.81; 95% CI?=?1.16-2.82), and pulse pressure (OR?=?1.03; 95% CI?=?1.01-1.04), while consuming ?2 servings of fish weekly was protective compared with the condition of consumption of <1 serving of fish weekly (OR?=?0.46; 95% CI?=?0.26-0.80). Conclusions High habitual fish consumption seems to be associated with less carotid atherosclerosis, though adequate interventional trials are necessary to confirm the role of fish consumption in prevention of cardiovascular disease. PMID:24405571

  3. Why did ancient people have atherosclerosis?: from autopsies to computed tomography to potential causes.

    PubMed

    Thomas, Gregory S; Wann, L Samuel; Allam, Adel H; Thompson, Randall C; Michalik, David E; Sutherland, M Linda; Sutherland, James D; Lombardi, Guido P; Watson, Lucia; Cox, Samantha L; Valladolid, Clide M; Abd El-Maksoud, Gomaa; Al-Tohamy Soliman, Muhammad; Badr, Ibrahem; el-Halim Nur el-Din, Abd; Clarke, Emily M; Thomas, Ian G; Miyamoto, Michael I; Kaplan, Hillard S; Frohlich, Bruno; Narula, Jagat; Stewart, Alexandre F R; Zink, Albert; Finch, Caleb E

    2014-06-01

    Computed tomographic findings of atherosclerosis in the ancient cultures of Egypt, Peru, the American Southwest and the Aleutian Islands challenge our understanding of the fundamental causes of atherosclerosis. Could these findings be true? Is so, what traditional risk factors might be present in these cultures that could explain this apparent paradox? The recent computed tomographic findings are consistent with multiple autopsy studies dating as far back as 1852 that demonstrate calcific atherosclerosis in ancient Egyptians and Peruvians. A nontraditional cause of atherosclerosis that could explain this burden of atherosclerosis is the microbial and parasitic inflammatory burden likely to be present in ancient cultures inherently lacking modern hygiene and antimicrobials. Patients with chronic systemic inflammatory diseases of today, including systemic lupus erythematosus, rheumatoid arthritis, and human immunodeficiency virus infection, experience premature atherosclerosis and coronary events. Might the chronic inflammatory load of ancient times secondary to infection have resulted in atherosclerosis? Smoke inhalation from the use of open fires for daily cooking and illumination represents another potential cause. Undiscovered risk factors could also have been present, potential causes that technologically cannot currently be measured in our serum or other tissue. A synthesis of these findings suggests that a gene-environmental interplay is causal for atherosclerosis. That is, humans have an inherent genetic susceptibility to atherosclerosis, whereas the speed and severity of its development are secondary to known and potentially unknown environmental factors. PMID:25667093

  4. Non-invasive ultrasound monitoring of regional carotid wall structure and deformation in atherosclerosis

    E-print Network

    Chan, Raymond C

    2001-01-01

    Atherosclerosis is characterized by local remodeling of arterial structure and distensibility. Developing lesions either progress gradually to compromise tissue perfusion or rupture suddenly to cause catastrophic myocardial ...

  5. Bastadins, brominated-tyrosine derivatives, suppress accumulation of cholesterol ester in macrophages.

    PubMed

    Eguchi, Keisuke; Kato, Hikaru; Fujiwara, Yukio; Losung, Fitje; Mangindaan, Remy E P; de Voogd, Nicole J; Takeya, Motohiro; Tsukamoto, Sachiko

    2015-11-15

    The formation of foam cells in macrophages has been suggested to play an essential role in the progression of early atherosclerotic lesions in vivo and, thus, its suppression is considered to be one of the major approaches for the treatment of atherosclerosis. We isolated eight brominated-tyrosine derivatives, bastadins, from the EtOH extract of the marine sponge Ianthella vasta as inhibitors of the formation of foam cells induced by acetylated low-density lipoproteins in human monocyte-derived macrophages. Bastadin 6 was the strongest inhibitor of foam cell formation due to its suppression of acyl-coenzyme A:cholesterol acyltransferase. PMID:26403929

  6. Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment

    PubMed Central

    Garetto, Stefano; Trovato, Anna Elisa; Lleo, Ana; Sala, Federica; Martini, Elisa; Betz, Alexander G.; Norata, Giuseppe D.; Invernizzi, Pietro; Kallikourdis, Marinos

    2015-01-01

    Regulatory T cells (Treg) influence the development of autoimmunity and their use is increasingly proposed for clinical applications. The well-characterized suppressive potential of Treg frequently leads to the assumption that Treg presence in prevailing numbers is indicative of immunosuppression. We hypothesized that this assumption may be false. We examined models of three different diseases caused by organ-specific autoimmune responses: primary biliary cirrhosis, atherosclerosis and rheumatoid arthritis (RA). We examined indicators of relative abundance of Treg compared to pro-inflammatory T cells, during peak inflammation. In all cases, the results were compatible with a relative enrichment of Treg at the site of inflammation or its most proximal draining lymph node. Conversely, in healthy mice or mice successfully protected from disease via a Treg-mediated mechanism, the data did not suggest that any Treg accumulation was occurring. This counter-intuitive finding may appear to be at odds with the immunosuppressive nature of Treg. Yet extensive previous studies in RA show that an accumulation of Treg occurs at peak inflammation, albeit without resulting in suppression, as the Treg suppressive function is overcome by the cytokine-rich environment. We suggest that this is a ubiquitous feature of autoimmune inflammation. Treg abundance in patient samples is increasingly used as an indicator of a state of immunosuppression. We conclude that this strategy should be revisited as it may potentially be a source of misinterpretation. PMID:25770018

  7. Ultrasound Biomicroscopic Imaging for Interleukin-1 Receptor Antagonist–Inhibiting Atherosclerosis and Markers of Inflammation in Atherosclerotic Development in Apolipoprotein-E Knockout Mice

    PubMed Central

    Li, Rong-Juan; Sun, Yan; Wang, Qin; Yang, Jiao; Song, Li; Wang, Zheng; Luo, Xiang-Hong; Su, Rui-Juan

    2015-01-01

    We sought to validate the hypothesis that the development of atherosclerosis can be suppressed by the interleukin-1 receptor antagonist (IL-1Ra) in murine models of atherosclerosis in vivo, noninvasively seen by means of high-resolution ultrasound biomicroscopy, and we studied changes in inflammatory markers such as IL-1 and C-reactive protein (CRP) plasma levels in these models of atherosclerosis. We divided IL-1Ra+/?/apolipoprotein-E (apoE)?/? and IL-1Ra+/+/apoE?/? mice into 2 age groups, used as atherosclerotic models. The control groups were age-matched IL-1Ra+/+/apoE+/+ mice. Plaque thickness was measured in the ascending aorta in short-axis images by means of ultrasound and histology. Plasma levels of IL-1 and CRP were quantified in the 3 murine groups. At 16 weeks, plaque thickness in the ascending aortas of the IL-1Ra+/?/apoE?/? mice was significantly greater than that in the IL-1Ra+/+/apoE?/? mice, on ultrasound and histology (P <0.01). In contrast, at 32 weeks, the differences between these 2 genotypes were not statistically significant. Serum IL-1 levels were lower in the IL-1Ra+/?/apoE?/? mice than in the IL-1Ra+/+/apoE?/? mice at 16 and 32 weeks (P <0.05). At 16 weeks, serum CRP levels in the IL-1Ra+/?/apoE?/? mice were higher than in the IL-1Ra+/+/apoE?/? mice (P <0.01). Our results suggest that ultrasound biomicroscopy enables evaluation of atherosclerotic lesions in vivo, noninvasively and in real-time, in apoE?/? mice. Partial IL-1Ra deficiencies might promote early plaque development in 16-week-old apoE?/? mice. The balance of IL-1 and IL-1Ra might influence atherosclerotic development. Finally, CRP might affect the initiation of atherosclerosis, rather than its progression. PMID:26413013

  8. Effect of S-aspirin, a novel hydrogen-sulfide-releasing aspirin (ACS14), on atherosclerosis in apoE-deficient mice.

    PubMed

    Zhang, Huili; Guo, Changfa; Zhang, Alian; Fan, Yuqi; Gu, Ting; Wu, Duojiao; Sparatore, Anna; Wang, Changqian

    2012-12-15

    Hydrogen sulfide (H(2)S) is a novel gaseous mediator that plays important roles in atherosclerosis. The present study investigated the effect of a novel H(2)S-releasing aspirin, ACS14 (2-acetyloxybenzoic acid 4-(3-thioxo-3H-1,2-dithiol-5-yl)phenyl ester), on atherosclerotic plaques in fat-fed apoE(-/-) mice and the underlying mechanism with respect to CX3C chemokine receptor 1 (CX3CR1) in macrophages. Mouse macrophage cell line RAW264.7 or mouse peritoneal macrophages were preincubated with aspirin (50, 100 or 200?M), ACS14 (50, 100 or 200?M) or vehicle for 6h, and then stimulated with interferon (IFN)-? (500U/ml) or lipopolysaccharide (LPS; 10?g/ml) for 12h. ACS14, but not aspirin, dose-dependently inhibited IFN-? or LPS-induced CX3CR1 expression and CX3CR1-mediated chemotaxis in macrophages. The inhibitory effect of ACS14 on CX3CR1 expression was abolished by pretreatment with GW9662, a selective peroxisome proliferator-activated receptor (PPAR)-? antagonist, suggesting that suppression of macrophage CX3CR1 expression by ACS14 is PPAR-? dependent. Eight-week-old male apoE(-/-) mice received intraperitoneal ACS14 (15 or 30?mol/kg/day) or aspirin (15 or 30?mol/kg/day) 4 weeks after fat feeding. Twelve weeks after ACS14 or aspirin treatment, mice were sacrificed to evaluate the extent of atherosclerosis and CX3CR1 expression in brachiocephalic artery (BCA). We found that ACS14, but not aspirin, significantly downregulated CX3CR1 expression in atherosclerotic plaques. ACS14 considerably impeded the formation and development of atherosclerosis as compared to a molar equivalent dose of aspirin. These data indicate that ACS14 may prevent the progression of atherosclerosis by downregulating macrophage CX3CR1 expression via a PPAR-?-dependent mechanism. PMID:23085268

  9. MafB promotes atherosclerosis by inhibiting foam-cell apoptosis

    NASA Astrophysics Data System (ADS)

    Hamada, Michito; Nakamura, Megumi; Tran, Mai Thi Nhu; Moriguchi, Takashi; Hong, Cynthia; Ohsumi, Takayuki; Dinh, Tra Thi Huong; Kusakabe, Manabu; Hattori, Motochika; Katsumata, Tokio; Arai, Satoko; Nakashima, Katsuhiko; Kudo, Takashi; Kuroda, Etsushi; Wu, Chien-Hui; Kao, Pei-Han; Sakai, Masaharu; Shimano, Hitoshi; Miyazaki, Toru; Tontonoz, Peter; Takahashi, Satoru

    2014-01-01

    MafB is a transcription factor that induces myelomonocytic differentiation. However, the precise role of MafB in the pathogenic function of macrophages has never been clarified. Here we demonstrate that MafB promotes hyperlipidemic atherosclerosis by suppressing foam-cell apoptosis. Our data show that MafB is predominantly expressed in foam cells found within atherosclerotic lesions, where MafB mediates the oxidized LDL-activated LXR/RXR-induced expression of apoptosis inhibitor of macrophages (AIM). In the absence of MafB, activated LXR/RXR fails to induce the expression of AIM, a protein that is normally responsible for protecting macrophages from apoptosis; thus, Mafb-deficient macrophages are prone to apoptosis. Haematopoietic reconstitution with Mafb-deficient fetal liver cells in recipient LDL receptor-deficient hyperlipidemic mice revealed accelerated foam-cell apoptosis, which subsequently led to the attenuation of the early atherogenic lesion. These findings represent the first evidence that the macrophage-affiliated MafB transcription factor participates in the acceleration of atherogenesis.

  10. Biomarkers of Cardiovascular Stress and Subclinical Atherosclerosis in the Community

    PubMed Central

    Gopal, Deepa M.; Larson, Martin G.; Januzzi, James L.; Cheng, Susan; Ghorbani, Anahita; Wollert, Kai C.; Kempf, Tibor; D'Agostino, Ralph B.; Polak, Joseph F.; Ramachandran, Vasan S.; Wang, Thomas J.; Ho, Jennifer E.

    2014-01-01

    BACKGROUND Biomarkers of cardiovascular stress have been associated with incident cardiovascular outcomes. Their relations with measures of subclinical atherosclerosis, as assessed by carotid intima-media thickness, have not been well described. METHODS Plasma growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) were measured in 3111 Framingham Offspring participants who also underwent carotid ultrasonography during the sixth examination (1995 – 1998, mean age 58 years, 54% women). Carotid measurements included maximal internal carotid artery (ICA) intima-media thickness (IMT), plaque presence (defined as ICA IMT > 1.5 mm), and mean common carotid artery IMT. Multivariable regressions for carotid measurements versus biomarkers were carried out using linear and logistic models; P < 0.0056 was deemed statistically significant. RESULTS Maximal ICA IMT was significantly associated with plasma GDF-15 (?-estimate 0.04 per 1 unit increase in log-GDF-15 SE 0.01, P < 0.0001). Similarly, the odds of having carotid plaque increased 33% (OR 1.33 per 1-unit increase in log-GDF-15, 95% CI 1.20-1.48, P < 0.0001). In contrast, there was no significant association of maximal ICA IMT or plaque presence with sST2 or hsTnI, and none of the three biomarkers was significantly associated with mean CCA IMT. GDF-15 was a stronger predictor of maximal ICA thickness and plaque presence compared with BNP and CRP when these conventional biomarkers were tested together. CONCLUSION Higher GDF-15 concentrations are associated with subclinical atherosclerosis, including maximal ICA IMT and carotid plaque presence. Future studies investigating the role of GDF-15 for screening and management of patients with subclinical atherosclerosis are warranted. PMID:25237063

  11. STAT4 deficiency reduces the development of atherosclerosis in mice.

    PubMed

    Taghavie-Moghadam, Parésa L; Gjurich, Breanne N; Jabeen, Rukhsana; Krishnamurthy, Purna; Kaplan, Mark H; Dobrian, Anca D; Nadler, Jerry L; Galkina, Elena V

    2015-11-01

    Atherosclerosis is a chronic inflammatory process that leads to plaque formation in large and medium sized vessels. T helper 1 (Th1) cells constitute the majority of plaque infiltrating pro-atherogenic T cells and are induced via IFN?-dependent activation of T-box (Tbet) and/or IL-12-dependent activation of signal transducer and activator of transcription 4 (STAT4). We thus aimed to define a role for STAT4 in atherosclerosis. STAT4-deficiency resulted in a ?71% reduction (p < 0.001) in plaque burden in Stat4(-/-)Apoe(-/-) vs Apoe(-/-) mice fed chow diet and significantly attenuated atherosclerosis (?31%, p < 0.01) in western diet fed Stat4(-/-)Apoe(-/-) mice. Surprisingly, reduced atherogenesis in Stat4(-/-)Apoe(-/-) mice was not due to attenuated IFN? production in vivo by Th1 cells, suggesting an at least partially IFN?-independent pro-atherogenic role of STAT4. STAT4 is expressed in T cells, but also detected in macrophages (M?s). Stat4(-/-)Apoe(-/-)in vitro differentiated M1 or M2 M?s had reduced cytokine production compare to Apoe(-/-) M1 and M2 M?s that was accompanied by reduced induction of CD69, I-A(b), and CD86 in response to LPS stimulation. Stat4(-/-)Apoe(-/-) M?s expressed attenuated levels of CCR2 and demonstrated reduced migration toward CCL2 in a transwell assay. Importantly, the percentage of aortic CD11b(+)F4/80(+)Ly6C(hi) M?s was reduced in Stat4(-/-)Apoe(-/-) vs Apoe(-/-) mice. Thus, this study identifies for the first time a pro-atherogenic role of STAT4 that is at least partially independent of Th1 cell-derived IFN?, and primarily involving the modulation of M? responses. PMID:26386214

  12. Splenocytes Seed Bone Marrow of Myeloablated Mice: Implication for Atherosclerosis

    PubMed Central

    Wang, Lai; Yang, Mingjie; Arias, Ana; Song, Lei; Li, Fuqiang; Tian, Fang; Qin, Minghui; Yukht, Ada; Williamson, Ian K.; Shah, Prediman K.; Sharifi, Behrooz G.

    2015-01-01

    Extramedullary hematopoiesis has been shown to contribute to the pathogenesis of a variety of diseases including cardiovascular diseases. In this process, the spleen is seeded with mobilized bone marrow cells that augment its hematopoietic ability. It is unclear whether these immigrant cells that are produced/reprogrammed in spleen are similar or different from those found in the bone marrow. To begin to understand this, we investigated the relative potency of adult splenocytes per se to repopulate bone marrow of lethally-irradiated mice and its functional consequences in atherosclerosis. The splenocytes were harvested from GFP donor mice and transplanted into myeloablated wild type recipient mice without the inclusion of any bone marrow helper cells. We found that adult splenocytes repopulated bone marrow of myeloablated mice and the transplanted cells differentiated into a full repertoire of myeloid cell lineages. The level of monocytes/macrophages in the bone marrow of recipient mice was dependent on the cell origin, i.e., the donor splenocytes gave rise to significantly more monocytes/macrophages than the donor bone marrow cells. This occurred despite a significantly lower number of hematopoietic stem cells being present in the donor splenocytes when compared with donor bone marrow cells. Atherosclerosis studies revealed that donor splenocytes displayed a similar level of atherogenic and atheroprotective activities to those of donor bone marrow cells. Cell culture studies showed that the phenotype of macrophages derived from spleen is different from those of bone marrow. Together, these results demonstrate that splenocytes can seed bone marrow of myeloablated mice and modulate atherosclerosis. In addition, our study shows the potential of splenocytes for therapeutic interventions in inflammatory disease. PMID:26038819

  13. Carotid Atherosclerosis and 10-year Changes in Cognitive Function

    PubMed Central

    Zhong, Wenjun; Cruickshanks, Karen J; Schubert, Carla R; Acher, Charles W; Carlsson, Cynthia M; Klein, Barbara EK; Klein, Ronald; Chappell, Richard J

    2012-01-01

    Background Carotid atherosclerosis has been suggested to be involved in cognitive decline. Methods The Epidemiology of Hearing Loss Study is a longitudinal study of aging among Beaver Dam residents, WI. In 1998–2000, carotid intima-media thickness (IMT) and plaque were measured by ultrasound; cognitive function was measured by the Mini-Mental State Examination (MMSE). Follow-up examinations were conducted in 2003–2005 and 2009–2010. Incidence of cognitive impairment was defined as a MMSE score <24 or reported physician-diagnosed dementia during the follow-up. In the last examination, five additional cognitive tests were added. The associations of carotid atherosclerosis with incident cognitive impairment and cognitive test performance ten years later were evaluated. Results A total of 1651 participants (mean age 66.8 years, 41% men) without cognitive impairment at baseline were included in the incidence analysis. IMT was associated with incidence of cognitive impairment after multiple adjustments (hazard ratio: 1.09, p=0.02 for each 0.1 mm increase in IMT). A total of 1311 participants with atherosclerosis data at baseline had the additional cognitive tests 10 years later. Larger IMT was associated with longer time to complete the Trail-Making Test-part B after multiple adjustments (0.1 mm IMT: 2.3 seconds longer, p=0.02). Plaque was not associated with incident cognitive impairment or cognitive test performance 10 years later. Conclusions In this population-based longitudinal study, carotid IMT was associated with a higher risk of developing cognitive impairment during the 10-year follow-up, and was associated with poorer performance in a test of executive function 10 years later. PMID:22854188

  14. LRP and PDGF signaling: a pathway to atherosclerosis.

    PubMed

    Boucher, Philippe; Gotthardt, Michael

    2004-02-01

    The low-density lipoprotein (LDL) receptor-related protein (LRP) is a member of the LDL receptor family. In addition to its role in endocytosis and uptake of multiple ligands, it is now apparent that LRP, like some other members of the family, is also involved in signal transduction. Through LRP, both endocytosis and signaling coexist at the surface of the plasma membrane and regulate critical cellular physiology and signal transduction events. This article focuses on the recently uncovered molecular mechanisms by which LRP, its ligand apolipoprotein E, and the platelet-derived growth factor receptor cooperate in the remodeling of the vascular wall and protect against atherosclerosis. PMID:15030790

  15. Fluorescent Molecular Tomography for In Vivo Imaging of Mouse Atherosclerosis.

    PubMed

    Arranz, Alicia; Rudin, Markus; Zaragoza, Carlos; Ripoll, Jorge

    2015-01-01

    Optical imaging technologies such as fluorescence molecular tomography (FMT) are gaining great relevance in cardiovascular research. The main reason is the increased number of available fluorescent agents, especially those termed "activatable probes," which remain quenched under baseline conditions and are fluorescent when a specific enzymatic activity is present. A major characteristic of FMT is the possibility of obtaining quantitative data of fluorescence signal distribution in a noninvasive fashion and using nonionizing radiation, making FMT an invaluable tool for longitudinal studies with biomedical applications. Here, we describe a standard procedure to perform FMT experiments in atherosclerosis mouse models, from the handling of the animals to the reconstruction of the 3D images. PMID:26445804

  16. Mechanistic similarities between trauma, atherosclerosis, and other inflammatory processes.

    PubMed

    Scalea, Joseph R; Bromberg, Jonathan; Bartlett, Stephen T; Scalea, Thomas M

    2015-12-01

    Most human diseases, including trauma, atherosclerosis, and malignancy, can be characterized by either an overexuberant inflammatory response or an inadequate immunologic response. As our understanding of the mechanisms underlying these inflammatory aberrations improves, so should our approach to the patient. The development of novel technologies capable of exploiting inflammatory mediators will undoubtedly play a role in future patient-directed therapies. Trauma surgeons are uniquely positioned to usher in a new era of patient diagnostics and patient-directed therapies based on an understanding of the immune system's response to stimuli. These improvements are likely to affect not only trauma care but all aspects of medicine. PMID:26304513

  17. FDG PET/CT Imaging of Carotid Atherosclerosis.

    PubMed

    Ali, Abdelrahman; Tawakol, Ahmed

    2016-02-01

    Atherosclerosis is a complex inflammatory process and an integral component of myocardial infarction and stroke. Atherosclerotic plaques can be detected using ultrasonography, myocardial perfusion imaging, coronary angiography, multidetector computed tomography (CT), and MR imaging. These modalities assess the luminal encroachment of the plaques or the structural features. Imaging plaque biology in concert with plaque structure may provide important insights. PET scanning using (18)F fluorodeoxyglucose. ((18)F FDG-PET) is commonly combined with CT scanning to characterize oncological processes. This review examines the role of (18)F FDG-PET/CT imaging in the characterization of atherosclerotic plaque biology. PMID:26610659

  18. Sexual dimorphism in rodent models of hypertension and atherosclerosis

    PubMed Central

    Bubb, Kristen J; Khambata, Rayomand S; Ahluwalia, Amrita

    2012-01-01

    Approximately one third of all deaths are attributed to cardiovascular disease (CVD), making it the biggest killer worldwide. Despite a number of therapeutic options available, the burden of CVD morbidity continues to grow indicating the need for continued research to address this unmet need. In this respect, investigation of the mechanisms underlying the protection that premenopausal females enjoy from cardiovascular-related disease and mortality is of interest. In this review, we discuss the essential role that rodent animal models play in enabling this field of research. In particular, we focus our discussion on models of hypertension and atherosclerosis. PMID:22582712

  19. Tissue Factor Pathway Inhibitor-2 Gene Polymorphisms Associate With Coronary Atherosclerosis in Chinese Population

    PubMed Central

    Yu, Jia; Liu, Rong-Le; Luo, Xin-Ping; Shi, Hai-ming; Ma, Duan; Pan, Jun-Jie; Ni, Huan-Chun

    2015-01-01

    Abstract Tissue factor pathway inhibitor-2 (TFPI-2) may play critical roles in the pathogenesis of atherosclerosis. In this study, we aimed to investigate the association between TFPI-2 gene polymorphisms and coronary atherosclerosis. Four hundred and seven patients with coronary atherosclerosis and 306 individuals with normal coronary artery were enrolled in the present study. Nine single-nucleotide polymorphisms (SNPs) (rs3763473, rs59805398, rs60215632, rs59999573, rs59740167, rs34489123, rs4517, rs4264, and rs4271) were detected with polymerase chain reaction-direct sequencing method. Severity of coronary atherosclerosis was assessed by Gensini score. After the baseline investigation, patients with coronary atherosclerosis were followed up for incidence of cardiovascular events (CVEs). Eight SNPs were in accordance with the Hardy–Weinberg equilibrium, and 8 haplotypes were constructed based on rs59999573, rs59740167, and rs34489123 after linkage disequilibrium and haplotype analysis. Two SNPs (rs59805398 and rs34489123) and 5 haplotypes correlated with coronary atherosclerosis even after adjustment by Gensini score. At follow-up (median 53 months, range 1–60 months), 85 patients experienced CVE. However, there was no strong association between the gene polymorphisms and the occurrence of CVE. Tissue factor pathway inhibitor-2 gene polymorphisms were associated with coronary atherosclerosis in the Chinese population, suggesting that the information about TFPI-2 gene polymorphisms was useful for assessing the risk of developing coronary atherosclerosis, but there was not enough evidence showing it could predict occurrence of CVE. PMID:26496276

  20. 76 FR 3146 - Submission for OMB Review; Comment Request; The Atherosclerosis Risk in Communities Study (ARIC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-19

    ... SERVICES National Institutes of Health Submission for OMB Review; Comment Request; The Atherosclerosis Risk... Atherosclerosis Risk in Communities Study (ARIC). Type of Information Collection Request: Revision of a currently... be used to further describe the risk factors, occurrence rates, and consequences of...

  1. 78 FR 77138 - Proposed Collection; 60-day Comment Request: The Atherosclerosis Risk in Communities Study (ARIC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-20

    ... Atherosclerosis Risk in Communities Study (ARIC) Summary: In compliance with the requirement of Section 3506(c) (2... Study (ARIC),--Revised, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health... primary objectives of the study are to: (1) investigate factors associated with both atherosclerosis...

  2. Prevention of Coronary Atherosclerosis: The Role of a College Health Service.

    ERIC Educational Resources Information Center

    Manchester, Ralph A.; Greenland, Philip

    1987-01-01

    This paper reviews the concept of behavioral risk factors for atherosclerosis which become entrenched in adolescence or young adulthood. Evidence favoring intervention in the adolescent years and a screening program at the University of Rochester Health Service are described. A preliminary strategy for prevention of atherosclerosis on campus is…

  3. 75 FR 7482 - Submission for OMB Review; Comment Request; The Atherosclerosis Risk in Communities Study (ARIC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-19

    ... From the Federal Register Online via the Government Printing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Submission for OMB Review; Comment Request; The Atherosclerosis Risk... Atherosclerosis Risk in Communities Study (ARIC). Type of Information Collection Request: Extension of a...

  4. Fire Suppression and Response

    NASA Technical Reports Server (NTRS)

    Ruff, Gary A.

    2004-01-01

    This report is concerned with the following topics regarding fire suppression:What is the relative effectiveness of candidate suppressants to extinguish a representative fire in reduced gravity, including high-O2 mole fraction, low -pressure environments? What are the relative advantages and disadvantages of physically acting and chemically-acting agents in spacecraft fire suppression? What are the O2 mole fraction and absolute pressure below which a fire cannot exist? What effect does gas-phase radiation play in the overall fire and post-fire environments? Are the candidate suppressants effective to extinguish fires on practical solid fuels? What is required to suppress non-flaming fires (smoldering and deep seated fires) in reduced gravity? How can idealized space experiment results be applied to a practical fire scenario? What is the optimal agent deployment strategy for space fire suppression?

  5. Abstract--Common carotid intima-media thickness (IMT) is a reliable measure of early atherosclerosis -its accurate

    E-print Network

    Whelan, Paul F.

    atherosclerosis - its accurate measurement can be used in the process of evaluating the presence and tracking vascular disease (gangrene) and kidney infarcts respectively. Early atherosclerosis (increased intima media diagnosis of atherosclerosis, prognosis prediction, and in the monitoring of responses to lifestyle

  6. Aortic smooth muscle cell proteoglycan synthesis in relation to atherosclerosis

    SciTech Connect

    Edwards, I.J.

    1989-01-01

    Proteoglycans (PG) are implicated in atherogenesis by their effects on tissue permeability and cell proliferation and their interaction with plasma low density lipoproteins. Using the pigeon model in which an atherosclerosis-susceptible (WC) and -resistant (SR) breed can be compared, PG synthesis by cultured aortic smooth muscle cells was examined by the use of ({sup 35}S)-sodium sulfate and ({sup 3}H)-serine or ({sup 3}H)-glucosamine as labeling precursors. In both SR and WC cells, the majority of newly synthesized PG were secreted into the media. Chondroitin sulfate (CS) PG and dermatan sulfate (DS) PG were the major PG produced. Total PG production was consistently lower in WC compared to SR cultures due in part to reduce PG synthesis but also to degradation of newly synthesized PG. Since increased DS-PG accompanines atherosclerosis progression, experiments were designed to test the hypothesis that macrophages modulate smooth muscle cell metabolism to cause increase DS-PG production. Cultured WC aortic smooth muscle cells were exposed to the media of cholesteryl ester-loaded pigeon peritoneal macrophages or a macrophage cell line P388D1 and the production of PG examined. Increasing concentration of conditioned media from both types of macrophages caused increased incorporation of {sup 35}S-sulfate into secreted PG, but no change in cell-associated PG. Lipopolysaccharide activation of P388D1 cells enhanced the effect.

  7. Wine, alcohol and atherosclerosis: clinical evidences and mechanisms.

    PubMed

    da Luz, P L; Coimbra, S R

    2004-09-01

    Atherosclerosis is a chronic inflammatory disease which may cause obstructions of the coronary, cerebral and peripheral arteries. It is typically multifactorial, most often dependent on risk factors such as hypercholesterolemia, diabetes, smoking, hypertension, sedentarism, and obesity. It is the single main cause of death in most developed countries due to myocardial infarction, angina, sudden death, and heart failure. Several epidemiological studies suggest that moderate alcohol intake, especially red wine, decrease cardiac mortality due to atherosclerosis. The alcohol effect is described by a J curve, suggesting that moderate drinkers may benefit while abstainers and heavy drinkers are at higher risk. Experimental studies indicate that most beneficial effects of drinking are attributable to flavonoids that are present in red wine, purple grape juice and several fruits and vegetables. The mechanisms include antiplatelet actions, increases in high-density lipoprotein, antioxidation, reduced endothelin-1 production, and increased endothelial nitric oxide synthase expression which causes augmented nitric oxide production by endothelial cells. These findings lead to the concept that moderate red wine drinking, in the absence of contraindications, may be beneficial to patients who are at risk of atherosclerotic cardiovascular events. Moreover, a diet based on fruits and vegetables containing flavonoids may be even more beneficial. PMID:15334193

  8. Macrophage Heterogeneity and Plasticity: Impact of Macrophage Biomarkers on Atherosclerosis

    PubMed Central

    Rojas, Joselyn; Salazar, Juan; Martínez, María Sofía; Palmar, Jim; Bautista, Jordan; Chávez-Castillo, Mervin; Gómez, Alexis; Bermúdez, Valmore

    2015-01-01

    Cardiovascular disease (CVD) is a global epidemic, currently representing the worldwide leading cause of morbidity and mortality. Atherosclerosis is the fundamental pathophysiologic component of CVD, where the immune system plays an essential role. Monocytes and macrophages are key mediators in this aspect: due to their heterogeneity and plasticity, these cells may act as either pro- or anti-inflammatory mediators. Indeed, monocytes may develop heterogeneous functional phenotypes depending on the predominating pro- or anti-inflammatory microenvironment within the lesion, resulting in classic, intermediate, and non-classic monocytes, each with strikingly differing features. Similarly, macrophages may also adopt heterogeneous profiles being mainly M1 and M2, the former showing a proinflammatory profile while the latter demonstrates anti-inflammatory traits; they are further subdivided in several subtypes with more specialized functions. Furthermore, macrophages may display plasticity by dynamically shifting between phenotypes in response to specific signals. Each of these distinct cell profiles is associated with diverse biomarkers which may be exploited for therapeutic intervention, including IL-10, IL-13, PPAR-?, LXR, NLRP3 inflammasomes, and microRNAs. Direct modulation of the molecular pathways concerning these potential macrophage-related targets represents a promising field for new therapeutic alternatives in atherosclerosis and CVD. PMID:26491604

  9. Conjugated linoleic acid modulation of risk factors associated with atherosclerosis

    PubMed Central

    Nakamura, Yukiko K; Flintoff-Dye, Nichole; Omaye, Stanley T

    2008-01-01

    Conjugated linoleic acid (CLA) has been the subject of extensive investigation regarding its possible benefits on a variety of human diseases. In some animal studies, CLA has been shown to have a beneficial effect on sclerotic lesions associated with atherosclerosis, be a possible anti-carcinogen, increase feed efficiency, and act as a lean body mass supplement. However, the results have been inconsistent, and the effects of CLA on atherogenesis appear to be dose-, isomer-, tissue-, and species-specific. Similarly, CLA trials in humans have resulted in conflicting findings. Both the human and animal study results may be attributed to contrasting doses of CLA, isomers, the coexistence of other dietary fatty acids, length of study, and inter-and/or intra-species diversities. Recent research advances have suggested the importance of CLA isomers in modulating gene expression involved in oxidative damage, fatty acid metabolism, immune/inflammatory responses, and ultimately atherosclerosis. Although the possible mechanisms of action of CLA have been suggested, they have yet to be determined. PMID:18718021

  10. Radionuclide imaging of experimental atherosclerosis with nonspecific polyclonal immunoglobulin G

    SciTech Connect

    Fischman, A.J.; Rubin, R.H.; Khaw, B.A.; Kramer, P.B.; Wilkinson, R.; Ahmad, M.; Needelman, M.; Locke, E.; Nossiff, N.D.; Strauss, H.W.

    1989-06-01

    The utility of nonspecific polyclonal IgG for external imaging of experimental atherosclerosis was tested in a series of rabbits after balloon catheter deendothelialization of the abdominal aorta. Following injection of /sup 111/In-IgG, /sup 111/In-Fc, or /sup 111/In-Fab serial images were recorded. In addition, several animals received /sup 125/I-low density lipoproteins (/sup 125/I-LDL), or /sup 125/I human serum albumin (/sup 125/I-HSA) as positive and negative controls. Forty-eight hours after injection of the radiolabeled proteins, the aortas were removed, divided into abdominal and thoracic regions, counted, and autoradiographed. The images acquired after injection of /sup 111/In-IgG and /sup 111/In-Fc, showed clear focal accumulation of radioactivity in the healing abdominal aorta. In contrast, the images obtained after injection of /sup 111/In-Fab did not show focal radionuclide accumulation. For /sup 111/In-IgG and /sup 111/In-Fc there were three to six times as many counts in the abdominal as in the thoracic aorta, while for /sup 111/In-Fab and /sup 125/I HSA, the abdominal and thoracic counts were nearly equal. The results suggest that radiolabeled IgG and Fc can be used to image experimental atherosclerosis.

  11. Atherosclerosis: Recent trials, new targets and future directions.

    PubMed

    Ladeiras-Lopes, Ricardo; Agewall, Stefan; Tawakol, Ahmed; Staels, Bart; Stein, Evan; Mentz, Robert J; Leite-Moreira, Adelino; Zannad, Faiez; Koenig, Wolfgang

    2015-08-01

    Mortality from cardiovascular diseases (CVD) represents the primary cause of death worldwide. Prevention or treatment of atherosclerosis and its clinical sequelae is a central goal in the management of patients with established vascular disease or those at high-risk for vascular events. This paper provides a review of the contemporary pharmacological armamentarium targeting atherosclerosis and also highlights strategies to support future clinical trial design. Powering future trials targeting LDL-cholesterol to its absolute reduction and including patients with a higher LDL-C despite optimal medical therapy (or unable to tolerate statins) will increase the odds of meaningful results. Mendelian randomization studies may identify new causal risk factors for CVD that would help in the selection of the patients most likely to benefit from a specific new compound. Furthermore, imaging techniques integrating a morphological and functional assessment such as IVUS, OCT, PET/CT and PET/MRI may represent in a near future robust "soft" endpoints to support successful translation of early research into meaningful phase III clinical outcome trials. PMID:26002254

  12. Hyperglycemia suppresses hepatic scavenger receptor class B type I expression.

    PubMed

    Murao, Koji; Yu, Xiao; Imachi, Hitomi; Cao, Wen M; Chen, Ke; Matsumoto, Kensuke; Nishiuchi, Takamasa; Wong, Norman C W; Ishida, Toshihiko

    2008-01-01

    Hyperglycemia is a major risk factor for atherosclerotic disease. Hepatic scavenger receptor class B type I (SR-BI) binds HDL particles that mediate reverse cholesterol transport and thus lowers the risk of atherosclerosis. Here we examined glucose regulation of SR-BI gene expression in both HepG2 cells and whole animals. Results showed that hepatic SR-BI mRNA, protein, and uptake of cholesterol from HDL were halved following 48 h of exposure to 22.4 vs. 5.6 mM glucose. As in the case of the cell culture model, hepatic expression of SR-BI was lower in diabetic rats than in euglycemic rats. Transcriptional activity of the human SR-BI promoter paralleled endogenous expression of the gene, and this activity was dependent upon the dose of glucose. Next, we used inhibitors of select signal transduction pathways to demonstrate that glucose suppression of SR-BI was sensitive to the p38 MAPK inhibitor. Expression of a constitutively active p38 MAPK inhibited SR-BI promoter activity in the presence or absence of glucose. A dominant-negative p38 MAPK abolished the inhibitory effect of glucose on promoter activity. Deletional analysis located a 50-bp fragment of the promoter that mediated the effects of glucose. Within this DNA fragment there were several specificity protein-1 (Sp1) binding sites, and cellular knockdown of Sp1 abrogated its suppression by glucose. Together, these results indicate that the glucose suppression of SR-B1 expression is partially mediated by the activation of the p38 MAPK-Sp1 pathway and raise the possibility that the inhibition of hepatic SR-BI expression under high-glucose conditions provides a mechanism for accelerated atherosclerosis in diabetics. PMID:17957039

  13. [CHRONIC FLUORIDE INTOXICATION AS A RISK FACTOR FOR THE DEVELOPMENT OF ATHEROSCLEROSIS].

    PubMed

    Korotenko, O Yu; Panev, N I; Zakharenkov, V V; Filimonov, S N; Semenova, E A; Panev, R N

    2015-01-01

    In workers employed in the aluminum industry, the main harmful production factor is exposure to fluoride salts, which can cause chronic fluoride intoxication. For the assessment of the impact of chronic fluoride intoxication on the development of atherosclerosis, we conducted a comprehensive survey of 87 aluminum-metal makers with chronic fluoride intoxication and 43 aluminum-metal makers without occupational diseases, mean age--52.1 ± 0.4 years. There were considered the presence and severity of atherosclerosis of brachiocephalic arteries, and the arteries of the lower extremities in the studied group, there was evaluated the effect of other risk factors for atherosclerosis (smoking, presence of hypertension, diabetes, dyslipidemia). With the use of Doppler ultrasound of the arteries it was revealed that in metallurgists with chronic fluoride intoxication atherosclerosis was detected in 73.6% versus 55.8% in persons of the comparison group. The performed analysis of the prevalence of main risk factors for atherosclerosis showed that in metal makers with chronic fluoride intoxication in combination with atherosclerosis hypertension is more common (in 54.7%) than in metallurgists with chronic fluoride intoxication without atherosclerosis--only 26.1%. According to the frequency of occurrence of smoking, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia, there were no significant differences between the metallurgists with chronic fluoride intoxication, with and without atherosclerosis, and the control group, the increase in LDL cholesterol occurs significantly more often in metal-makers with chronic fluoride intoxication in combination with atherosclerosis if compared to workers without occupational diseases. Thus, chronic fluoride intoxication acts as a risk factor in the development of atherosclerosis: atherosclerosis in metal-makers with chronic fluoride intoxication occurs more frequently than in workers who do not have professional pathology. Hypertension and elevated levels of LDL cholesterol were established to increase the relative risk of developing atherosclerosis in metallurgists with chronic fluoride intoxication. At that there are no significant differences in the prevalence of common risk factors for atherosclerosis (smoking, diabetes, hypercholesterolemia, hypertriglyceridemia). PMID:26625626

  14. Establishment and ultrasound characteristics of atherosclerosis in rhesus monkey

    PubMed Central

    2015-01-01

    Background Atherosclerosis is one of the main risk factors cause acute cerebral-cardio vascular diseases. It's of great significance to establish an atherosclerosis animal model that can mimic the characteristics and nature course of human patients. Therefore, a rhesus monkey model was induced by high-fat diet to monitor their lipid profile and intima-media thickness (IMT) of artery walls and study atherosclerosis progression. Methods Fifty male rhesus monkeys were enrolled in this study. All of these monkeys were aged 7 to 14 years with BMI >30 kg/m2. They were fed with high-fat diet containing 10% of fat for the first 48 weeks. Use ultrasound to measure the IMT at bilateral common carotid arteries and their bifurcations and aorta (AO) of the monkeys, and screen out the individuals with thickened IMT for the next phase. In the next 48 weeks, some of these monkeys (n = 4) were fed with standard diet containing 3% fat. Meanwhile the other monkeys (n = 5) were fed with high-fat diet for another 48 weeks. Their serum lipid level was monitored and arterial IMT was also determined periodically. Results Serum lipid level of all 50 monkeys elevated after fed with high-fat diet for the first 48 weeks. IMT thickening at right common carotid bifurcation and aorta (AO) was thickened in 9 monkeys. Furthermore, 4 of these 9 monkeys were fed with standard diet and other 5 monkeys were fed with high-fat diet in the following 48 weeks. The serum lipid level of the 4 monkeys recovered and their IMT at RBIF and AO did not progress. However, the lipid level of other 5 monkeys remained high, and their IMT thickening of AO progressed, and plaques and calcification focuses were found at the anterior wall of aorta near the bifurcation of common iliac artery. Conclusions After high-fat diet induction for 96 weeks, serum lipid levels of rhesus monkeys elevated significantly, which subsequently caused IMT thickening and plaques formation. When IMT thickening occurred, further vascular injury may be prevented by reducing diet fat content. Our study indicates that vascular injury of high-fat diet induced rhesus monkey is similar to that of human in position and progression. PMID:25602196

  15. Prospects for prevention of atherosclerosis in the young.

    PubMed

    Kannel, W B

    1976-10-01

    There appears to be a need to protect our young from an atherogenic way of life. The average male child today has one chance in three of a cardiovascular catastrophe before age 60. Atherosclerosis and the conditions which predispose appear to have their onset in childhood. Correctable precursors of cardiovascular disease have been identified, and their contribution to risk has been estimated not only for adults but for college students as well. An analysis of the combined impact of atherogenic risk factors indicates that they exert greater force early in life than later. Although the optimal time to begin prophylaxis is not established, there is evidence to suggest that measures instituted late in life when lesions are advanced is of only limited value. Prevention of atherosclerosis is best viewed as a family affair since the propensity to disease and contributing factors tend to be shared by family members. It is also difficult to implement effectively preventive measures which include dietary changes, weight control, exercise and restriction of cigarettes for one family member without involving the rest of the family. Optimal levels of the correctable precursors of cardiovascular disease are not established for children. However, the rise in serum lipids, blood pressure, weight and blood sugar observed in transition from childhood to adult life is not inevitable, or desirable. Paediatricians can alter the appalling cardiovascular mortality statistics by not allowing the process or the habits and conditions which promote it to reach an irreversible stage. Cardiovascular disease may well begin in childhood with "medical trivia" such as a tendency to obesity, moderate cholesterol and blood pressure elevations, lack of exercise and the cigarette habit. In some respects a heart attack at age 45 can be regarded as a failure of the paediatrician. Awaiting proof of the efficacy of the indicated prophylactic measures is not acceptable since this will be a long time in coming. We must learn how to correct risk factors effectively in childhood as soon as they appear. We must establish goals based on optimal as distinct from usual levels of risk factors. Paediatricians' resolve about prevention of atherosclerosis in childhood needs to be strengthened and we must develop a sense of urgency about this. PMID:1071869

  16. Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

    SciTech Connect

    Son, Dong Ju; Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA ; Kim, Soo Yeon; Han, Seong Su; Kim, Chan Woo; Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA; Department of Bioinspired Science, Ehwa Womans University, Seoul ; Kumar, Sandeep; Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA ; Park, Byeoung Soo; Lee, Sung Eun; Yun, Yeo Pyo; Jo, Hanjoong; Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA; Department of Bioinspired Science, Ehwa Womans University, Seoul ; Park, Young Hyun

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.

  17. Prenatal Arsenic Exposure Alters Gene Expression in the Adult Liver to a Proinflammatory State Contributing to Accelerated Atherosclerosis

    PubMed Central

    States, J. Christopher; Singh, Amar V.; Knudsen, Thomas B.; Rouchka, Eric C.; Ngalame, Ntube O.; Arteel, Gavin E.; Piao, Yulan; Ko, Minoru S. H.

    2012-01-01

    The mechanisms by which environmental toxicants alter developmental processes predisposing individuals to adult onset chronic disease are not well-understood. Transplacental arsenic exposure promotes atherogenesis in apolipoprotein E-knockout (ApoE?/?) mice. Because the liver plays a central role in atherosclerosis, diabetes and metabolic syndrome, we hypothesized that accelerated atherosclerosis may be linked to altered hepatic development. This hypothesis was tested in ApoE?/? mice exposed to 49 ppm arsenic in utero from gestational day (GD) 8 to term. GD18 hepatic arsenic was 1.2 µg/g in dams and 350 ng/g in fetuses. The hepatic transcriptome was evaluated by microarray analysis to assess mRNA and microRNA abundance in control and exposed pups at postnatal day (PND) 1 and PND70. Arsenic exposure altered postnatal developmental trajectory of mRNA and microRNA profiles. We identified an arsenic exposure related 51-gene signature at PND1 and PND70 with several hubs of interaction (Hspa8, IgM and Hnf4a). Gene ontology (GO) annotation analyses indicated that pathways for gluconeogenesis and glycolysis were suppressed in exposed pups at PND1, and pathways for protein export, ribosome, antigen processing and presentation, and complement and coagulation cascades were induced by PND70. Promoter analysis of differentially-expressed transcripts identified enriched transcription factor binding sites and clustering to common regulatory sites. SREBP1 binding sites were identified in about 16% of PND70 differentially-expressed genes. Western blot analysis confirmed changes in the liver at PND70 that included increases of heat shock protein 70 (Hspa8) and active SREBP1. Plasma AST and ALT levels were increased at PND70. These results suggest that transplacental arsenic exposure alters developmental programming in fetal liver, leading to an enduring stress and proinflammatory response postnatally that may contribute to early onset of atherosclerosis. Genes containing SREBP1 binding sites also suggest pathways for diabetes mellitus and rheumatoid arthritis, both diseases that contribute to increased cardiovascular disease in humans. PMID:22719926

  18. Soluble epoxide hydrolase is involved in the development of atherosclerosis and arterial neointima formation by regulating smooth muscle cell migration.

    PubMed

    Wang, Qingjie; Huo, Leijun; He, Jinlong; Ding, Wenshuang; Su, Hang; Tian, Dongping; Welch, Carrie; Hammock, Bruce D; Ai, Ding; Zhu, Yi

    2015-12-01

    Epoxyeicosatrienoic acids (EETs) have beneficial effects on cardiovascular disease. Soluble epoxide hydrolase (sEH) metabolizes EETs to less active diols, thus diminishing their biological activity. sEH inhibitors can suppress the progression of atherosclerotic lesions in animal models. However, the regulation of sEH in vascular smooth muscle cells (VSMCs) and role of sEH in patients with atherosclerosis have not been evaluated. We hypothesize that sEH in VSMCs plays a pivotal role in atherosclerosis and injury-induced neointima formation. In this study, sEH expression in human autopsy atherosclerotic plaque was determined by immunohistochemistry. In cultured rat and human VSMCs, the phenotypic switching marker and sEH expression induced by platelet-derived growth factor-BB (PDGF-BB) were examined by Western blot analysis. Carotid-artery balloon injury was performed after adenovirus-mediated overexpression of sEH or oral administration of a potent sEH inhibitor in Sprague-Dawley rats. sEH was highly expressed in VSMCs of the intima and media within human atherosclerotic plaque. In vitro, PDGF-BB upregulated the expression in VSMCs after transcription and promoted cell proliferation and migration; the latter effect could be largely attenuated by an sEH inhibitor. Adenovirus-mediated overexpression of sEH could mimic the effect of PDGF-BB and induce VSMC proliferation and migration. In vivo, the sEH inhibitor led to a significant decrease in injury-induced neointima formation in a rat carotid-artery injury model. These data establish the effect of sEH expression on atherosclerotic progression and vascular remodeling after injury, thus identifying a novel integrative role for sEH in VSMC phenotypic modulation and migration. Blocking sEH activity may be a potential therapeutic approach for ameliorating vascular occlusive disease. PMID:26453326

  19. Atherosclerosis in psoriatic disease: latest evidence and clinical implications

    PubMed Central

    Eder, Lihi; Gladman, Dafna D.

    2015-01-01

    It is widely accepted that atherosclerosis is caused by chronic low-grade inflammation that results from an interaction between immune mechanisms and metabolic abnormalities within the vessel wall. Population-based studies have found an increased cardiovascular risk in patients with psoriasis and psoriatic arthritis (PsA). This risk is higher in patients with severe disease phenotypes, such as those with severe psoriasis and with musculoskeletal inflammation. Higher levels of inflammatory biomarkers also predict the development of clinical cardiovascular events in these patients. The effect of medications used for PsA on cardiovascular risk is limited to observational studies. Antitumor necrosis factor agents and methotrexate have been associated with reduced cardiovascular risk. These data highlight the importance of screening for cardiovascular risk factors in these patients. PMID:26425147

  20. Peculiarities of spectroscopic information of whole blood in atherosclerosis

    NASA Astrophysics Data System (ADS)

    Khairullina, Alphiya Y.; Oleinik, Tatiana V.; Yusupova, Lira B.; Prigoun, Natalia

    1995-01-01

    The coefficient of diffuse reflection and light transmission measurements in an optically thick layer of blood at atherosclerosis conditions under multiple scattering of light in the visual and nearest IR-spectra region (590 -900 nm) were measured for calculation of the absorption coefficients of the material of particles and surrounding medium K((lambda) ) and parameter Q (the latter parameter was defined by the sizes of erythrocytes and aggregates and by refraction coefficient of red cells relative to plasma at atherosclerosis). For the main quantitative spectroscopy of particles the K1((lambda) ) for known value of K((lambda) ) and the parameter Q determinations it is necessary to have the knowledge of relative volume part H occupied by particles. In the case of a high concentration of particles H >= 0.2 as it takes place in the blood the parameters Q and K((lambda) ) are in dependence of H (H - is hematocrit ration for the case of whole blood). It should be noted that spectroscopy of multiple scattering light can give some information out of main absorption bands with the higher accuracy and higher light scattering. The latter value provides the opportunity of determination of faint absorption bands which couldn't be achieved by other methods. The method proposed is characterized by absence of probe preparations, approach to in viva conditions, expressivity, and high informativity of each experiment. A many-fold investigation of the blood of healthy men in the spectral region 650 - 810 nm shows the electron spectrum of absorption of molecular hemoglobin hem is the most optically active blood spectra component K((lambda) ). The broadening of spectral investigations, as in short wave or long wave areas of the spectrum, by the use of multiple scattering methods for calculations of K((lambda) ) and Q((lambda) ) enlarges the number of chromophores studied.

  1. Vascular fluid mechanics, the arterial wall, and atherosclerosis.

    PubMed

    Nerem, R M

    1992-08-01

    Atherosclerosis, a disease of large- and medium-size arteries, is the chief cause of death in the United States and in most of the western world. Severe atherosclerosis interferes with blood flow; however, even in the early stages of the disease, i.e. during atherogenesis, there is believed to be an important relationship between the disease processes and the characteristics of the blood flow in the arteries. Atherogenesis involves complex cascades of interactions among many factors. Included in this are fluid mechanical factors which are believed to be a cause of the highly focal nature of the disease. From in vivo studies, there is evidence of hemodynamic influences on the endothelium, on intimal thickening, and on monocyte recruitment. In addition, cell culture studies have demonstrated the important effect of a cell's mechanical environment on structure and function. Most of this evidence is for the endothelial cell, which is believed to be a key mediator of any hemodynamic effect, and it is now well documented that cultured endothelial monolayers, in response to a fluid flow-imposed laminar shear stress, undergo a variety of changes in structure and function. In spite of the progress in recent years, there are many areas in which further work will provide important new information. One of these is in the engineering of the cell culture environment so as to make it more physiologic. Animal studies also are essential in our efforts to understand atherogenesis, and it is clear that we need better information on the pattern of the disease and its temporal development in humans and animal models, as well as the specific underlying biologic events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1522720

  2. Pattern recognition of magnetic resonance images with application to atherosclerosis

    SciTech Connect

    Carman, C.S.

    1989-01-01

    Magnetic resonance imaging provides excellent soft tissue contrast enabling the non-invasive visualization of soft tissue diseases. The quantification of tissues visible in MR images would significantly increase the diagnostic information available. While tissue selection methods exist for CT images, those same methods do not work with MR images. This dissertation focuses on the application of image processing and pattern recognition techniques to MR images for the identification and quantification of soft tissues, atherosclerosis in particular. Atherosclerosis is a chronic disease of human arteries responsible for significant mortality and medical expense. Current diagnostic methods are invasive and carry significant risk. Supervised pattern recognition methods were investigated for tissue identification in MR images. The classifiers were trained A Fisher linear classifier successfully identified the tissues of interest from MR images of excised arteries, performing better than a minimum distance to the means classifier. Quantitative measures of the disease state were computed from the results and 3-D displays were generated of the diseased anatomy. For tissue in vivo, adequate histology can be difficult to collect, increasing the difficulty of training the classifiers and making the results less accurate. Cluster analysis was used in this dissertation to generate the training information. A new cluster analysis method was developed. ISODATA was modified to use hierarchical stopping rules. The new method was tested in a Monte Carlo study and with real world data sets. Comparisons were made with published methods using the same data. An information theoretic criterion, the CAIC, was found to be an excellent criteria for hierarchical stopping rules.

  3. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    SciTech Connect

    Hsieh, Yi-Chen; Lien, Li-Ming; School of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan ; Chung, Wen-Ting; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan ; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan ; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields} A case-control study was conducted to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. {yields} Arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate atherosclerosis risk in individuals with high levels of arsenic in well water.

  4. MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis.

    PubMed

    Ouimet, Mireille; Ediriweera, Hasini N; Gundra, U Mahesh; Sheedy, Frederick J; Ramkhelawon, Bhama; Hutchison, Susan B; Rinehold, Kaitlyn; van Solingen, Coen; Fullerton, Morgan D; Cecchini, Katharine; Rayner, Katey J; Steinberg, Gregory R; Zamore, Phillip D; Fisher, Edward A; Loke, P'ng; Moore, Kathryn J

    2015-01-01

    Cellular metabolism is increasingly recognized as a controller of immune cell fate and function. MicroRNA-33 (miR-33) regulates cellular lipid metabolism and represses genes involved in cholesterol efflux, HDL biogenesis, and fatty acid oxidation. Here, we determined that miR-33-mediated disruption of the balance of aerobic glycolysis and mitochondrial oxidative phosphorylation instructs macrophage inflammatory polarization and shapes innate and adaptive immune responses. Macrophage-specific Mir33 deletion increased oxidative respiration, enhanced spare respiratory capacity, and induced an M2 macrophage polarization-associated gene profile. Furthermore, miR-33-mediated M2 polarization required miR-33 targeting of the energy sensor AMP-activated protein kinase (AMPK), but not cholesterol efflux. Notably, miR-33 inhibition increased macrophage expression of the retinoic acid-producing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1A2) and retinal dehydrogenase activity both in vitro and in a mouse model. Consistent with the ability of retinoic acid to foster inducible Tregs, miR-33-depleted macrophages had an enhanced capacity to induce forkhead box P3 (FOXP3) expression in naive CD4+ T cells. Finally, treatment of hypercholesterolemic mice with miR-33 inhibitors for 8 weeks resulted in accumulation of inflammation-suppressing M2 macrophages and FOXP3+ Tregs in plaques and reduced atherosclerosis progression. Collectively, these results reveal that miR-33 regulates macrophage inflammation and demonstrate that miR-33 antagonism is atheroprotective, in part, by reducing plaque inflammation by promoting M2 macrophage polarization and Treg induction. PMID:26517695

  5. Growth hormone suppression test

    MedlinePLUS

    GH suppression test; Glucose loading test ... right away. The lab measures the glucose and GH levels in each sample. ... is because exercise or increased activity can change GH levels. If your child is to have this ...

  6. Association of SERPINA9 gene variants with carotid artery atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study

    PubMed Central

    Tang, Weihong; Morrison, Alanna; Wasserman, Bruce A; Folsom, Aaron R; Sun, Wei; Campbell, Stephen; Kao, W H Linda; Boerwinkle, Eric

    2013-01-01

    The SNP rs11628722 in the SERPINA9 gene was previously associated with incident ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. Centerin, the protein encoded by SERPINA9, is involved in maturation and maintenance of naïve B cells, which play a role in atherogenesis. We investigated whether 21 tag SNPs in the SERPINA9 gene are associated with features of carotid artery atherosclerotic plaque measured by magnetic resonance imaging (MRI). Carotid MRI data were obtained from 1,282 European Americans and 341 African Americans of the ARIC Carotid MRI study, which recruited participants from ARIC by a stratified sampling plan that over-sampled participants with carotid intima-media thickening. Five MRI measures, focused on carotid wall volume, wall thickness, and lipid core, were analyzed. Genetic associations between the MRI measurements and each of the 21 SNPs were analyzed in linear regression models with adjustment for sample weights and traditional risk factors. Rs11628722 was tested a priori. In African Americans, rs11628722 was significantly associated with carotid wall volume (p < 0.05). Among the other 20 SNPs, adjusted for multiple testing, rs4905204, which encodes an Ala to Val amino acid change, was significantly associated with maximum wall thickness (p < 0.000625) and suggestively associated with total wall volume (p < 0.0026) in European Americans. In conclusion, SNPs in the SERPINA9 gene showed race-specific associations with characteristics of carotid atherosclerotic plaques. Replications in other populations are needed to validate findings of this study and to establish the SERPINA9 gene as a candidate in the etiology of carotid atherosclerosis. PMID:24319541

  7. Bio390 Atherosclerosis and Resistance thanks to Dr. J.F. Anderson,

    E-print Network

    Prestwich, Ken

    is required. A consequence of atherosclerosis is elevated blood pressure. High. If the flow of blood is to continue at its usual rate, a higher pressure blood pressure, in turn, has many undesirable effects, one of them being

  8. Inflammatory therapeutic targets in coronary atherosclerosis—from molecular biology to clinical application

    PubMed Central

    Linden, Fabian; Domschke, Gabriele; Erbel, Christian; Akhavanpoor, Mohammadreza; Katus, Hugo A.; Gleissner, Christian A.

    2014-01-01

    Atherosclerosis is the leading cause of death worldwide. Over the past two decades, it has been clearly recognized that atherosclerosis is an inflammatory disease of the arterial wall. Accumulating data from animal experiments have supported this hypothesis, however, clinical applications making use of this knowledge remain scarce. In spite of optimal interventional and medical therapy, the risk for recurrent myocardial infarction remains by about 20% over 3 years after acute coronary syndromes, novel therapies to prevent atherogenesis or treat atherosclerosis are urgently needed. This review summarizes selected potential molecular inflammatory targets that may be of clinical relevance. We also review recent and ongoing clinical trails that target inflammatory processes aiming at preventing adverse cardiovascular events. Overall, it seems surprising that translation of basic science into clinical practice has not been a great success. In conclusion, we propose to focus on specific efforts that promote translational science in order to improve outcome and prognosis of patients suffering from atherosclerosis. PMID:25484870

  9. Regulation of the renin–angiotensin system in coronary atherosclerosis: A review of the literature

    PubMed Central

    Hammoud, Ramadan A; Vaccari, Christopher S; Nagamia, Sameer H; Khan, Bobby V

    2007-01-01

    Activation of the renin–angiotensin system (RAS) is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. There is strong evidence that the RAS has effects on the mechanisms of action of atherosclerosis, including fibrinolytic balance, endothelial function, and plaque stability. Pharmacological inhibition of the renin angiotensin system includes angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and renin inhibitors. These agents have clinical benefits in reducing morbidity and mortality in the management of hypertension. In addition, ACE inhibitors and ARBs have shown to be effective in the management of congestive heart failure and acute myocardial infarction. This review article discusses the biochemical and molecular mechanisms involving the RAS in coronary atherosclerosis as well as the effects of RAS inhibition in clinical studies involving coronary atherosclerosis. PMID:18200812

  10. Thermal-based probe for testing endothelial dysfunction and possible implications for diagnosing atherosclerosis

    E-print Network

    Lediju, Muyinatu A. (Muyinatu Adebisi)

    2006-01-01

    Endothelial dysfunction is a precursor to atherosclerosis. Thus, the vascular health of an individual can be assessed if endothelial dysfunction can be readily and unambiguously quantified. A thermal-based approach using ...

  11. Stress-induced cardiac autonomic reactivity and preclinical atherosclerosis: does arterial elasticity modify the association?

    PubMed

    Chumaeva, Nadja; Hintsanen, Mirka; Pulkki-Råback, Laura; Merjonen, Päivi; Elovainio, Marko; Hintsa, Taina; Juonala, Markus; Kähönen, Mika; Raitakari, Olli T; Keltikangas-Järvinen, Liisa

    2015-11-01

    The effect of acute mental stress on atherosclerosis can be estimated using arterial elasticity measured by carotid artery distensibility (Cdist). We examined the interactive effect of acute stress-induced cardiac reactivity and Cdist to preclinical atherosclerosis assessed by carotid intima-media thickness (IMT) in 58 healthy adults aged 24-39 years participated in the epidemiological Young Finns Study. Cdist and IMT were measured ultrasonographically. Impedance electrocardiography was used to measure acute mental stress-induced cardiac autonomic responses: heart rate (HR), respiratory sinus arrhythmia and pre-ejection period after the mental arithmetic and the public speaking tasks. Interactions between HR reactivity and Cdist in relation to preclinical atherosclerosis were found. The results imply that elevated HR reactivity to acute mental stress is related to less atherosclerosis among healthy participants with higher arterial elasticity. Possibly, increased cardiac reactivity in response to challenging tasks is an adaptive reaction related to better cardiovascular health. PMID:26365028

  12. Mutation in KERA Identified by Linkage Analysis and Targeted Resequencing in a Pedigree with Premature Atherosclerosis

    PubMed Central

    van Capelleveen, Julian C.; Bot, Ilze; de Jager, Saskia C.; van Eck, Miranda; Jolley, Jennifer; Kuiper, Johan; Stephens, Jonathon; Albers, Cornelius A.; Vosmeer, C. Ruben; Kruize, Heleen; Geerke, Daan P.; van der Wal, Allard C.; van der Loos, Chris M.; Kastelein, John J. P.; Trip, Mieke D.

    2014-01-01

    Aims Genetic factors explain a proportion of the inter-individual variation in the risk for atherosclerotic events, but the genetic basis of atherosclerosis and atherothrombosis in families with Mendelian forms of premature atherosclerosis is incompletely understood. We set out to unravel the molecular pathology in a large kindred with an autosomal dominant inherited form of premature atherosclerosis. Methods and Results Parametric linkage analysis was performed in a pedigree comprising 4 generations, of which a total of 11 members suffered from premature vascular events. A parametric LOD-score of 3.31 was observed for a 4.4 Mb interval on chromosome 12. Upon sequencing, a non-synonymous variant in KERA (c.920C>G; p.Ser307Cys) was identified. The variant was absent from nearly 28,000 individuals, including 2,571 patients with premature atherosclerosis. KERA, a proteoglycan protein, was expressed in lipid-rich areas of human atherosclerotic lesions, but not in healthy arterial specimens. Moreover, KERA expression in plaques was significantly associated with plaque size in a carotid-collar Apoe?/? mice (r2?=?0.69; p<0.0001). Conclusion A rare variant in KERA was identified in a large kindred with premature atherosclerosis. The identification of KERA in atherosclerotic plaque specimen in humans and mice lends support to its potential role in atherosclerosis. PMID:24879339

  13. Explosion suppression system

    DOEpatents

    Sapko, Michael J. (Finleyville, PA); Cortese, Robert A. (Pittsburgh, PA)

    1992-01-01

    An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

  14. Vascular expression of extracellular superoxide dismutase in atherosclerosis.

    PubMed Central

    Fukai, T; Galis, Z S; Meng, X P; Parthasarathy, S; Harrison, D G

    1998-01-01

    We characterized a novel form of extracellular superoxide dismutase (ecSOD) in atherosclerotic vessels. Specific activity and protein expression of ecSOD was increased two- to threefold in apo E-deficient compared with control aortas. RNase protection assays demonstrated that the expected ecSOD transcript was not increased in either apo E-deficient mice or cholesterol-fed LDL receptor-deficient mice, but that a second, lower molecular weight transcript was present and became predominant as atherosclerosis progressed. Sequence analysis revealed that this novel ecSOD has a 10-bp deletion in the 3' untranslated region and an asparagine to aspartic acid mutation at amino acid 21. Studies of isolated macrophages and immunohistochemistry suggested that the truncated ecSOD transcript was expressed by lipid-laden but not control macrophages. Recombinant wild-type and novel ecSODs expressed in Sf9 cells exhibited similar SOD activities. These experiments show that ecSOD expression is increased in atherosclerotic vessels and that this is characterized by an alteration in mRNA and protein structure. Further, the source of this altered ecSOD is likely the lipid-laden macrophage. The enzymatic properties of this novel ecSOD may have important implications for the function of the lipid-laden macrophage and the atherosclerotic process. PMID:9593766

  15. Potential contributions of intimal and plaque hypoxia to atherosclerosis.

    PubMed

    Fong, Guo-Hua

    2015-06-01

    Injury of arterial endothelium by abnormal shear stress and other insults induces migration and proliferation of vascular smooth muscle cells (VSMCs), which in turn leads to intimal thickening, hypoxia, and vasa vasorum angiogenesis. The resultant new blood vessels extend from the tunica media into the outer intima, allowing blood-borne oxidized low-density lipoprotein (oxLDL) particles to accumulate in outer intimal tissues by extravasation through local capillaries. In response to oxLDL accumulation, monocytes infiltrate into arterial wall tissues, where they differentiate into macrophages and subsequently evolve into foam cells by uptaking large quantities of oxLDL particles, the latter process being stimulated by hypoxia. Increased oxygen demand due to expanding macrophage and foam cell populations contributes to persistent hypoxia in plaque lesions, whereas hypoxia further promotes plaque growth by stimulating angiogenesis, monocyte infiltration, and oxLDL uptake into macrophages. Molecularly, the accumulation of hypoxia-inducible factor (HIF)-1? and the expression of its target genes mediate many of the hypoxia-induced processes during plaque initiation and growth. It is hoped that further understanding of the underlying mechanisms may lead to novel therapies for effective intervention of atherosclerosis. PMID:25876920

  16. Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia

    PubMed Central

    Roher, Alex E.; Tyas, Suzanne L.; Maarouf, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Emmerling, Mark R.; Garami, Zsolt; Belohlavek, Marek; Sabbagh, Marwan N.; Sue, Lucia I.; Beach, Thomas G.

    2010-01-01

    Background A substantial body of evidence amassed from epidemiologic, correlative and experimental studies strongly associates atherosclerotic vascular disease (AVD) with Alzheimer's disease (AD). Depending on the precise interrelationship between AVD and AD, systematic application of interventions to maintain vascular health and function as a component of standard AD therapy offers the prospect of mitigating what is presently the inexorable course of dementia. To assess this hypothesis it is vital to rigorously establish the measures of AVD that are most strongly associated with an AD diagnosis. Methods A precise neuropathological diagnosis was established for all subjects using a battery of genetic, clinical, and histological methods. The severity of atherosclerosis in the circle of Willis (CW) was quantified by direct digitized measurement of arterial occlusion in postmortem specimens and compared between AD and non-demented control (NDC) groups by calculating a corresponding index of occlusion. Results Atherosclerotic occlusion of the CW arteries was more extensive in the AD group than the NDC group. Statistically significant differences were also observed between control and AD groups with regard to Braak stage, total plaque score, total NFT score, total white matter rarefaction score, brain weight, MMSE scores and apolipoprotein E allelic frequencies. Conclusions Our results, combined with a consideration of the multifaceted impacts of impaired cerebral circulation, suggest an immediate need for prospective clinical trials to assess the efficacy of AD prevention using anti-atherosclerotic agents. PMID:21388893

  17. STAT4 contributes to adipose tissue inflammation and atherosclerosis.

    PubMed

    Dobrian, A D; Hatcher, M A; Brotman, J J; Galkina, E V; Taghavie-Moghadam, P; Pei, H; Haynes, B A; Nadler, J L

    2015-10-01

    Adipose tissue (AT) inflammation is an emerging factor contributing to cardiovascular disease. STAT4 is a transcription factor expressed in adipocytes and in immune cells and contributes to AT inflammation and insulin resistance in obesity. The objective of this study was to determine the effect of STAT4 deficiency on visceral and peri-aortic AT inflammation in a model of atherosclerosis without obesity. Stat4(-/-)Apoe(-/-) mice and Apoe(-/-) controls were kept either on chow or Western diet for 12 weeks. Visceral and peri-aortic AT were collected and analyzed for immune composition by flow cytometry and for cytokine/chemokine expression by real-time PCR. Stat4(-/-)Apoe(-/-) and Apoe(-/-) mice had similar body weight, plasma glucose, and lipids. Western diet significantly increased macrophage, CD4+, CD8+, and NK cells in peri-aortic and visceral fat in Apoe(-/-) mice. In contrast, in Stat4(-/-)Apoe(-/-) mice, a Western diet failed to increase the percentage of immune cells infiltrating the AT. Also, IL12p40, TNFa, CCL5, CXCL10, and CX3CL1 were significantly reduced in the peri-aortic fat in Stat4(-/-)Apoe(-/-) mice. Importantly, Stat4(-/-)Apoe(-/-) mice on a Western diet had significantly reduced plaque burden vs Apoe(-/-) controls. In conclusion, STAT4 deletion reduces inflammation in peri-vascular and visceral AT and this may contribute via direct or indirect effects to reduced atheroma formation. PMID:26285907

  18. Occupational stress and subclinical atherosclerosis: a systematic review

    PubMed Central

    Wilson, Mark D; Conroy, Lorraine M; Dorevitch, Samuel

    2014-01-01

    Background: Stress is a common hazard in the work environment and is associated with multiple adverse health effects. The association between work-related stress (WRS) and cardiovascular disease has been established in a number of epidemiological studies. Methods: A systematic review was conducted according to the PRISMA statement of the English literature involving WRS and carotid artery intima media thickness (CIMT). Results: Four cohorts and six cross-sectional studies of occupational stress and CIMT were identified. All cohorts and five of the cross-sectional studies reported a significant positive association, while one reported an inverse association of WRS and CIMT. Discussion: The weight of the evidence that we were able to identify suggests that occupational stress results in an increased risk of atherosclerosis, assessed via CIMT. Studies that include longitudinal measures of stress and intermediate cardiac endpoints, with adequate accounting for confounders, are needed. Interventional studies should also be conducted to determine whether CIMT progression can be prevented with workplace stress reduction. PMID:25072637

  19. The Interaction Between IGF-1, Atherosclerosis and Vascular Aging

    PubMed Central

    Higashi, Yusuke; Quevedo, Henry C.; Tiwari, Summit; Sukhanov, Sergiy; Shai, Shaw-Yung; Anwar, Asif; Delafontaine, Patrice

    2014-01-01

    The process of vascular aging encompasses alterations in the function of endothelial (EC) and vascular smooth muscle cells (VSMCs) via oxidation, inflammation, cell senescence and epigenetic modifications, increasing the probability of atherosclerosis. Aged vessels exhibit decreased endothelial antithrombogenic properties, increased reactive oxygen species (ROS) generation and inflammatory signaling, increased migration of VSMCs to the subintimal space, impaired angiogenesis and increased elastin degradation. The key initiating step in atherogenesis is subendothelial accumulation of apolipoprotein-B containing low density lipoproteins resulting in activation of endothelial cells and recruitment of monocytes. Activated endothelial cells secrete “chemokines” that interact with cognate chemokine receptors on monocytes and promote directional migration. Recruitment of immune cells establishes a pro-inflammatory status, further causing elevated oxidative stress, which in turn triggers a series of events including apoptotic or necrotic death of vascular and non-vascular cells. Increased oxidative stress is also considered to be a key factor in mechanisms of aging-associated changes in tissue integrity and function. Experimental evidence indicates that insulin-like growth factor-1 (IGF-1) exerts anti-oxidant, anti-inflammatory and pro-survival effects on the vasculature, reducing atherosclerotic plaque burden and promoting features of atherosclerotic plaque stability. PMID:24943302

  20. Vascular health late after Kawasaki disease: implications for accelerated atherosclerosis

    PubMed Central

    2014-01-01

    Kawasaki disease (KD), an acute vasculitis that primarily affects young children, is the most common acquired paediatric cardiovascular disease in developed countries. While sequelae of arterial inflammation in the acute phase of KD are well documented, its late effects on vascular health are increasingly unveiled. Late vascular dysfunction is characterized by structural alterations and functional impairment in term of arterial stiffening and endothelial dysfunction and shown to involve both coronary and systemic arteries. Further evidence suggests that continuous low grade inflammation and ongoing active remodeling of coronary arterial lesions occur late after acute illness and may play a role in structural and functional alterations of the arteries. Potential importance of genetic modulation on vascular health late after KD is implicated by associations between mannose binding lectin and inflammatory gene polymorphisms with severity of peripheral arterial stiffening and carotid intima-media thickening. The changes in cholesterol and lipoproteins levels late after KD further appear similar to those proposed to be atherogenic. While data on adverse vascular health are less controversial in patients with persistent or regressed coronary arterial aneurysms, data appear conflicting in individuals with no coronary arterial involvements or only transient coronary ectasia. Notwithstanding, concerns have been raised with regard to predisposition of KD in childhood to accelerated atherosclerosis in adulthood. Until further evidence-based data are available, however, it remains important to assess and monitor cardiovascular risk factors and to promote cardiovascular health in children with a history of KD in the long term. PMID:25550701

  1. Impact of Hydroxychloroquine on Atherosclerosis and Vascular Stiffness in the Presence of Chronic Kidney Disease

    PubMed Central

    Shukla, Ashutosh M.; Bose, Chhanda; Karaduta, Oleg K.; Apostolov, Eugene O.; Kaushal, Gur P.; Fahmi, Tariq; Segal, Mark S.; Shah, Sudhir V.

    2015-01-01

    Cardiovascular disease is the largest cause of morbidity and mortality among patients with chronic kidney disease (CKD) and end-stage kidney disease, with nearly half of all deaths attributed to cardiovascular disease. Hydroxychloroquine (HCQ), an anti-inflammatory drug, has been shown to have multiple pleiotropic actions relevant to atherosclerosis. We conducted a proof-of-efficacy study to evaluate the effects of hydroxychloroquine in an animal model of atherosclerosis in ApoE knockout mice with and without chronic kidney disease. Forty male, 6-week-old mice were divided into four groups in a 2 x 2 design: sham placebo group; sham treatment group; CKD placebo group; and CKD treatment group. CKD was induced by a two-step surgical procedure. All mice received a high-fat diet through the study duration and were sacrificed after 16 weeks of therapy. Mice were monitored with ante-mortem ultrasonic echography (AUE) for atherosclerosis and vascular stiffness and with post-mortem histology studies for atherosclerosis. Therapy with HCQ significantly reduced the severity of atherosclerosis in CKD mice and sham treated mice. HCQ reduced the area of aortic atherosclerosis on en face examination by approximately 60% in HCQ treated groups compared to the non-treated groups. Additionally, therapy with HCQ resulted in significant reduction in vascular endothelial dysfunction with improvement in vascular elasticity and flow patterns and better-preserved vascular wall thickness across multiple vascular beds. More importantly, we found that presence of CKD had no mitigating effect on HCQ’s anti-atherosclerotic and vasculoprotective effects. These beneficial effects were not due to any significant effect of HCQ on inflammation, renal function, or lipid profile at the end of 16 weeks of therapy. This study, which demonstrates structural and functional protection against atherosclerosis by HCQ, provides a rationale to evaluate its use in CKD patients. Further studies are needed to define the exact mechanisms through which HCQ confers these benefits. PMID:26414017

  2. Plasma suppression of beamstrahlung

    SciTech Connect

    Whittum, D.H.; Sessler, A.M.; Stewart, J.J.; Yu, S.S.

    1988-06-01

    We investigate the use of a plasma at the interaction point of two colliding beams to suppress beamsstrahlung and related phenomena. We derive conditions for good current cancellation via plasma return currents and report on numerical simulations conducted to confirm our analytic results. 10 refs., 5 figs., 4 tabs.

  3. Parasitic suppressing circuit

    NASA Technical Reports Server (NTRS)

    Fowler, J. T.; Raposa, F. L. (inventors)

    1973-01-01

    A circuit for suppressing parasitic oscillations across an inductor operating in a resonant mode is described. The circuit includes a switch means and resistive means connected serially across the inductor. A unidirectional resistive-capacitive network is also connected across the inductor and to the switch means to automatically render the switch means conducting when inductive current through the inductor ceases to flow.

  4. Mitral and aortic valve sclerosis/calcification and carotid atherosclerosis: results from 1065 patients.

    PubMed

    Rossi, Andrea; Faggiano, Pompilio; Amado, Alexandra E; Cicoira, Mariantonietta; Bonapace, Stefano; Franceschini, Lorenzo; Dini, Frank L; Ghio, Stefano; Agricola, Eustachio; Temporelli, Pier Luigi; Vassanelli, Corrado

    2014-11-01

    This study assesses whether aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are associated with carotid artery atherosclerosis, independently of traditional cardiovascular risk factors. A total of 1065 patients underwent both echocardiography and carotid artery ultrasound scanning. AVS and MAC were defined as focal areas of increased echogenicity and thickening of the aortic leaflets or mitral valve annulus. Carotid artery atherosclerosis was defined as presence/absence of any atherosclerotic plaque or presence/absence of plaque >50 %. Of 1065 patients (65 ± 9 years; 38 % female) who comprised the study population, 642 (60 %) had at least one atherosclerotic plaque. AVS, but not mitral valve sclerosis; was associated with the presence of carotid atherosclerosis (odds ratio (OR) 1.9, 95 % confidence interval (CI) 1.2-3.9; P = 0.005) and the degree of carotid atherosclerosis (OR 2.1, 95 % CI 1.2-3.9; P = 0.01) in a multivariate model including age, gender, previous ischemic heart disease, hypertension, dyslipidemia, smoking, diabetes, family cardiovascular history, left ventricular size, mass, and ejection fraction, and left atrial size. AVS is a significant predictor of carotid atherosclerosis, independently of other cardiovascular clinical and echocardiographic risk factors. PMID:24196525

  5. Prevalence of Atherosclerosis in diabetic and non-diabetic patients with rheumatoid arthritis

    PubMed Central

    Kisiel, Bart?omiej; Kruszewski, Robert; Juszkiewicz, Aleksandra; K?os, Krzysztof; T?ustochowicz, Ma?gorzata; T?ustochowicz, Witold

    2015-01-01

    Objectives: (1) To compare the prevalence of preclinical atherosclerosis in diabetic vs. non-diabetic rheumatoid arthritis (RA) patients; (2) to determine the influence of classical and RA-related factors on atherosclerosis; (3) to assess the usefulness of combined carotid and femoral ultrasonography in detecting atherosclerosis. Methods: The study comprised 42 non-diabetic RA patients, 42 diabetic RA patients and 42 controls. Intima media thickness (IMT) was measured in the common carotid and superficial femoral arteries. These vessels were screened for atherosclerotic plaque. Results: Plaque was more prevalent in diabetic RA patients than in non-diabetic RA patients or controls. Carotid IMT and femoral IMT were higher in diabetic RA patients compared to controls. So was femoral IMT in diabetic compared to non-diabetic RA patients. The prevalence of increased IMT and plaque was comparable in carotid ultrasonography and combined carotid and femoral ultrasonography in all groups. Conclusions: Subclinical atherosclerosis was found to be higher in diabetic RA patients than in non-diabetic RA patients. The combination of carotid and femoral artery ultrasonography did not improve the detection of atherosclerosis in RA.

  6. Possible Therapeutic Effect of Stem Cell in Atherosclerosis in Albino Rats. A Histological and Immunohistochemical Study

    PubMed Central

    Abdel-Kawi, Samraa H; Hashem, Khalid S

    2015-01-01

    Background Atherosclerosis is the leading cause of death worldwide. there are no effective approaches to regressing atherosclerosis due to not fully understood mechanisms. Recently, stem cell-based therapies have held promises to various diseases, including vascular diseases. Aim The present study aimed at investigating the possible effect of cord blood mesenchymal stem cell (MSC) therapy on atherosclerosis. Material and Methods Eighty adult male albino rats were divided into control group (I), atherogenic group (II): subjected to high cholesterol fed diet (200~300 mg/kg body weight) for 12 weeks and 1.8 million units of vitamin D / kg of diet for 6 weeks. Stem cell therapy group (III): injected with stem cells in the tail vein following confirmation of atherosclerosis. Histological, Immunohistochemical and morphometric studies were performed were conducted. Results Atherogenic group (II) showed increased aortic thickness, intimal proliferation, smooth muscle proliferation and migration. Increased area % of collagen fibers, iNOS and vimentin immunoreactions were recorded and proved morphometrically. All findings regressed on stem cell therapy. Conclusion A definite therapeutic effect of mesenchymal stem cells was found on atherosclerosis. PMID:26634068

  7. Angiopoietin-like 4: A double-edged sword in atherosclerosis and ischemic stroke?

    PubMed

    Xu, Liang; Guo, Zhen-Ni; Yang, Yi; Xu, Jun; Burchell, Sherrefa R; Tang, Jiping; Zhang, Jianmin; Xu, Jing; Zhang, John H

    2015-10-01

    Ischemic stroke is one of the leading causes of death in the world, and thus is a major public health concern. Atherosclerosis, also known as atherogenesis, is a crucial risk factor for cerebral ischemia, yet how it develops remains largely unknown. It has been found, however, that angiopoietin-like protein 4 (ANGPTL4), a protein expressed in vascular endothelial cells, plays a role in the pathophysiology of atherosclerosis and may therefore be involved in ischemic stroke. ANGPTL4 activity is associated with endothelial cell integrity, inflammation, oxidative stress, and lipid metabolism. ANGPTL4 also serves as a potent inhibitor of the lipoprotein lipase, and may inhibit atherogenesis via regulating inflammatory signaling and lipid metabolism. In addition, ANGPTL4 plays a role in the regulation of oxidative stress. However, there currently exists a controversy on the role of ANGPTL4 in endothelial cells. Some studies indicate that ANGPTL4 can protect the integrity of endothelial cells, while others have shown that it can be destructive to the endothelium, thereby leading to the initiation of atherosclerosis. Thus, the effects of ANGPTL4 on development of atherosclerosis and thereby ischemic stroke, are undefined. Further research is needed to better understand ANGPTL4-mediated signaling pathways in endothelial function and to determine its potentials as therapeutic target for atherosclerosis and ischemic stroke. PMID:26033474

  8. Very low levels of HDL cholesterol and atherosclerosis, a variable relationship – a review of LCAT deficiency

    PubMed Central

    Savel, Julia; Lafitte, Marianne; Pucheu, Yann; Pradeau, Vincent; Tabarin, Antoine; Couffinhal, Thierry

    2012-01-01

    A number of epidemiological and clinical studies have demonstrated that plasma high-density lipoprotein (HDL) level is a strong inverse predictor of cardiovascular events. HDL is believed to retard the formation of atherosclerotic lesions by removing excess cholesterol from cells and preventing endothelial dysfunction. Lecithin cholesterol acyltransferase (LCAT) plays a central role in the formation and maturation of HDL, and in the intravascular stage of reverse cholesterol transport: a major mechanism by which HDL modulates the development and progression of atherosclerosis. A defect in LCAT function would be expected to enhance atherosclerosis, by interfering with the reverse cholesterol transport step. As such, one would expect to find more atherosclerosis and cardiovascular events in LCAT-deficient patients. But this relationship is not always evident. In this review, we describe contradictory reports in the literature about cardiovascular risks in this patient population. We discuss the paradoxical finding of severe HDL deficiency and an absence of subclinical atherosclerosis in LCAT-deficient patients, which has been used to reject the hypothesis that HDL level is important in the protection against atherosclerosis. Furthermore, to illustrate this paradoxical finding, we present a case study of one patient, referred for evaluation of global cardiovascular risk in the presence of a low HDL cholesterol level, who was diagnosed with LCAT gene mutations. PMID:22701329

  9. Mannose binding lectin gene polymorphism and preclinical carotid atherosclerosis in patients with systemic lupus erythematosus.

    PubMed

    El-Sherif, Wafaa T; Herdan, Omar M; Osman, Mustafa H; Alkady, Eman A M

    2010-01-01

    Patients with systemic lupus erythematosus (SLE) have increased risk of atherosclerosis and CVD that cannot be explained by traditional risk factors. Previous studies indicated that mannose binding lectin (MBL) may modify the development of atherosclerosis. This study was designed to investigate association of MBL gene polymorphism with occurrence of preclinical atherosclerosis in SLE. The study included 46 patients with SLE and 17 age and sex matched controls. MBL2 genotypes were assessed in patients and controls by the PCR-RFLP method and intima-media thickness of the common carotid artery (cclMT) was determined by means of ultrasonography. Also, serological markers were measured and the disease activity index (SLEDAI) was estimated. SLE patients had higher frequency of MBL A/B + B/B genotypes (47.8%) than controls (29.4%). ccIMT was higher in patients having A/B, B/B, A/B+B/B genotypes when compared with wild genotype (A/A). Patients with A/B+B/B genotypes showed high serum level of LDL, TG, ESRI, CRP and SLEDAI score, but low level of HDL, C3, and C4 compared to wild genotype. ccIMT of mutant SLE subgroup correlated well with SLE risk factors for atherosclerosis. In conclusion, mutant genotypes of MBL may be atherogenic as SLE patients had a higher IMT, which correlated significantly with SLE risk factors for atherosclerosis. PMID:23082493

  10. Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

    PubMed Central

    Busso, Dolores; Mascareño, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolás; Quiroz, Alonso; Amigo, Ludwig; Valdés, Gloria; Rigotti, Attilio

    2014-01-01

    The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000?UI of ?-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

  11. LDL particle core enrichment in cholesteryl oleate increases proteoglycan binding and promotes atherosclerosis[S

    PubMed Central

    Melchior, John T.; Sawyer, Janet K.; Kelley, Kathryn L.; Shah, Ramesh; Wilson, Martha D.; Hantgan, Roy R.; Rudel, Lawrence L.

    2013-01-01

    Several studies in humans and animals suggest that LDL particle core enrichment in cholesteryl oleate (CO) is associated with increased atherosclerosis. Diet enrichment with MUFAs enhances LDL CO content. Steroyl O-acyltransferase 2 (SOAT2) is the enzyme that catalyzes the synthesis of much of the CO found in LDL, and gene deletion of SOAT2 minimizes CO in LDL and protects against atherosclerosis. The purpose of this study was to test the hypothesis that the increased atherosclerosis associated with LDL core enrichment in CO results from an increased affinity of the LDL particle for arterial proteoglycans. ApoB-100-only Ldlr?/? mice with and without Soat2 gene deletions were fed diets enriched in either cis-MUFA or n-3 PUFA, and LDL particles were isolated. LDL:proteogylcan binding was measured using surface plasmon resonance. Particles with higher CO content consistently bound with higher affinity to human biglycan and the amount of binding was shown to be proportional to the extent of atherosclerosis of the LDL donor mice. The data strongly support the thesis that atherosclerosis was induced through enhanced proteoglycan binding of LDL resulting from LDL core CO enrichment. PMID:23804810

  12. Association of Early Atherosclerosis with Vascular Wall Shear Stress in Hypercholesterolemic Zebrafish

    PubMed Central

    Lee, Sang Joon; Choi, Woorak; Seo, Eunseok; Yeom, Eunseop

    2015-01-01

    Although atherosclerosis is a multifactorial disease, the role of hemodynamic information has become more important. Low and oscillating wall shear stress (WSS) that changes its direction is associated with the early stage of atherosclerosis. Several in vitro and in vivo models were proposed to reveal the relation between the WSS and the early atherosclerosis. However, these models possess technical limitations in mimicking real physiological conditions and monitoring the developmental course of the early atherosclerosis. In this study, a hypercholesterolaemic zebrafish model is proposed as a novel experimental model to resolve these limitations. Zebrafish larvae are optically transparent, which enables temporal observation of pathological variations under in vivo condition. WSS in blood vessels of 15 days post-fertilisation zebrafish was measured using a micro particle image velocimetry (PIV) technique, and spatial distribution of lipid deposition inside the model was quantitatively investigated after feeding high cholesterol diet for 10 days. Lipids were mainly deposited in blood vessel of low WSS. The oscillating WSS was not induced by the blood flows in zebrafish models. The present hypercholesterolaemic zebrafish would be used as a potentially useful model for in vivo study about the effects of low WSS in the early atherosclerosis. PMID:26561854

  13. Once Upon a Time: The Adaptive Immune Response in Atherosclerosis—a Fairy Tale No More

    PubMed Central

    Le Borgne, Marie; Caligiuri, Giuseppina; Nicoletti, Antonino

    2015-01-01

    Extensive research has been carried out to decipher the function of the adaptive immune response in atherosclerosis, with the expectation that it will pave the road for the design of immunomodulatory therapies that will prevent or reverse the progression of the disease. All this work has led to the concept that some T- and B-cell subsets are proatherogenic, whereas others are atheroprotective. In addition to the immune response occurring in the spleen and lymph nodes, it has been shown that lymphoid neo-genesis takes place in the adventitia of atherosclerotic vessels, leading to the formation of tertiary lymphoid organs where an adaptive immune response can be mounted. Whereas the mechanisms orchestrating the formation of these organs are becoming better understood, their impact on atherosclerosis progression remains unclear. Several potential therapeutic strategies against atherosclerosis, such as protective vaccination against atherosclerosis antigens or inhibiting the activation of proatherogenic B cells, have been proposed based on our improving knowledge of the role of the immune system in atherosclerosis. These strategies have shown success in preclinical studies, giving hope that they will lead to clinical applications. PMID:26605642

  14. Once Upon a Time: The Adaptive Immune Response in Atherosclerosis-a Fairy Tale No More.

    PubMed

    Le Borgne, Marie; Caligiuri, Giuseppina; Nicoletti, Antonino

    2015-01-01

    Extensive research has been carried out to decipher the function of the adaptive immune response in atherosclerosis, with the expectation that it will pave the road for the design of immunomodulatory therapies that will prevent or reverse the progression of the disease. All this work has led to the concept that some T- and B-cell subsets are proatherogenic, whereas others are atheroprotective. In addition to the immune response occurring in the spleen and lymph nodes, it has been shown that lymphoid neo-genesis takes place in the adventitia of atherosclerotic vessels, leading to the formation of tertiary lymphoid organs where an adaptive immune response can be mounted. Whereas the mechanisms orchestrating the formation of these organs are becoming better understood, their impact on atherosclerosis progression remains unclear. Several potential therapeutic strategies against atherosclerosis, such as protective vaccination against atherosclerosis antigens or inhibiting the activation of proatherogenic B cells, have been proposed based on our improving knowledge of the role of the immune system in atherosclerosis. These strategies have shown success in preclinical studies, giving hope that they will lead to clinical applications. PMID:26605642

  15. Insulin resistance and hypertension: the Insulin Resistance Atherosclerosis study.

    PubMed

    Saad, Mohammed F; Rewers, Marian; Selby, Joseph; Howard, George; Jinagouda, Sujata; Fahmi, Salwa; Zaccaro, Dan; Bergman, Richard N; Savage, Peter J; Haffner, Steven M

    2004-06-01

    The association between insulin resistance and insulinemia and hypertension is controversial. We examined the relation between insulin resistance and hypertension in 564 non-Hispanic whites (NHW), 505 Hispanics (H), and 413 African Americans (AA) who participated in the Insulin Resistance Atherosclerosis Study (IRAS). Insulin sensitivity was measured with a frequently sampled intravenous glucose tolerance test with minimal model analysis. The prevalence of hypertension was 32.5%, 49.4%, and 32.3% in NHW, AA, and H, respectively (P<0.001). When subjects without diabetes in all ethnic groups were combined, age, male sex, race (AA), body mass index (BMI), and insulin resistance, but not fasting insulin, were significantly associated with hypertension. When each ethnic group was analyzed separately, insulin resistance was significantly associated with hypertension in NHW and H, but not AA. After excluding subjects taking antihypertensive medications, male sex, BMI, fasting glucose, and insulin resistance, but not fasting insulin, were significant determinants of blood pressure. When the 3 ethnic groups were analyzed separately, insulin resistance was significantly associated with blood pressure in H, but not NHW, or AA. Neither insulin resistance nor fasting insulin was significantly associated with hypertension or blood pressure in subjects with diabetes of the 3 ethnic groups after adjusting for age, sex, BMI, and waist. In conclusion, insulin resistance, but not insulinemia, was related to hypertension and blood pressure in subjects without diabetes, but ethnic differences in these relations appear to exist. Neither insulin resistance nor insulinemia was related to hypertension or blood pressure in patients with type 2 diabetes in the 3 ethnic groups. PMID:15123571

  16. Novel agents to manage dyslipidemias and impact atherosclerosis.

    PubMed

    Nachimuthu, S; Raggi, P

    2006-09-01

    Strong epidemiological evidence linked elevated levels of low-density lipoprotein cholesterol (LDL-C) to risk of atherosclerotic heart disease. As a consequence, LDL-C lowering has been the main goal of therapy to reduce cardiovascular risk for the past few decades and hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have become some of the most commonly prescribed drugs. In spite of the proven efficacy of these drugs, statins reduce cardiovascular events by only 30-40%. Epidemiological analyses clearly indicate that a significant portion of risk is linked to other particles such as low high-density lipoprotein cholesterol (HDL-C), high triglycerides and others. Furthermore, several quantitative coronary angiography studies showing regression of atherosclerosis and reduction in subsequent events utilized a combination of drugs effective on LDL-C as well as other lipoproteins. Hence, several new drugs are being investigated that affect more than the traditional LDL-C pathways. In this article, we review lipoprotein-modifying agents that have either been recently released, or are still in various phases of development. They include agents that reduce LDL-C levels by mechanisms other than HMG-CoA inhibition (such as cholesterol absorption inhibitors, Acyl-CoA cholesterol acyl transferase inhibitors, sterol-regulating binding protein cleavage activating protein ligands, microsomal triglyceride transfer protein inhibitors, LDL-C receptor activators and farnesoid X receptor antagonists) and agents that raise HDL-C cholesterol or improve cholesterol efflux (such as cholesterol ester transfer protein inhibitors, retinoid X receptor selective agonists, specific peroxisome proliferator-activated receptor (PPAR) agonists and estrogen like compounds). PMID:17017903

  17. Ezetimibe Attenuates Atherosclerosis Associated with Lipid Reduction and Inflammation Inhibition

    PubMed Central

    Tie, Chunmiao; Gao, Kanglu; Zhang, Na; Zhang, Songzhao; Shen, Jiali; Xie, Xiaojie; Wang, Jian-an

    2015-01-01

    Background Ezetimibe, as a cholesterol absorption inhibitor, has been shown protecting against atherosclerosis when combined with statin. However, side by side comparison has not been made to evaluate the beneficial effects of ezetimibe alone versus statin. Herein, the study aimed to test whether ezetimibe alone would exhibit similar effects as statin and the combination therapy would be necessary in a moderate lesion size. Methods and Results ApoE-/- male mice that were fed a saturated-fat supplemented diet were randomly assigned to different therapeutic regimens: vehicle, ezetimibe alone (10 mg/kg/day), atorvastatin (20 mg/kg/day) or combination of ezetimibe and atorvastatin through the drinking water. On 28 days, mice were sacrificed and aorta and sera were collected to analyze the atherosclerotic lesion and blood lipid and cholesterol levels. As a result, ezetimibe alone exerted similar protective effects on atherosclerotic lesion sizes as atorvastatin, which was mediated by lowering serum cholesterol concentrations, inhibiting macrophage accumulation in the lesions and reducing circulatory inflammatory cytokines, such as monocyte chemoattractant protein (MCP-1) and tumor necrosis factor (TNF-?). In contrast to ezetimibe administration, atorvastatin alone attenuated atherosclerotic lesion which is dependent on its anti-inflammation effects. There were no significance differences in lesion areas and serum concentrations of cholesterol, oxidized LDL and inflammatory cytokines between combination therapy and monotherapy (either ezetimibe or atorvastatin). There were significant correlations between the lesion areas and serum concentrations of cholesterol, MCP-1 and TNF-?, respectively. However, there were no significant correlations between the lesion areas and serum concentrations of TGF-?1 and oxLDL. Conclusions Ezetimibe alone played the same protection against a moderate atherosclerotic lesion as atorvastatin, which was associated with lowering serum cholesterol, decreasing circulating inflammatory cytokines, and inhibiting macrophage accumulation in the lesions. PMID:26555472

  18. Pressure suppression containment system

    DOEpatents

    Gluntz, D.M.; Townsend, H.E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of-coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto. 6 figures.

  19. Pressure suppression containment system

    DOEpatents

    Gluntz, Douglas M. (San Jose, CA); Townsend, Harold E. (San Jose, CA)

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto.

  20. Nonsense suppression in archaea.

    PubMed

    Bhattacharya, Arpita; Köhrer, Caroline; Mandal, Debabrata; RajBhandary, Uttam L

    2015-05-12

    Bacterial strains carrying nonsense suppressor tRNA genes played a crucial role in early work on bacterial and bacterial viral genetics. In eukaryotes as well, suppressor tRNAs have played important roles in the genetic analysis of yeast and worms. Surprisingly, little is known about genetic suppression in archaea, and there has been no characterization of suppressor tRNAs or identification of nonsense mutations in any of the archaeal genes. Here, we show, using the ?-gal gene as a reporter, that amber, ochre, and opal suppressors derived from the serine and tyrosine tRNAs of the archaeon Haloferax volcanii are active in suppression of their corresponding stop codons. Using a promoter for tRNA expression regulated by tryptophan, we also show inducible and regulatable suppression of all three stop codons in H. volcanii. Additionally, transformation of a ?pyrE2 H. volcanii strain with plasmids carrying the genes for a pyrE2 amber mutant and the serine amber suppressor tRNA yielded transformants that grow on agar plates lacking uracil. Thus, an auxotrophic amber mutation in the pyrE2 gene can be complemented by expression of the amber suppressor tRNA. These results pave the way for generating archaeal strains carrying inducible suppressor tRNA genes on the chromosome and their use in archaeal and archaeviral genetics. We also provide possible explanations for why suppressor tRNAs have not been identified in archaea. PMID:25918386

  1. Nonsense suppression in archaea

    PubMed Central

    Bhattacharya, Arpita; Köhrer, Caroline; Mandal, Debabrata; RajBhandary, Uttam L.

    2015-01-01

    Bacterial strains carrying nonsense suppressor tRNA genes played a crucial role in early work on bacterial and bacterial viral genetics. In eukaryotes as well, suppressor tRNAs have played important roles in the genetic analysis of yeast and worms. Surprisingly, little is known about genetic suppression in archaea, and there has been no characterization of suppressor tRNAs or identification of nonsense mutations in any of the archaeal genes. Here, we show, using the ?-gal gene as a reporter, that amber, ochre, and opal suppressors derived from the serine and tyrosine tRNAs of the archaeon Haloferax volcanii are active in suppression of their corresponding stop codons. Using a promoter for tRNA expression regulated by tryptophan, we also show inducible and regulatable suppression of all three stop codons in H. volcanii. Additionally, transformation of a ?pyrE2 H. volcanii strain with plasmids carrying the genes for a pyrE2 amber mutant and the serine amber suppressor tRNA yielded transformants that grow on agar plates lacking uracil. Thus, an auxotrophic amber mutation in the pyrE2 gene can be complemented by expression of the amber suppressor tRNA. These results pave the way for generating archaeal strains carrying inducible suppressor tRNA genes on the chromosome and their use in archaeal and archaeviral genetics. We also provide possible explanations for why suppressor tRNAs have not been identified in archaea. PMID:25918386

  2. Imaging Atherosclerosis with Hybrid Positron Emission Tomography/Magnetic Resonance Imaging

    PubMed Central

    Kjær, Andreas

    2015-01-01

    Noninvasive imaging of atherosclerosis could potentially move patient management towards individualized triage, treatment, and followup. The newly introduced combined positron emission tomography (PET) and magnetic resonance imaging (MRI) system could emerge as a key player in this context. Both PET and MRI have previously been used for imaging plaque morphology and function: however, the combination of the two methods may offer new synergistic opportunities. Here, we will give a short summary of current relevant clinical applications of PET and MRI in the setting of atherosclerosis. Additionally, our initial experiences with simultaneous PET/MRI for atherosclerosis imaging are presented. Finally, future potential vascular applications exploiting the unique combination of PET and MRI will be discussed. PMID:25695091

  3. Echium Oil Reduces Atherosclerosis in apoB100-only LDLrKO Mice

    PubMed Central

    Forrest, Lolita M.; Boudyguina, Elena; Wilson, Martha D.; Parks, John S.

    2012-01-01

    Introduction The anti-atherogenic and hypotriglyceridemic properties of fish oil are attributed to its enrichment in eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides. Objective We used apoB100 only, LDLrKO mice to investigate whether echium oil reduces atherosclerosis. Methods Mice were fed palm, echium, or fish oil-containing diets for 16 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. Results Compared to palm oil, echium oil feeding resulted in significantly less plasma triglyceride and cholesterol levels, and atherosclerosis, comparable to that of fish oil. Conclusion This is the first report that echium oil is anti-atherogenic, suggesting that it may be a botanical alternative to fish oil for atheroprotection. PMID:22100249

  4. The role of DNA damage and repair in atherosclerosis: A review.

    PubMed

    Shah, Nikunj R; Mahmoudi, Michael

    2015-09-01

    The global burden of cardiovascular disease is increasing despite therapeutic advances in medication and interventional technologies. Accumulated deoxyribonucleic acid (DNA) damage and subsequent repair pathways are now increasingly recognised as a causal factor in the initiation and progression of atherosclerosis. These molecular alterations have been shown to occur within affected vasculature, plaque microenvironment as well as in circulating cells. The DNA damage response (DDR) pathway is reliant on post-translational modification of sensing proteins which activate a signalling cascade to repair, if possible, DNA damaged sites in response to various environmental and physiological insults. This review summarises the current evidence for DNA damage in atherosclerosis, the key steps involved in the DDR pathway, DNA repair and their subsequent effects on atherosclerotic plaques, as well as the therapeutic options in managing DNA damage-induced atherosclerosis. PMID:26211712

  5. Research advances in the relationship between nonalcoholic fatty liver disease and atherosclerosis.

    PubMed

    Xu, Xin; Lu, Linlin; Dong, Quanyong; Li, Xiaolin; Zhang, Nannan; Xin, Yongning; Xuan, Shiying

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a metabolic stress-induced liver disease that is closely related not only to genetic susceptibility but also to insulin resistance and highly linked with metabolic syndrome. In recent years, the prevalence of NAFLD has increased rapidly, paralleling the epidemic of type 2 diabetes mellitus and obesity leading to cardiovascular disease. It has been demonstrated that NAFLD is highly associated with atherosclerosis. With recently gained knowledge, it appears that NAFLD may induce insulin resistance, dyslipidemia, oxidative stress, inflammation, and fluctuation of adipokines associated with atherosclerosis. In this review, we aimed to summarize recent discoveries related to both NAFLD and atherosclerosis, and to identify possible mechanisms linking them. PMID:26631018

  6. Cav1.2, Cell Proliferation, and New Target in Atherosclerosis

    PubMed Central

    Soldatov, Nikolai M.

    2013-01-01

    Cav1.2 calcium channels are the principal proteins involved in electrical, mechanical, and/or signaling functions of the cell. Cav1.2 couples membrane depolarization to the transient increase in intracellular Ca2+ concentration that is a trigger for muscle contraction and CREB-dependent transcriptional activation. The CACNA1C gene coding for the Cav1.2 pore-forming ?1C subunit is subject to extensive alternative splicing. This review is the first attempt to follow the association between cell proliferation, Cav1.2 expression and splice variation, and atherosclerosis. Based on insights into the association between the atherosclerosis-induced molecular remodeling of Cav1.2, proliferation of vascular smooth muscle cells, and CREB-dependent transcriptional signaling, this review will give a perspective outlook for the use of the CACNA1C exon skipping as a new potential gene therapy approach to atherosclerosis. PMID:25937960

  7. AIBP: A Novel Molecule at the Interface of Cholesterol Transport, Angiogenesis, and Atherosclerosis

    PubMed Central

    Zhu, Laurence; Fang, Longhou

    2015-01-01

    Cardiovascular disease, which is often driven by hypercholesterolemia and subsequent coronary atherosclerosis, is the number-one cause of morbidity and mortality in the United States. Based on long-term epidemiological studies, high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with risk for coronary artery disease (CAD). HDL-mediated reverse cholesterol transport (RCT) is responsible for cholesterol removal from the peripheral tissues and return to the liver for final elimination.1 In atherosclerosis, intraplaque angiogenesis promotes plaque growth and increases plaque vulnerability. Conceivably, the acceleration of RCT and disruption of intraplaque angiogenesis would inhibit atherosclerosis and reduce CAD. We have identified a protein called apoA-I binding protein (AIBP) that augments HDL functionality by accelerating cholesterol efflux. Furthermore, AIBP inhibits vascular endothelial growth factor receptor 2 activation in endothelial cells and limits angiogenesis.2 The following discusses the prospect of using AIBP as a novel therapeutic approach for the treatment of CAD.

  8. Using multimodal femtosecond CARS imaging to determine plaque burden in luminal atherosclerosis

    NASA Astrophysics Data System (ADS)

    Ko, Alex C.-T.; Mostaço-Guidolin, Leila B.; Ridsdale, Andrew; Pegoraro, Adrian F.; Smith, Michael S. D.; Slepkov, Aaron; Hewko, Mark D.; Kohlenberg, Elicia K.; Schattka, Bernie; Stolow, Albert; Sowa, Michael G.

    2011-03-01

    Luminal atherosclerosis imaging was demonstrated by multimodal femtosecond CARS microscopy (MM-CARS). Using a myocardial infarction-prone rabbit model of atherosclerosis, this study demonstrated the utility of multimodal CARS imaging in determining atherosclerotic plaque burden through two types of image analysis procedures. Firstly, multimodal CARS images were evaluated using a signal-intensity parameter based on intensity changes derived from the multi-channel data (e.g. TPEF, SHG and CARS) to classify plaque burden within the vessel. Secondly, the SHG images that mainly correspond to collagen fibrils were evaluated using a texture analysis model based on the first-order statistical (FOS) parameters of the image histogram. Correlation between FOS parameters of collagen images with atherosclerosis plaque burden was established. A preliminary study of using spectroscopic CARS in identifying the different lipid components within the plaque was also discussed.

  9. Tocotrienol enriched palm oil prevents atherosclerosis through modulating the activities of peroxisome proliferators-activated receptors.

    PubMed

    Li, Fengjuan; Tan, Wenjuan; Kang, Zhanfang; Wong, Chi-Wai

    2010-07-01

    Palm oil is enriched in vitamin E in the form of alpha-, gamma-, and delta-tocotrienols. Dietary tocotrienol supplements have been shown to prevent atherosclerosis development in patients and preclinical animal models. However, the mechanistic basis for this health beneficial effect is not well established. Peroxisome proliferator-activated receptors alpha, gamma, and delta (PPARalpha, PPARgamma, and PPARdelta) are ligand regulated transcription factors that play essential preventive roles in the development of atherosclerosis through regulating energy metabolism and inflammation. In this study, we presented data that the tocotrienol rich fraction (TRF) of palm oil activated PPARalpha, PPARgamma, and PPARdelta in reporter based assays. Importantly, TRF attenuated the development of atherosclerosis in ApoE-/- mice through inducing PPAR target gene liver X receptor alpha (LXRalpha) and its down-stream target genes apolipoproteins and cholesterol transporters, suggesting that modulating the activities of PPARs is a key aspect of the in vivo action of tocotrienols. PMID:20138624

  10. Wall Shear Stress Characteristics for the Progression of the Disease, Atherosclerosis

    NASA Astrophysics Data System (ADS)

    Goswami, P.; Mandal, D. K.; Manna, N. K.; Chakrabarti, S.

    2014-12-01

    Wall shear stress (WSS) characteristics of a stenosed artery which are the important physiological parameters for the progression of the arterial diseases atherosclerosis, are studied and compared for different Reynolds numbers and different Womersley numbers. Numerical simulations of physiological pulsatile flow through a model stenotic artery are performed by finite volume method. From this study, it is revealed that the chance of formation of atherosclerosis increases with increase in Reynolds number and decreases with increase in Womersley number. The phenomenon of mass transportation across arterial wall is more in case of increase in Womersley number rather than Reynolds number. The chance of formation of atheromatous plaque will be high with higher Reynolds number and Womersley number. In the low WSS region, high magnitude of Womersley number indicates high chance of progression of the disease atherosclerosis. High magnitude of Womersley number with low Reynolds number is more dangerous for the progression of the disease in the low WSS region.

  11. Computed tomographic evidence of atherosclerosis in the mummified remains of humans from around the world.

    PubMed

    Thompson, Randall C; Allam, Adel H; Zink, Albert; Wann, L Samuel; Lombardi, Guido P; Cox, Samantha L; Frohlich, Bruno; Sutherland, M Linda; Sutherland, James D; Frohlich, Thomas C; King, Samantha I; Miyamoto, Michael I; Monge, Janet M; Valladolid, Clide M; El-Halim Nur El-Din, Abd; Narula, Jagat; Thompson, Adam M; Finch, Caleb E; Thomas, Gregory S

    2014-06-01

    Although atherosclerosis is widely thought to be a disease of modernity, computed tomographic evidence of atherosclerosis has been found in the bodies of a large number of mummies. This article reviews the findings of atherosclerotic calcifications in the remains of ancient people-humans who lived across a very wide span of human history and over most of the inhabited globe. These people had a wide range of diets and lifestyles and traditional modern risk factors do not thoroughly explain the presence and easy detectability of this disease. Nontraditional risk factors such as the inhalation of cooking fire smoke and chronic infection or inflammation might have been important atherogenic factors in ancient times. Study of the genetic and environmental risk factors for atherosclerosis in ancient people may offer insights into this common modern disease. PMID:25667088

  12. Hyperglycemia suppresses ABCA1 expression in vascular smooth muscle cells.

    PubMed

    Yu, X; Murao, K; Imachi, H; Li, J; Nishiuchi, T; Hosomi, N; Masugata, H; Zhang, G X; Iwama, H; Ishida, T

    2010-04-01

    Hyperglycemia is a major risk factor for atherosclerotic disease. The ATP-binding cassette transporter A1 (ABCA1) functions as a pivotal regulator of lipid efflux from cells to apolipoproteins and is thus involved in lowering the risk of atherosclerosis. In this study, we have examined the glucose-mediated regulation of the ABCA1 gene expression in vascular smooth muscle cells. ABCA1 expression was examined by real-time polymerase chain reaction (PCR), Western blot analysis, and reporter gene assay. The results showed that the expression of the ABCA1 mRNA and protein decreased after the cells were treated with 22.4 mM glucose for 48 h. The transcriptional activity of the ABCA1 promoter paralleled the endogenous expression of the ABCA1 gene. Next, we used inhibitors of certain signal transduction pathways to demonstrate that the glucose-induced ABCA1 suppression is sensitive to the p38-mitogen-activated protein kinase (MAPK) inhibitors. The expression of a constitutively active form of p38-MAPK in the cells inhibited the ABCA1 promoter activity, irrespective of the presence of glucose. A dominant-negative mutant of p38-MAPK abrogated the inhibitory effect of glucose on the ABCA1 promoter activity. These results indicate that the glucose-induced suppression of ABCA1 expression is partially mediated by the activation of the p38-MAPK pathway. PMID:20101560

  13. 75 FR 63488 - Submission for OMB Review; Comment Request; Multi-Ethnic Study of Atherosclerosis (MESA) Event...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-15

    ... SERVICES National Institutes of Health Submission for OMB Review; Comment Request; Multi-Ethnic Study of Atherosclerosis (MESA) Event Surveillance SUMMARY: Under the provisions of Section 3507(a)(1)(D) of the Paperwork...: Multi-Ethnic Study of Atherosclerosis (MESA) Event Surveillance. Type of Information Request:...

  14. VARIANTS AT THE APOA5 LOCUS, ASSOCIATION WITH CAROTID ATHEROSCLEROSIS, AND MODIFICATION BY OBESITY: THE FRAMINGHAM STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Genetic variation at the apolipoprotein A5 (APOA5) locus is associated with elevated triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common AP...

  15. The small leucine-rich repeat proteoglycans in tissue repair and atherosclerosis.

    PubMed

    Hultgårdh-Nilsson, A; Borén, J; Chakravarti, S

    2015-11-01

    Proteoglycans consist of a protein core with one or more covalently attached glycosaminoglycan (GAG) side chains and have multiple roles in the initiation and progression of atherosclerosis. Here we discuss the potential and known functions of a group of small leucine-rich repeat proteoglycans (SLRPs) in atherosclerosis. We focus on five SLRPs, decorin, biglycan, lumican, fibromodulin and PRELP, because these have been detected in atherosclerotic plaques or demonstrated to have a role in animal models of atherosclerosis. Decorin and biglycan are modified post-translationally by substitution with chondroitin/dermatan sulphate GAGs, whereas lumican, fibromodulin and PRELP have keratan sulphate side chains, and the core proteins have leucine-rich repeat (LRR) motifs that are characteristic of the LRR superfamily. The chondroitin/dermatan sulphate GAG side chains have been implicated in lipid retention in atherosclerosis. The core proteins are discussed here in the context of (i) interactions with collagens and their implications in tissue integrity, fibrosis and wound repair and (ii) interactions with growth factors, cytokines, pathogen-associated molecular patterns and cell surface receptors that impact normal physiology and disease processes such as inflammation, innate immune responses and wound healing (i.e. processes that are all important in plaque development and progression). Thus, studies of these SLRPs in the context of wound healing are providing clues about their functions in early stages of atherosclerosis to plaque vulnerability and cardiovascular disease at later stages. Understanding of signal transduction pathways regulated by the core protein interactions is leading to novel roles and therapeutic potential for these proteins in wound repair and atherosclerosis. PMID:26477596

  16. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice

    PubMed Central

    Fagman, Johan B.; Wilhelmson, Anna S.; Motta, Benedetta M.; Pirazzi, Carlo; Alexanderson, Camilla; De Gendt, Karel; Verhoeven, Guido; Holmäng, Agneta; Anesten, Fredrik; Jansson, John-Olov; Levin, Malin; Borén, Jan; Ohlsson, Claes; Krettek, Alexandra; Romeo, Stefano; Tivesten, Åsa

    2015-01-01

    Androgens have important cardiometabolic actions in males, but their metabolic role in females is unclear. To determine the physiologic androgen receptor (AR)–dependent actions of androgens on atherogenesis in female mice, we generated female AR-knockout (ARKO) mice on an atherosclerosis-prone apolipoprotein E (apoE)–deficient background. After 8 weeks on a high-fat diet, but not on a normal chow diet, atherosclerosis in aorta was increased in ARKO females (+59% vs. control apoE-deficient mice with intact AR gene). They also displayed increased body weight (+18%), body fat percentage (+62%), and hepatic triglyceride levels, reduced insulin sensitivity, and a marked atherogenic dyslipidemia (serum cholesterol, +52%). Differences in atherosclerosis, body weight, and lipid levels between ARKO and control mice were abolished in mice that were ovariectomized before puberty, consistent with a protective action of ovarian androgens mediated via the AR. Furthermore, the AR agonist dihydrotestosterone reduced atherosclerosis (?41%; thoracic aorta), subcutaneous fat mass (?44%), and cholesterol levels (?35%) in ovariectomized mice, reduced hepatocyte lipid accumulation in hepatoma cells in vitro, and regulated mRNA expression of hepatic genes pivotal for lipid homeostasis. In conclusion, we demonstrate that the AR protects against diet-induced atherosclerosis in female mice and propose that this is mediated by modulation of body composition and lipid metabolism.—Fagman, J. B., Wilhelmson, A. S., Motta, B. M., Pirazzi, C., Alexanderson, C., De Gendt, K., Verhoeven, G., Holmäng, A., Anesten, F., Jansson, J.-O., Levin, M., Borén, J., Ohlsson, C., Krettek, A., Romeo, S., Tivesten, A. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice. PMID:25550469

  17. 11?-hydroxysteroid dehydrogenase type 1 deficiency in bone marrow-derived cells reduces atherosclerosis

    PubMed Central

    Kipari, Tiina; Hadoke, Patrick W. F.; Iqbal, Javaid; Man, Tak-Yung; Miller, Eileen; Coutinho, Agnes E.; Zhang, Zhenguang; Sullivan, Katie M.; Mitic, Tijana; Livingstone, Dawn E. W.; Schrecker, Christopher; Samuel, Kay; White, Christopher I.; Bouhlel, M. Amine; Chinetti-Gbaguidi, Giulia; Staels, Bart; Andrew, Ruth; Walker, Brian R.; Savill, John S.; Chapman, Karen E.; Seckl, Jonathan R.

    2013-01-01

    11?-Hydroxysteroid dehydrogenase type-1 (11?-HSD1) converts inert cortisone into active cortisol, amplifying intracellular glucocorticoid action. 11?-HSD1 deficiency improves cardiovascular risk factors in obesity but exacerbates acute inflammation. To determine the effects of 11?-HSD1 deficiency on atherosclerosis and its inflammation, atherosclerosis-prone apolipoprotein E-knockout (ApoE-KO) mice were treated with a selective 11?-HSD1 inhibitor or crossed with 11?-HSD1-KO mice to generate double knockouts (DKOs) and challenged with an atherogenic Western diet. 11?-HSD1 inhibition or deficiency attenuated atherosclerosis (74–76%) without deleterious effects on plaque structure. This occurred without affecting plasma lipids or glucose, suggesting independence from classical metabolic risk factors. KO plaques were not more inflamed and indeed had 36% less T-cell infiltration, associated with 38% reduced circulating monocyte chemoattractant protein-1 (MCP-1) and 36% lower lesional vascular cell adhesion molecule-1 (VCAM-1). Bone marrow (BM) cells are key to the atheroprotection, since transplantation of DKO BM to irradiated ApoE-KO mice reduced atherosclerosis by 51%. 11?-HSD1-null macrophages show 76% enhanced cholesterol ester export. Thus, 11?-HSD1 deficiency reduces atherosclerosis without exaggerated lesional inflammation independent of metabolic risk factors. Selective 11?-HSD1 inhibitors promise novel antiatherosclerosis effects over and above their benefits for metabolic risk factors via effects on BM cells, plausibly macrophages.—Kipari, T., Hadoke, P. W. F., Iqbal, J., Man, T. Y., Miller, E., Coutinho, A. E., Zhang, Z., Sullivan, K. M., Mitic, T., Livingstone, D. E. W., Schrecker, C., Samuel, K., White, C. I., Bouhlel, M. A., Chinetti-Gbaguidi, G., Staels, B., Andrew, R., Walker, B. R., Savill, J. S., Chapman, K. E., Seckl, J. R. 11?-hydroxysteroid dehydrogenase type 1 deficiency in bone marrow-derived cells reduces atherosclerosis. PMID:23303209

  18. Mediterranean diet and carotid atherosclerosis in the Northern Manhattan Study

    PubMed Central

    Gardener, Hannah; Wright, Clinton B.; Cabral, Digna; Scarmeas, Nikolaos; Gu, Yian; Cheung, Ken; Elkind, Mitchell S.V.; Sacco, Ralph L.; Rundek, Tatjana

    2015-01-01

    Objective Adherence to a Mediterranean-style diet (MeDi) may protect against clinical vascular events by reducing atherosclerosis, but data is limited. This is the first observational study of the association between MeDi adherence and carotid plaque thickness and area. Methods The study included 1374 participants of the population-based Northern Manhattan Study with diet assessed and carotid intima-media thickness (cIMT) and plaque measured using B-mode ultrasound (mean age 66 ± 9 years, 60% female, 60% Hispanic, 18% White, 19% Black). A MeDi adherence score (range = 0–9, 9 representing maximal adherence) was examined continuously and in quintiles (3/4/5/6 –9 vs. 0–2). Results Mean cIMT = 0.9 ± 0.1 mm and 57% had plaque (median plaque thickness = 1.5 mm, 75th percentile = 2.2; median plaque area = 4.2 mm2, 75th percentile = 15.8). There was no association between MeDi and cIMT or plaque presence. MeDi adherence was inversely associated with the 75th percentile of plaque thickness and median of plaque area in quantile regression analyses. These associations persisted after controlling for demographics, smoking, physical activity, and total energy consumption (effect of a 1-point increase in MeDi score on the 75th percentile of plaque thickness = ?0.049 mm, p = 0.03; median of plaque area = ?0.371 mm2, p = 0.03), and when additionally controlling for vascular disease biomarkers, medication use, BMI, and previous cardiac disease. The protective associations appeared strongest for those with a MeDi score of 5 (4th quintile) vs. 0–2 (bottom quintile). Differential effects of a MeDi on plaque thickness and area across race/ethnic groups was suggested. Conclusions Moderate and strict adherence to a MeDi may protect against a higher burden of carotid atherosclerotic plaque, which may mediate the protection against clinical vascular events. Efforts to improve adherence to a MeDi are critical to reducing the burden of atherosclerotic disease. PMID:24721190

  19. Track 14. Cardiovascular Mechanics 14.5. Cardiovascular Disease -Atherosclerosis and Aneurysms 1 $289 phase contrast MR demonstrate significant variation in Fontan hemodynamics

    E-print Network

    Frangi, Alejandro

    Track 14. Cardiovascular Mechanics 14.5. Cardiovascular Disease - Atherosclerosis and Aneurysms 1, 08:15-08:45 (P28) Atherosclerosis and aortic aneurysms C.K. Zarins. Stanford University, Stanford, CA. Atherosclerotic enlargement of the human abdom- inal aorta. Atherosclerosis 2001; 155: 164. [2] Draney MT, Arko FR

  20. S100A12 and the S100/Calgranulins: Emerging Biomarkers for Atherosclerosis and Possibly Therapeutic Targets.

    PubMed

    Oesterle, Adam; Hofmann Bowman, Marion A

    2015-12-01

    Atherosclerosis is mediated by local and systematic inflammation. The multiligand receptor for advanced glycation end products (RAGE) has been studied in animals and humans and is an important mediator of inflammation and atherosclerosis. This review focuses on S100/calgranulin proteins (S100A8, S100A9, and S100A12) and their receptor RAGE in mediating vascular inflammation. Mice lack the gene for S100A12, which in humans is located on chromosome 3 between S100A8 and S100A9. Transgenic mice with smooth muscle cell-targeted expression of S100A12 demonstrate increased coronary and aortic calcification, as well as increased plaque vulnerability. Serum S100A12 has recently been shown to predict future cardiovascular events in a longitudinal population study, underscoring a role for S100A12 as a potential biomarker for coronary artery disease. Genetic ablation of S100A9 or RAGE in atherosclerosis-susceptible apolipoprotein E null mice results in reduced atherosclerosis. Importantly, S100A12 and the RAGE axis can be modified pharmacologically. For example, soluble RAGE reduces murine atherosclerosis and vascular inflammation. Additionally, a class of compounds currently in phase III clinical trials for multiple sclerosis and rheumatologic conditions, the quinoline-3-carboxamides, reduce atherosclerotic plaque burden and complexity in transgenic S100A12 apolipoprotein E null mice, but have not been tested with regards to human atherosclerosis. The RAGE axis is an important mediator for inflammation-induced atherosclerosis, and S100A12 has emerged as biomarker for human atherosclerosis. Decreasing inflammation by inhibiting S100/calgranulin-mediated activation of RAGE attenuates murine atherosclerosis, and future studies in patients with coronary artery disease are warranted to confirm S100/RAGE as therapeutic target for atherosclerosis. PMID:26515415

  1. Next generation fire suppressants

    NASA Technical Reports Server (NTRS)

    Brown, Jerry A.

    1995-01-01

    Spectrex, Inc., located in Cedar Grove, NJ is a manufacturer of fire detection and suppression equipment. Spectrex is one of the original pioneers in high speed fire detection and suppression systems for combat vehicles. Spectrex has installed fire suppressions systems in thousands of combat vehicles and ships throughout the world. Additionally, they manufacture flame explosion detectors, ship damage control systems, and optical gas and vapor detectors. The culmination of several years of research and development has recently produced an innovative electro-optical continuous monitoring systems called SharpEye 20/20I IR(sup 3) and SAFEYE that provide fast and reliable gas, vapor, aerosol, flame, and explosion detection. SharpEye 20/20I IR(sup 3) is a self-contained triple spectrum flame detector which scans for oscillating IR radiation (1 to 10 Hz) in the spectral bands ranging from 4.0 to 5.0 microns and uses programmed algorithms to check the ratio and correlation of data received by the three sensors to make the system highly immune to false alarms. It is extremely sensitive as it can detect a 1 x 1 square foot gasoline pan fire at 200 feet in less than 3 seconds. The sensitivity is user programmable, offering 4 ranges of detection. SAFEYE is comprised of a selected number of multispectral ban microprocessors controlled detectors which are in communication with one or more radiation sources that is projected along a 600 feet optical path. The signals from the selected narrow bands are processed and analyzed by highly sophisticated algorithms. It is ideal for high risk, remote, large areas such as petroleum and chemical manufacturing sites, waste dumps, aircraft cargo bays, and ship compartments. The SAFEYE will perform direct readings of the presence or rate of rise of concentrations of gases, vapors, or aerosols at the range of parts per million and provide alarms at various set points at different levels of concentrations.

  2. Atherosclerosis and hypertension induction by lead and cadmium ions: an effect prevented by calcium ion

    SciTech Connect

    Revis, N.W.; Zinsmeistery, A.R.; Bull, R.

    1981-10-01

    In epidemiological studies, both positive and negative correlations have been found between cardiovascular disease and mortality and the presence of several inorganic ions in the drinking water. In an attempt to resolve this apparent disagreement, we exposed White Carneau pigeons to drinking water containing calcium (100 ppm), magnesium (30 ppm), lead (0.8 ppm), or cadmium (0.6 ppm) and used a 2/sup 4/-factorial design to measure the effects of these elements in atherosclerosis and hypertension. The results indicate that (i) lead and cadmium induced aortic atherosclerosis and hypertension, and (ii) calcium protects against the cardiovascular effects of cadmium. Furthermore, the effects were indications that magnesium antagonized the atherosclerotic protective effect of calcium. We suggest that, if these results with the pigeon can be applied to humans, the incidence of aortic atherosclerosis and hypertension should be significantly higher in areas where the drinking water contains magnesium, lead, and cadmium with a relatively low calcium concentration. Furthermore, if hard and soft water produce similar levels of lead and cadmium uptakes, the level of magnesium may be an additional factor in aortic atherosclerosis.

  3. Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis.

    PubMed

    Lobatto, Mark E; Fayad, Zahi A; Silvera, Stephane; Vucic, Esad; Calcagno, Claudia; Mani, Venkatesh; Dickson, Stephen D; Nicolay, Klaas; Banciu, Manuela; Schiffelers, Raymond M; Metselaar, Josbert M; van Bloois, Louis; Wu, Hai-Shan; Fallon, John T; Rudd, James H; Fuster, Valentin; Fisher, Edward A; Storm, Gert; Mulder, Willem J M

    2010-12-01

    Atherosclerosis is an inflammatory disease causing great morbidity and mortality in the Western world. To increase the anti-inflammatory action and decrease adverse effects of glucocorticoids (PLP), a nanomedicinal liposomal formulation of this drug (L-PLP) was developed and intravenously applied at a dose of 15 mg/kg PLP to a rabbit model of atherosclerosis. Since atherosclerosis is a systemic disease, emerging imaging modalities for assessing atherosclerotic plaque are being developed. (18)F-Fluoro-deoxy-glucose positron emission tomography and dynamic contrast enhanced magnetic resonance imaging, methods commonly used in oncology, were applied to longitudinally assess therapeutic efficacy. Significant anti-inflammatory effects were observed as early as 2 days that lasted up to at least 7 days after administration of a single dose of L-PLP. No significant changes were found for the free PLP treated animals. These findings were corroborated by immunohistochemical analysis of macrophage density in the vessel wall. In conclusion, this study evaluates a powerful two-pronged strategy for efficient treatment of atherosclerosis that includes nanomedical therapy of atherosclerotic plaques and the application of noninvasive and clinically approved imaging techniques to monitor delivery and therapeutic responses. Importantly, we demonstrate unprecedented rapid anti-inflammatory effects in atherosclerotic lesions after the nanomedical therapy. PMID:21028895

  4. Bio390 Atherosclerosis and Resistance thanks to Dr. J.F. Anderson,

    E-print Network

    Prestwich, Ken

    . A consequence of atherosclerosis is elevated blood pressure. High blood pressure, in turn, has many undesirable plaque. If the flow of blood is to continue at its usual rate, a higher pressure is required. Estimate the increase in blood pressure required to maintain normal cardiac output when the radii

  5. The macrophage-TCR?? is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis.

    PubMed

    Fuchs, Tina; Puellmann, Kerstin; Emmert, Alexander; Fleig, Julian; Oniga, Septimia; Laird, Rebecca; Heida, Nana Maria; Schäfer, Katrin; Neumaier, Michael; Beham, Alexander W; Kaminski, Wolfgang E

    2015-01-01

    Recent evidence indicates constitutive expression of a recombinatorial TCR?? immune receptor in mammalian monocytes and macrophages. Here, we demonstrate in vitro that macrophage-TCR? repertoires are modulated by atherogenic low density cholesterol (LDL) and high-density cholesterol (HDL). In vivo, analysis of freshly obtained artery specimens from patients with severe carotid atherosclerosis reveals massive abundance of TCR??(+) macrophages within the atherosclerotic lesions. Experimental atherosclerosis in mouse carotids induces accumulation of TCR bearing macrophages in the vascular wall and TCR deficient rag(-/-) mice have an altered macrophage-dependent inflammatory response. We find that the majority of TCR?? bearing macrophages are localized in the hot spot regions of the atherosclerotic lesions. Advanced carotid artery lesions express highly restricted TCR?? repertoires that are characterized by a striking usage of the V?22 and V?16 chains. This together with a significant degree of interindividual lesion repertoire sharing suggests the existence of atherosclerosis-associated TCR?? signatures. Our results implicate the macrophage-TCR?? combinatorial immunoreceptor in atherosclerosis and thus identify an as yet unknown adaptive component in the innate response-to-injury process that underlies this macrophage-driven disease. PMID:25446098

  6. The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis.

    PubMed

    Hovland, Anders; Jonasson, Lena; Garred, Peter; Yndestad, Arne; Aukrust, Pål; Lappegård, Knut T; Espevik, Terje; Mollnes, Tom E

    2015-08-01

    Despite recent medical advances, atherosclerosis is a global burden accounting for numerous deaths and hospital admissions. Immune-mediated inflammation is a major component of the atherosclerotic process, but earlier research focus on adaptive immunity has gradually switched towards the role of innate immunity. The complement system and toll-like receptors (TLRs), and the crosstalk between them, may be of particular interest both with respect to pathogenesis and as therapeutic targets in atherosclerosis. Animal studies indicate that inhibition of C3a and C5a reduces atherosclerosis. In humans modified LDL-cholesterol activate complement and TLRs leading to downstream inflammation, and histopathological studies indicate that the innate immune system is present in atherosclerotic lesions. Moreover, clinical studies have demonstrated that both complement and TLRs are upregulated in atherosclerotic diseases, although interventional trials have this far been disappointing. However, based on recent research showing an intimate interplay between complement and TLRs we propose a model in which combined inhibition of both complement and TLRs may represent a potent anti-inflammatory therapeutic approach to reduce atherosclerosis. PMID:26086357

  7. The Guanine-Nucleotide Exchange Factor SGEF Plays a Crucial Role in the Formation of Atherosclerosis

    PubMed Central

    Kroon, Jeffrey; Welch, Christopher; Bakker, Erik N.; Matlung, Hanke L.; van den Berg, Timo K.; Sharek, Lisa; Doerschuk, Claire; Hahn, Klaus; Burridge, Keith

    2013-01-01

    The passage of leukocytes across the endothelium and into arterial walls is a critical step in the development of atherosclerosis. Previously, we showed in vitro that the RhoG guanine nucleotide exchange factor SGEF (Arhgef26) contributes to the formation of ICAM-1-induced endothelial docking structures that facilitate leukocyte transendothelial migration. To further explore the in vivo role of this protein during inflammation, we generated SGEF-deficient mice. When crossed with ApoE null mice and fed a Western diet, mice lacking SGEF showed a significant decrease in the formation of atherosclerosis in multiple aortic areas. A fluorescent biosensor revealed local activation of RhoG around bead-clustered ICAM-1 in mouse aortic endothelial cells. Notably, this activation was decreased in cells from SGEF-deficient aortas compared to wild type. In addition, scanning electron microscopy of intimal surfaces of SGEF?/? mouse aortas revealed reduced docking structures around beads that were coated with ICAM-1 antibody. Similarly, under conditions of flow, these beads adhered less stably to the luminal surface of carotid arteries from SGEF?/? mice. Taken together, these results show for the first time that a Rho-GEF, namely SGEF, contributes to the formation of atherosclerosis by promoting endothelial docking structures and thereby retention of leukocytes at athero-prone sites of inflammation experiencing high shear flow. SGEF may therefore provide a novel therapeutic target for inhibiting the development of atherosclerosis. PMID:23372835

  8. Agent Based Modeling of Atherosclerosis: A Concrete Help in Personalized Treatments

    NASA Astrophysics Data System (ADS)

    Pappalardo, Francesco; Cincotti, Alessandro; Motta, Alfredo; Pennisi, Marzio

    Atherosclerosis, a pathology affecting arterial blood vessels, is one of most common diseases of the developed countries. We present studies on the increased atherosclerosis risk using an agent based model of atherogenesis that has been previously validated using clinical data. It is well known that the major risk in atherosclerosis is the persistent high level of low density lipoprotein (LDL) concentration. However, it is not known if short period of high LDL concentration can cause irreversible damage and if reduction of the LDL concentration (either by life style or drug) can drastically or partially reduce the already acquired risk. We simulated four different clinical situations in a large set of virtual patients (200 per clinical scenario). In the first one the patients lifestyle maintains the concentration of LDL in a no risk range. This is the control case simulation. The second case is represented by patients having high level of LDL with a delay to apply appropriate treatments; The third scenario is characterized by patients with high LDL levels treated with specific drugs like statins. Finally we simulated patients that are characterized by several oxidative events (smoke, sedentary life style, assumption of alcoholic drinks and so on so forth) that effective increase the risk of LDL oxidation. Those preliminary results obviously need to be clinically investigated. It is clear, however, that SimAthero has the power to concretely help medical doctors and clinicians in choosing personalized treatments for the prevention of the atherosclerosis damages.

  9. Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis.

    PubMed

    Rong, Shunxing; Cao, Qiang; Liu, Mingxia; Seo, Jeongmin; Jia, Lin; Boudyguina, Elena; Gebre, Abraham K; Colvin, Perry L; Smith, Thomas L; Murphy, Robert C; Mishra, Nilamadhab; Parks, John S

    2012-04-01

    12/15 lipoxygenase (12/15LO) oxidizes polyunsaturated fatty acids (PUFAs) to form bioactive lipid mediators. The role of 12/15LO in atherosclerosis development remains controversial. We evaluated atherosclerosis development and lipid metabolism in 12/15LO-LDL receptor (LDLr) double knockout (DK) vs. LDLr knockout (SK) mice fed a PUFA-enriched diet to enhance production of 12/15LO products. Compared with SK controls, DK mice fed a PUFA-enriched diet had decreased plasma and liver lipid levels, hepatic lipogenic gene expression, VLDL secretion, and aortic atherosclerosis and increased VLDL turnover. Bone marrow transplantation and Kupffer cell ablation studies suggested both circulating leukocytes and Kupffer cells contributed to the lipid phenotype in 12/15LO-deficient mice. Conditioned medium from in vitro incubation of DK vs. SK macrophages reduced triglyceride secretion in McArdle 7777 hepatoma cells. Our results suggest that, in the context of dietary PUFA enrichment, macrophage 12/15LO expression adversely affects plasma and hepatic lipid metabolism, resulting in exacerbated atherosclerosis. PMID:22279185

  10. PURINERGIC SIGNALING IN ATHEROSCLEROSIS AND RESTENOSIS Geoffrey Burnstock, Autonomic Neuroscience Centre, Royal Free and University

    E-print Network

    Burnstock, Geoffrey

    secretion, platelet aggregation, mechanosensory transduction, and long-term (trophic) purinergic signaling during changes in blood flow (shear stress) and hypoxia to act on both P2X and P2Y receptors of atherosclerosis and might also regulate the #12;release of a smooth muscle mitogen, platelet-derived growth factor

  11. Acculturation and Subclinical Atherosclerosis among U.S. South Asians: Findings from the MASALA study

    PubMed Central

    Kanaya, AM; Ewing, SK; Vittinghoff, E; Herrington, D; Tegeler, C; Mills, C; Kandula, NR

    2014-01-01

    Objective Longer duration of residence among immigrants to the United States, a proxy measure of acculturation, has been associated with higher subclinical atherosclerosis. South Asian immigrants are the second fastest growing immigrant group in the U.S. but little is known about the effects of acculturation with atherosclerosis in this high cardiovascular risk population. Methods We conducted a cross-sectional analysis using data from a community-based cohort called the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Participants (n=900) were between ages of 40–84 years and had no existing cardiovascular disease. We developed a multi-dimensional measure of acculturation in South Asians, called traditional cultural beliefs, and measured other proxy measures of acculturation to determine whether they were associated with higher levels of subclinical atherosclerosis after controlling for socioeconomic, behavior/lifestyle, and cardiovascular risk factors. Results Mean duration of residence in the U.S. was 27±11 years and tertiles of strength of traditional cultural beliefs were examined. Longer duration of U.S. residence was associated with higher levels of coronary artery calcium even after adjustment for covariates and lifestyle mediators. The novel measure of strength of traditional cultural beliefs was associated with lower common carotid intima media thickness among those with moderate traditional beliefs only. Conclusions These findings support the need for better conceptualization and measurement of how migration influences cultural beliefs and practices, and their subsequent influence on health behaviors and cardiovascular disease risk. PMID:25568891

  12. Sociodemographic correlates of cognition in the multi-ethnic study of atherosclerosis (MESA)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objective was to describe the methodology utilized to evaluate cognitive function in the Multi-Ethnic Study of Atherosclerosis (MESA) and to present preliminary results by age, sex, and race/ethnicity. Cross-sectional measurements of a prospective observational cohort. Residents of 6 U.S. commun...

  13. The influence of glucocorticoids on lipid and lipoprotein metabolism and atherosclerosis.

    PubMed

    Ross, Ian L; Marais, A David

    2014-10-01

    Glucocorticoids have multiple therapeutic uses, but their impact on lipid metabolism and cardiovascular disease risk is not always considered during long-term treatment. Genetic variations, environmental factors and the reasons for glucocorticoid treatment all influence the lipid profile and atherosclerosis. Responses to glucocorticoid treatment may therefore be variable and unpredictable. Despite the frequency with which pharmacological doses of glucocorticoids are used, surprisingly few publications examine their effects on lipid metabolism and atherosclerosis. Patients managed with glucocorticoids should have their cardiovascular risk assessed, especially if long-term treatment is planned. While some apparent favourable changes have been reported in high-density lipoprotein metabolism, very-low-density lipoprotein and low-density lipoprotein responses seem unfavourable. The impact of glucocorticoids on atherosclerosis, which is often viewed as an inflammatory process, is unclear. Glucocorticoid treatment should be undertaken for appropriate indications, but in some instances special attention should be given to management of dyslipidaemia, as long-term survivors of treatment are likely to encounter atherosclerosis. PMID:25363050

  14. GENETIC VARIATION AND DECREASED RISK FOR OBESITY IN THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objective was to investigate the effects of variation in the leptin [LEP (19A>G)] and melanocortin-4 receptor [MC4R (V103I)] genes on obesity-related traits in 13 405 African-American (AA) and white participants from the Atherosclerosis Risk in Communities (ARIC) Study. We tested the association...

  15. Inhibition of Soluble Epoxide Hydrolase in mice promotes reverse cholesterol transport and regression of atherosclerosis

    E-print Network

    Hammock, Bruce D.

    in mice promotes reverse cholesterol transport and regression of atherosclerosis Supplemental Methods: S1LDL) and 5 Ci/mL 3 H-cholesterol for 24 hours. Cells were washed, equilibrated, centrifuged and resuspended in DMEM before intraperitoneal injection. The 3 H-cholesterol levels in macrophages were recorded

  16. Impaired A? clearance: a potential link between atherosclerosis and Alzheimer’s disease

    PubMed Central

    Gupta, Ajay; Iadecola, Costantino

    2015-01-01

    Alzheimer’s Disease (AD) and atherosclerosis remain two of the largest public health burdens in the world today. Although traditionally considered distinct pathological entities, mounting epidemiologic, clinical and experimental evidence suggests that cerebrovascular atherosclerosis and AD interact reciprocally to disrupt brain structure and function. Whereas the hypoperfusion and hypoxia caused by atherosclerosis of cerebral vessels may enhance the production of amyloid-? peptide (A?), a peptide central to AD pathology, A?, in turn, may promote formation of atherosclerotic lesions through vascular oxidative stress and endothelial dysfunction leading to additional vascular damage. Here, we briefly review evidence suggesting that impaired clearance of A? is an additional, simultaneously occurring mechanism by which AD and cerebrovascular disease may be causally linked. We examine the literature supporting mechanisms by which flow-limiting large-artery stenosis, arterial stiffening and microvascular dysfunction could contribute to AD pathophysiology by impairing A? clearance and elevating brain levels of A?. Finally, we highlight the need for further research to improve our understanding of the complex interactions of AD and atherosclerosis with A? clearance, which may ultimately serve to guide the development of novel diagnostic and therapeutic approaches for this devastating and highly prevalent condition. PMID:26136682

  17. Apolipoprotein E gene polymorphisms and retinal vascular signs: The Atherosclerosis Risk in Communities (ARIC) Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objective was to examine the association between apolipoprotein E (APOE) gene polymorphisms and retinal microvascular signs. We used a population-based, cross-sectional study. Participants from the Atherosclerosis Risk in Communities Study (n=10,036; aged 49-73 years) had retinal photographs tak...

  18. CYCLOOXYGENASE POLYMORPHISMS AND RISK OF CARDIOVASCULAR EVENTS: THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cyclooxygenase-derived prostaglandins modulate cardiovascular disease risk. We genotyped 2212 Atherosclerosis Risk in Communities study participants (1,023 incident coronary heart disease (CHD) cases; 270 incident ischemic stroke cases; 919 non-cases) with available DNA for polymorphisms in PTGS1 an...

  19. Despite antiatherogenic metabolic characteristics, SCD1-deficient mice have increased inflammation and atherosclerosis

    PubMed Central

    MacDonald, Marcia L.E.; van Eck, Miranda; Hildebrand, Reeni B.; Wong, Brian W. C.; Bissada, Nagat; Ruddle, Piers; Kontush, Anatol; Hussein, Hala; Pouladi, Mahmoud A.; Chapman, M. John; Fievet, Catherine; van Berkel, Theo J.C.; Staels, Bart; McManus, Bruce M.; Hayden, Michael R.

    2010-01-01

    Objective Absence of stearoyl-CoA desaturase-1 (SCD1) in mice reduces plasma triglycerides and provides protection from obesity and insulin resistance, which would be predicted to be associated with reduced susceptibility to atherosclerosis. The aim of this study was to determine the effect of SCD1 deficiency on atherosclerosis. Methods and Results Despite an antiatherogenic metabolic profile, SCD1 deficiency increases atherosclerosis in hyperlipidemic low density lipoprotein receptor (LDLR)-deficient mice challenged with a western diet. Lesion area at the aortic root is significantly increased in males and females in two models of SCD1 deficiency. Inflammatory changes are evident in the skin of these mice, including increased intercellular adhesion molecule (ICAM)-1 and ulcerative dermatitis. Increases in ICAM-1 and interleukin-6 are also evident in plasma of SCD1-deficient mice. HDL particles demonstrate changes associated with inflammation, including, decreased plasma apoA-II and apoA-I and paraoxonase-1 and increased plasma serum amyloid A. Lipopolysaccharide-induced inflammatory response and cholesterol efflux are not altered in SCD1-deficient macrophages. In addition, when SCD1 deficiency is limited to bone-marrow derived cells, lesion size is not altered in LDLR-deficient mice. Conclusions These studies reinforce the crucial role of chronic inflammation in promoting atherosclerosis, even in the presence of antiatherogenic biochemical and metabolic characteristics. PMID:19095997

  20. LONG-TERM VITAMIN E SUPPLEMENTATION REDUCES ATHEROSCLEROSIS AND MORTALITY IN LDLR-/-MICE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological and experimental evidence indicated potential health benefits of vitamin E supplementation (+E) on coronary heart disease (CHD), but recent clinical trials reported no effect. We hypothesized that +E from early age may prevent or retard development and progression of atherosclerosis...

  1. Blueberry diet protect against atherosclerosis in apoE-deficient mice by inhibiting scavenger receptor expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Atherosclerosis is an inflammatory process that leads to the onset of cardiovascular disease. The scavenger receptor-mediated uptake of oxLDL by macrophages leads to foam cell formation, which is an initial event in the formation of atherosclerotic fatty streak lesions. In this report, the mechanism...

  2. APOLIPOPROTEIN E GENOTYPE AND INCIDENT ISCHEMIC STROKE: THE ATHEROSCLEROSIS RISK IN COMMUNITY STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND AND PURPOSE: A relationship between the apolipoprotein E (apoE) genotype and ischemic stroke has been inconsistently reported. We explored this relation in the Atherosclerosis Risk in Communities Study (ARIC). METHODS: The ARIC cohort involves 15,792 men and women, aged 45 to 64 years at ...

  3. Dietary blueberries sttenuate atherosclerosis in apolipoprotein E-deficient mice by upregulating antioxidant enzymes expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blueberries (BB) contain high levels of polyphenols and exhibit high antioxidant capacity. In this study, protective effects of BB against atherosclerosis and possible underlying mechanisms in reducing oxidative stress were examined in ApoE deficient (apoE-/-) mice. ApoE-/- mice were fed AIN-93G die...

  4. Appropriateness of the hamster as a model to study diet-induced atherosclerosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apo...

  5. Deletion of the phosphoinositide 3-Kinase p110(gamma) gene attenuates murine atherosclerosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inflammatory cell activation by chemokines requires intracellular signaling through phosphoinositide 3-kinase (PI3-kinase) and the PI3-kinase-dependent protein serine/threonine kinase Akt. Atherosclerosis is a chronic inflammatory process driven by oxidatively modified (atherogenic) lipoproteins, ch...

  6. Dietary rice protein isolate attenuates atherosclerosis in apoE-deficient mice by upregulating antioxidant enzymes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice-based diets may have been reported to protect against the development of atherosclerosis; however, the underlying mechanism(s) for this protection remains unknown. In this report, the mechanism(s) contributing to the atheroprotective effects of rice-based diet was addressed using the apolipopro...

  7. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains

    PubMed Central

    Bennett, Brian J.; Davis, Richard C.; Civelek, Mete; Orozco, Luz; Wu, Judy; Qi, Hannah; Pan, Calvin; Packard, René R. Sevag; Eskin, Eleazar; Yan, Mujing; Kirchgessner, Todd; Wang, Zeneng; Li, Xinmin; Gregory, Jill C.; Hazen, Stanley L.; Gargalovic, Peter S.; Lusis, Aldons J.

    2015-01-01

    Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression showed that the combined variations in plasma metabolites, including LDL/VLDL-cholesterol, trimethylamine N-oxide (TMAO), arginine, glucose and insulin, account for approximately 30 to 40% of the variation in atherosclerotic lesion area. Overall, our data provide a rich resource for studies of complex interactions underlying atherosclerosis. PMID:26694027

  8. Preclinical atherosclerosis and metabolic syndrome increase cardio- and cerebrovascular events rate: a 20-year follow up

    PubMed Central

    2013-01-01

    Background Intima-media thickness (IMT) is a validated marker of preclinical atherosclerosis and a predictor of cardiovascular events. Patients We studied a population of 529 asymptomatic patients (age 62?±?12.8 years), divided into two groups of subjects with and without Metabolic Syndrome (MetS). Methods All patients, at baseline, have had a carotid ultrasound evaluation and classified in two subgroups: the first one without atherosclerotic lesions and the second one with preclinical atherosclerosis (increased IMT or asymptomatic carotid plaque). Cardiovascular endpoints were investigated in a 20-years follow-up. Results There were 242 cardiovascular events: 144 among patients with MetS and 98 among in healthy controls (57.4% vs. 35.2%; P?atherosclerosis (31.8% vs. 54.1%; P?atherosclerosis (45% vs. 63.15%; P?=?0.009). 98 events occurred in patients without MetS, of which 27 in the subgroup with normal carotid arteries and 71 in the subgroup with preclinical atherosclerosis (22.88% vs. 44.37%; P?=?0.0003). In addition, considering the 63 total events occurred in patients without atherosclerotic lesions, 36 events were recorded in the subgroup with MetS and 27 events in the subgroup without MetS (45% vs. 22.88%; P?=?0.0019). Finally, in 179 total events recorded in patients with preclinical carotid atherosclerosis, 108 happened in the subgroup with MetS and 71 happened in the subgroup without MetS (63.15% vs. 44.37%; P?=?0.0009). The Kaplan-Meier function showed an improved survival in patients without atherosclerotic lesions compared with patients with carotid ultrasound alterations (P?=?0.01, HR: 0.7366, CI: 0.5479 to 0.9904). Conclusions Preclinical atherosclerosis leads to an increased risk of cardiovascular events, especially if it is associated with MetS. PMID:24152423

  9. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains.

    PubMed

    Bennett, Brian J; Davis, Richard C; Civelek, Mete; Orozco, Luz; Wu, Judy; Qi, Hannah; Pan, Calvin; Packard, René R Sevag; Eskin, Eleazar; Yan, Mujing; Kirchgessner, Todd; Wang, Zeneng; Li, Xinmin; Gregory, Jill C; Hazen, Stanley L; Gargalovic, Peter S; Lusis, Aldons J

    2015-12-01

    Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression showed that the combined variations in plasma metabolites, including LDL/VLDL-cholesterol, trimethylamine N-oxide (TMAO), arginine, glucose and insulin, account for approximately 30 to 40% of the variation in atherosclerotic lesion area. Overall, our data provide a rich resource for studies of complex interactions underlying atherosclerosis. PMID:26694027

  10. Factors influencing dust suppressant effectiveness

    SciTech Connect

    Copeland, C.R.; Eisele, T.C.; Chesney, D.J.; Kawatra, S.K.

    2008-11-15

    Water sprays are a common method used to reduce particulate matter (PM) emissions. Various factors such as wettability, surface area coverage, fine particle engulfment rates, interparticle adhesion forces, suppressant penetration and suppressant longevity have all been suggested as critical factors in achieving effective PM control. However, it has not been established which of these factors are the most important. Experimental work indicated that suppressant penetration is the most critical of these factors. The length of time after application that suppressants were effective was also improved by using hygroscopic reagents that retained moisture to prevent evaporation. Maximizing suppressant penetration and improving suppressant longevity led to an average 86% reduction in PM10 concentrations in laboratory dust tower tests.

  11. The interface of inflammation and subclinical atherosclerosis in granulomatosis with polyangiitis (Wegener's): a preliminary study.

    PubMed

    Hajj-Ali, Rula A; Major, Jennifer; Langford, Carol; Hoffman, Garry S; Clark, Tiffany; Zhang, Li; Sun, Zhiyuan; Silverstein, Roy L

    2015-10-01

    The objective of this study is to assess the relationship between inflammatory disease in granulomatosis with polyangiitis (GPA, Wegener's) and the development of subclinical atherosclerosis. A total of 46 adult patients with GPA were enrolled. Disease status was measured by Birmingham vasculitis assessment scores as modified for GPA, vasculitis damage index, disease duration, and number of relapses. Classic atherosclerotic risk factors, platelet aggregation responses, and circulating microparticle (MP) levels were recorded. All patients underwent carotid artery intima-media thickness (IMT) measurement as outcome for subclinical atherosclerosis. In univariate analyses, systolic and diastolic blood pressure, creatinine, and age were significantly associated with higher IMT (? values 0.37, 0.38, 0.35, and 0.054, respectively [P < 0.02 for all]). In a multiple regression model, greater number of relapses, older age at the onset of disease, and higher diastolic blood pressure were found to be associated with higher IMT (P values 0.003, <0.001, and 0.031, respectively). MP counts and platelet reactivity correlated well with disease activity in GPA. Furthermore, MPs were found to activate vascular endothelial cells and platelets in vitro. The cumulative burden of systemic inflammation in GPA correlated with the development of subclinical atherosclerosis. The correlation with subclinical atherosclerosis could be because of glucocorticoid use and not the inflammatory process in GPA, giving the inherent bias that exits with the use of glucocorticoid with each relapse. The findings of increased levels of circulating leukocyte-derived MPs and enhanced platelet reactivity during relapse suggest possible roles for MPs and platelets in disease pathogenesis and support a growing literature that links inflammation, atherosclerosis, and platelet activation. This hypothesis is further substantiated by our demonstration that MPs isolated from plasma of GPA patients can activate platelets and vascular endothelial cells. PMID:26024800

  12. A CYP26B1 Polymorphism Enhances Retinoic Acid Catabolism and May Aggravate Atherosclerosis

    PubMed Central

    Krivospitskaya, Olesya; Elmabsout, Ali Ateia; Sundman, Eva; Söderström, Leif Å; Ovchinnikova, Olga; Gidlöf, Andreas C; Scherbak, Nikolai; Norata, Giuseppe Danilo; Samnegård, Ann; Törmä, Hans; Abdel-Halim, Samy M; Jansson, Jan-Håkan; Eriksson, Per; Sirsjö, Allan; Olofsson, Peder S

    2012-01-01

    All-trans retinoic acid, controlled by cytochrome P450, family 26 (CYP26) enzymes, potentially has beneficial effects in atherosclerosis treatment. This study investigates CYP26 subfamily B, polypeptide 1 (CYP26B1) in atherosclerosis and the effects of a genetic polymorphism in CYP26B1 on retinoid catabolism. We found that CYP26B1 mRNA was induced by retinoic acid in human atherosclerotic arteries, and CYP26B1 and the macrophage marker CD68 were colocalized in human atherosclerotic lesions. In mice, Cyp26B1 mRNA was higher in atherosclerotic arteries than in normal arteries. Databases were queried for nonsynonymous CYP26B1 single nucleotide polymorphisms (SNPs) and rs2241057 selected for further studies. Constructs of the CYP26B1 variants were created and used for production of purified proteins and transfection of macrophagelike cells. The minor variant catabolized retinoic acid with significantly higher efficiency, indicating that rs2241057 is functional and suggesting reduced retinoid availability in tissues with the minor variant. rs2241057 was investigated in a Stockholm Coronary Atherosclerosis Risk Factor (SCARF) subgroup. The minor allele was associated with slightly larger lesions, as determined by angiography. In summary, this study identifies the first CYP26B1 polymorphism that alters CYP26B1 capacity to metabolize retinoic acid. CYP26B1 was expressed in macrophage-rich areas of human atherosclerotic lesions, induced by retinoic acid and increased in murine atherosclerosis. Taken together, the results indicate that CYP26B1 capacity is genetically regulated and suggest that local CYP26B1 activity may influence atherosclerosis. PMID:22415012

  13. Effect of chondroitin sulphate in a rabbit model of atherosclerosis aggravated by chronic arthritis

    PubMed Central

    Herrero-Beaumont, G; Marcos, M E; Sánchez-Pernaute, O; Granados, R; Ortega, L; Montell, E; Vergés, J; Egido, J; Largo, R

    2008-01-01

    Background and purpose: Among the agents employed to manage osteoarthritis, chondroitin sulphate (CS) is a natural glycosaminoglycan with an anti-inflammatory effect on joint cells. CS might also influence the inflammatory component of atherosclerosis. Our aim was to examine the effect of CS administration on vascular injury and on markers of systemic inflammation in a rabbit model of atherosclerosis aggravated by systemic inflammation provoked by chronic antigen-induced arthritis. Experimental approach: Atherosclerosis was induced in rabbits by maintaining them on a hyperlipidaemic diet after producing an endothelial lesion in the femoral arteries. Simultaneously, chronic arthritis was induced in these animals by repeated intraarticular injections of ovalbumin in previously immunized rabbits. A group of these rabbits were treated prophylactically with CS (100?mg?kg?1day?1) and when the animals were killed, serum and peripheral blood mononuclear cells (PBMC) were isolated. Furthermore, femoral arteries and thoracic aorta were used for gene expression studies and histological examination. Key results: CS administration reduced the concentration of the proinflammatory molecules C-reactive protein and IL-6 in serum. Likewise, CS inhibited the expression of CCL2/monocyte chemoattractant protein (MCP)-1 and cyclooxygenase (COX)-2 in PBMC, and reduced the nuclear translocation of nuclear factor-?B. In the femoral lesion, CS also diminished the expression of CCL2 and COX-2, as well as the ratio of the intima/media thickness. Moreover, CS decreased the percentage of rabbits with atherosclerosis and chronic arthritis that developed vascular lesions in the aorta. Conclusions and implications: These findings suggest that CS treatment may to some extent impede the progression of atherosclerosis. PMID:18536737

  14. Potential role of proteasome on c-jun related signaling in hypercholesterolemia induced atherosclerosis

    PubMed Central

    Sozen, Erdi; Karademir, Betul; Yazgan, Burak; Bozaykut, Perinur; Ozer, Nesrin Kartal

    2014-01-01

    Atherosclerosis and its complications are major causes of death all over the world. One of the major risks of atherosclerosis is hypercholesterolemia. During atherosclerosis, oxidized low density lipoprotein (oxLDL) regulates CD36-mediated activation of c-jun amino terminal kinase-1 (JNK1) and modulates matrix metalloproteinase (MMP) induction which stimulates inflammation with an invasion of monocytes. Additionally, inhibition of proteasome leads to an accumulation of c-jun and phosphorylated c-jun and activation of activator protein-1 (AP-1) related increase of MMP expression. We have previously reported a significant increase in cluster of differentiation 36 (CD36) mRNA levels in hypercholesterolemic rabbits and shown that vitamin E treatment prevented the cholesterol induced increase in CD36 mRNA expression. In the present study, our aim is to identify the signaling molecules/transcription factors involved in the progression of atherosclerosis following CD36 activation in an in vivo model of hypercholesterolemic (induced by 2% cholesterol containing diet) rabbits. In this direction, proteasomal activities by fluorometry and c-jun, phospo c-jun, JNK1, MMP-9 expressions by quantitative RT-PCR and immunoblotting were tested in aortic tissues. The effects of vitamin E on these changes were also investigated in this model. As a result, c-jun was phosphorylated following decreased proteasomal degradation in hypercholesterolemic group. MMP-9 expression was also increased in cholesterol group rabbits contributing to the development of atherosclerosis. In addition, vitamin E showed its effect by decreasing MMP-9 levels and phosphorylation of c-jun. PMID:25009774

  15. Osteoprotegerin is Associated With Endothelial Function and Predicts Early Carotid Atherosclerosis in Patients With Coronary Artery Disease.

    PubMed

    Morisawa, Taichirou; Nakagomi, Akihiro; Kohashi, Keiichi; Kosugi, Munenori; Kusama, Yoshiki; Atarashi, Hirotsugu; Shimizu, Wataru

    2015-12-01

    Osteoprotegerin (OPG) is a soluble glycoprotein belonging to the tumor necrosis factor receptor superfamily and is linked to vascular atherosclerosis and calcification. The carotid intima-media thickness (CIMT) correlates with carotid atherosclerosis and is a significant predictor of cardiovascular events. The OPG levels are associated with the CIMT in coronary artery disease (CAD) patients. However, the pathophysiological mechanisms underlying this pathway remain unclear. We investigated 114 CAD patients (89 men, 25 women; mean age: 68.7 ± 10.3 years) and measured the Gensini score (a marker of the extent of coronary atherosclerosis), the mean CIMT and the plasma levels of OPG and asymmetric dimethylarginine (ADMA; a marker of endothelial function). Early carotid atherosclerosis was defined as a mean CIMT > 1.0 mm. Only 33 of the 114 patients (28.9%) had early carotid atherosclerosis. Patients with early carotid atherosclerosis had higher OPG levels than those without. The OPG levels were found to be significantly associated with ADMA (r = 0.191, P = 0.046) and the mean CIMT (r = 0.319, P = 0.001), but not with the Gensini score. A receiver operating curve analysis revealed the optimal cut-off value of the OPG levels for predicting early carotid atherosclerosis to be 100 pmol/L. A multivariate logistic regression analysis showed OPG ? 100 pmol/L to be significantly and independently associated with early carotid atherosclerosis (odds ratio: 2.98, 95% confidence interval: 1.22-7.20, P = 0.017). These data indicate that OPG is significantly associated with endothelial function and predicts early carotid atherosclerosis in patients with CAD. PMID:26549398

  16. Risk of carotid atherosclerosis associated with genetic polymorphisms of apolipoprotein E and inflammatory genes among arsenic exposed residents in Taiwan

    SciTech Connect

    Hsieh, Y.-C.; Hsieh, F.-I; Lien, L.-M.; Chou, Y.-L.; Chiou, H.-Y. Chen, C.-J.

    2008-02-15

    Arsenic had been reported to be associated with carotid atherosclerosis. However, there were few studies to evaluate the association between the susceptible gene of lipid metabolism and inflammation and carotid atherosclerosis among arsenic exposure residents. The aim of the study was to investigate the associations between the genetic polymorphisms of APOE and MCP-1 and the risk of carotid atherosclerosis among residents of Lanyang Basin in Taiwan which was a newly confirmed arsenic-endemic area. In total, 479 residents who had been genotyped of these two genes and examined the severity of carotid atherosclerosis were included in this study. The study subjects with carotid intima media thickness (IMT) {>=} 1.0 mm or with the observable plaque in the extracranial carotid artery were diagnosed as carotid atherosclerosis. A significantly age- and gender-adjusted odds ratio of 2.0 for the development of carotid atherosclerosis was observed in study subjects with {epsilon}4 allele of APOE than those without {epsilon}4 allele. Compared with study subjects who carried wild genotypes of APOE and MCP-1, those with both risk genotypes of APOE and MCP-1 had 2.5-fold risk of carotid atherosclerosis after adjustment for age and gender, revealing a significant dose-response relationship between number of risk genotypes of these genes and risk of carotid atherosclerosis. Additionally, study subjects with two risk genotypes of APOE and MCP-1 and either had ingested well water contained arsenic level > 10 {mu}g/L or had arsenic exposure > 0.22 mg/L-year would have strikingly highest risk of 10.3-fold and 15.7-fold, respectively, for the development carotid atherosclerosis, showing significant joint effect of arsenic exposure and risk genotypes of APOE and MCP-1.

  17. Pressure suppression system

    DOEpatents

    Gluntz, D.M.

    1994-10-04

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein. 3 figs.

  18. Pressure suppression system

    DOEpatents

    Gluntz, Douglas M. (San Jose, CA)

    1994-01-01

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein.

  19. An Alternative to Thought Suppression?

    ERIC Educational Resources Information Center

    Boice, Robert

    2012-01-01

    Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

  20. STRV Cryocooler Tip Motion Suppression

    NASA Technical Reports Server (NTRS)

    Glaser, R.; Ross, R. G., Jr.; Johnson, D. L.

    1994-01-01

    The Space Technology Research Vehicle (STRV-1b) scheduled to fly at the beginning of June 1994, has a cryocooler vibration suppression experiment aboard doing motion suppression of the tip of the coldfinger. STRV-1b is a bread box sized satellite to be launched on the next flight of the Ariane-4.

  1. Understanding Premature Atherosclerosis in Pediatric SLE: Risk Factors of Increased Carotid Intima Medial Thickness (CIMT) in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Cohort

    PubMed Central

    Schanberg, Laura E.; Sandborg, Christy; Barnhart, Huiman X.; Ardoin, Stacy P.; Yow, Eric; Evans, Gregory W.; Mieszkalski, Kelly L.; Ilowite, Norman T.; Eberhard, Anne; Levy, Deborah M.; Kimura, Yukiko; von Scheven, Emily; Silverman, Earl; Bowyer, Suzanne L.; Punaro, Lynn; Singer, Nora G.; Sherry, David D.; McCurdy, Deborah; Klein-Gitelman, Marissa; Wallace, Carol; Silver, Richard; Wagner-Weiner, Linda; Higgins, Gloria C.; Brunner, Hermine I.; Jung, Lawrence; Soep, Jennifer B.; Reed, Ann

    2009-01-01

    Objective To evaluate risk factors of sub-clinical atherosclerosis in a pediatric SLE population. Methods A prospective multicenter cohort of 221 patients underwent baseline measurements of carotid intima medial thickening (CIMT) as part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial. SLE disease measures, medications, and traditional risk factors for atherosclerosis were assessed. A standardized protocol was used to assess thickness of the bilateral common carotids and mean maximal IMT of 12 segments. Univariable analysis identified potential associations with CIMT that were examined in multivariable linear regression modeling. Results Based on mean-mean common or mean-max CIMT as the dependent variable, univariable analysis showed significant associations with increased CIMT: increasing age, longer SLE duration, minority status, higher BMI, male sex, increased creatinine clearance, higher Lp(a), proteinuria, azathioprine use, and prednisone dose. Azathioprine use (P=0.005 for mean-mean common; P=0.102 for mean-max model) and male sex (P< 0.001) were both associated with increases in mean-max CIMT. Moderate dose prednisone (0.15–0.4 mg/kg/day) was associated with decreases in mean-max CIMT (P=0.024) while high or low dose prednisone was associated with mean-mean common CIMT (P=0.021) or mean-max CIMT (P=0.064), respectively. BMI (P<0.001) and creatinine clearance (P=0.031), remained associated with increased mean-mean common CIMT, while increasing age (P<0.001) and increasing Lp(a) (P=0.005) were associated with increased mean-max CIMT. Conclusion Traditional as well as non-traditional risk factors are associated with increased CIMT in pediatric SLE patients in this cohort. Azathioprine treatment was associated with increased CIMT. The relationship of CIMT with prednisone dose may not be linear. PMID:19404953

  2. Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis

    PubMed Central

    Chen, Suet Nee; Cilingiroglu, Mehmet; Todd, Josh; Lombardi, Raffaella; Willerson, James T; Gotto, Antonio M; Ballantyne, Christie M; Marian, AJ

    2009-01-01

    Background Plasma level of high-density lipoprotein-cholesterol (HDL-C), a heritable trait, is an important determinant of susceptibility to atherosclerosis. Non-synonymous and regulatory single nucleotide polymorphisms (SNPs) in genes implicated in HDL-C synthesis and metabolism are likely to influence plasma HDL-C, apolipoprotein A-I (apo A-I) levels and severity of coronary atherosclerosis. Methods We genotyped 784 unrelated Caucasian individuals from two sets of populations (Lipoprotein and Coronary Atherosclerosis Study- LCAS, N = 333 and TexGen, N = 451) for 94 SNPs in 42 candidate genes by 5' nuclease assays. We tested the distribution of the phenotypes by the Shapiro-Wilk normality test. We used Box-Cox regression to analyze associations of the non-normally distributed phenotypes (plasma HDL-C and apo A-I levels) with the genotypes. We included sex, age, body mass index (BMI), diabetes mellitus (DM), and cigarette smoking as covariates. We calculated the q values as indicators of the false positive discovery rate (FDR). Results Plasma HDL-C levels were associated with sex (higher in females), BMI (inversely), smoking (lower in smokers), DM (lower in those with DM) and SNPs in APOA5, APOC2, CETP, LPL and LIPC (each q ?0.01). Likewise, plasma apo A-I levels, available in the LCAS subset, were associated with SNPs in CETP, APOA5, and APOC2 as well as with BMI, sex and age (all q values ?0.03). The APOA5 variant S19W was also associated with minimal lumen diameter (MLD) of coronary atherosclerotic lesions, a quantitative index of severity of coronary atherosclerosis (q = 0.018); mean number of coronary artery occlusions (p = 0.034) at the baseline and progression of coronary atherosclerosis, as indicated by the loss of MLD. Conclusion Putatively functional variants of APOA2, APOA5, APOC2, CETP, LPL, LIPC and SOAT2 are independent genetic determinants of plasma HDL-C levels. The non-synonymous S19W SNP in APOA5 is also an independent determinant of plasma apo A-I level, severity of coronary atherosclerosis and its progression. PMID:19878569

  3. Neighborhood health-promoting resources and obesity risk (the Multi-Ethnic Study of Atherosclerosis). — Measures of the Food Environment

    Cancer.gov

    Auchincloss AH, Mujahid MS, Shen M, Michos ED, Whitt-Glover MC, Diez Roux AV. Neighborhood health-promoting resources and obesity risk (the Multi-Ethnic Study of Atherosclerosis). Obesity (Silver Spring) 2012 Apr 19.

  4. Lipid Metabolism, Learning Ability and Potential Biomarkers for Atherosclerosis in Monk Parrots (Myiopsitta monachus) Fed N-3 Fatty Acids 

    E-print Network

    Petzinger, Christina

    2012-07-16

    associated with the development of atherosclerosis in mammals. N-3 polyunsaturated fatty acids (PUFA) have also been linked to improving retinal, neurological, and brain development and functioning. In order to assess the effects of n-3 PUFA on potential risk...

  5. Algorithms for Fluorescence Lifetime Microscopy and Optical Coherence Tomography Data Analysis: Applications for Diagnosis of Atherosclerosis and Oral Cancer 

    E-print Network

    Pande, Paritosh

    2014-05-16

    imaging (FLIM) with optical coherence tomography (OCT), for the diagnosis of atherosclerosis and oral cancer. FLIM is a fluorescence imaging technique that is capable of providing information about auto fluorescent tissue biomolecules. OCT on the other...

  6. Identification of candidate genes linking systemic inflammation to atherosclerosis; results of a human in vivo LPS infusion study.

    E-print Network

    Sivapalaratnam, Suthesh; Farrugia, Rosienne; Nieuwdorp, Max; Langford, Cordelia F.; Van Beem, Rachel T.; Maiwald, Stephanie; Zwaginga, Jaap Jan; Gusnanto, Arief; Watkins, Nicholas A.; Trip, Mieke D.; Ouwehand, Willem H.

    2011-08-10

    Abstract Background It is widely accepted that atherosclerosis and inflammation are intimately linked. Monocytes play a key role in both of these processes and we hypothesized that activation of inflammatory pathways in monocytes would lead to...

  7. Clinical significance of subclinical carotid atherosclerosis and its relationship with echocardiographic parameters in non-diabetic chronic kidney disease patients

    PubMed Central

    2013-01-01

    Background Non-diabetic chronic kidney disease (CKD) patients are a heterogeneous group with a variety of prognosis. We investigated the role of subclinical carotid atherosclerosis for the prediction of adverse cardiovascular (CV) outcomes in these patients, and tried to identify clinical and echocardiographic parameters associated with subclinical carotid atherosclerosis. Methods As a prospective design, 182 asymptomatic non-diabetic CKD patients underwent carotid ultrasonography and Doppler echocardiography. Carotid atherosclerosis was defined as a carotid intima-media thickness ?1.0 mm and/or the presence of plaque. Results During the mean follow-up period of 28.8?±?16.1 months, 23 adverse CV events occurred. Patients with carotid atherosclerosis (99, 54.4%) showed significantly higher rates of annual CV events than those without (8.6 vs. 1.5%, p <0.001). Particularly, the presence of carotid plaque was a powerful predictor of adverse CV outcomes (OR 7.80, 95% CI 1.45-45.97). Clinical parameters associated with the presence of subclinical carotid atherosclerosis were old age, previous history of hypertension, increased pulse pressure, and higher high-sensitivity C-reactive protein (hs-CRP) level. By echocardiography, early diastolic mitral annular velocity (E’) and the ratio of early peak transmitral inflow velocity (E) to E’ (E/E’) were closely related with the presence of carotid atherosclerosis. A multivariate analysis showed that age, hs-CRP, and E/E’ were significant determinants of carotid atherosclerosis. Conclusions Carotid plaque, even subclinical, was closely associated with a poor prognosis in non-diabetic CKD patients. Increased age, hs-CRP level, and E/E’ ratio may be useful markers suggesting the presence of carotid atherosclerosis in these patients. PMID:24192205

  8. Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis

    SciTech Connect

    Wu, M.-M.; Chiou, H.-Y. . E-mail: hychiou@tmu.edu.tw; Hsueh, Y.-M.; Hong, C.-T.; Su, C.-L.; Chang, S.-F.; Huang, W.-L.; Wang, H.-T.; Wang, Y.-H.; Hsieh, Y.-C.; Chen, C.-J.

    2006-10-01

    Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA{sup V}) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA{sup V} (MMA%) was calculated by dividing with total arsenic species in urine, including arsenite, arsenate, MMA{sup V}, and dimethylarsinic acid (DMA{sup V}). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of arsenic exposure on the risk of atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma homocysteine levels did not confer an independent risk for developing atherosclerosis in the study population. However, the risk of having atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% ({>=}16.5%) and high homocysteine levels ({>=}12.7 {mu}mol/l) as compared to those with low MMA% (<9.9%) and low homocysteine levels (<12.7 {mu}mol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine.

  9. CD36-Dependent 7-Ketocholesterol Accumulation in Macrophages Mediates Progression of Atherosclerosis in Response to Chronic Air Pollution Exposure

    PubMed Central

    Maiseyeu, Andrei; Gopalakrishnan, Bhavani; Villamena, Frederick A.; Chen, Lung-Chi; Harkema, Jack R; Sun, Qinghua; Rajagopalan, Sanjay

    2014-01-01

    Rationale Air pollution exposure has been shown to potentiate plaque progression in humans and animals. Our previous studies have suggested a role for oxidized lipids in mediating adverse vascular effect of air pollution. However, the types of oxidized lipids formed in response to air pollutants and how this occurs and their relevance to atherosclerosis is not fully understood. Objective To investigate the mechanisms by which particulate matter< 2.5?m (PM2.5) induces progression of atherosclerosis. Methods and Results Atherosclerosis-prone ApoE?/? or LDLR?/? mice were exposed to filtered air or concentrated ambient PM2.5 using a versatile aerosol concentrator enrichment system for 6 months. PM2.5 increased 7-ketocholesterol (7-KCh), an oxidatively modified form of cholesterol, in plasma IDL/LDL fraction and in aortic plaque concomitant with progression of atherosclerosis and increased CD36 expression in plaque-macrophages from PM2.5-exposed mice. Macrophages isolated from PM2.5-exposed mice displayed increased uptake of oxidized lipids without alterations in their efflux capacity. Consistent with these finding, CD36-positive macrophages displayed a heightened capacity for oxidized lipid uptake. Deficiency of CD36 on hematopoietic cells diminished the effect of air pollution on 7-KCh accumulation, foam cell formation, and atherosclerosis. Conclusions Our results suggest a potential role for CD36-mediated abnormal accumulations of oxidized lipids such as 7-KCh in air pollution induced atherosclerosis progression. PMID:25186795

  10. Molecular anatomy of ascending aorta in atherosclerosis by MS Imaging: Specific lipid and protein patterns reflect pathology.

    PubMed

    Martin-Lorenzo, Marta; Balluff, Benjamin; Maroto, Aroa S; Carreira, Ricardo J; van Zeijl, Rene J M; Gonzalez-Calero, Laura; de la Cuesta, Fernando; Barderas, Maria G; Lopez-Almodovar, Luis F; Padial, Luis R; McDonnell, Liam A; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2015-08-01

    The molecular anatomy of healthy and atherosclerotic tissue is pursued here to identify ongoing molecular changes in atherosclerosis development. Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. Mass spectrometry imaging (MSI) is a novel unexplored ex vivo imaging approach in CVD able to provide in-tissue molecular maps. A rabbit model of early atherosclerosis was developed and high-spatial-resolution MALDI-MSI was applied to comparatively analyze histologically-based arterial regions of interest from control and early atherosclerotic aortas. Specific protocols were applied to identify lipids and proteins significantly altered in response to atherosclerosis. Observed protein alterations were confirmed by immunohistochemistry in rabbit tissue, and additionally in human aortas. Molecular features specifically defining different arterial regions were identified. Localized in the intima, increased expression of SFA and lysolipids and intimal spatial organization showing accumulation of PI, PG and SM point to endothelial dysfunction and triggered inflammatory response. TG, PA, SM and PE-Cer were identified specifically located in calcified regions. Thymosin ?4 (TMSB4X) protein was upregulated in intima versus media layer and also in response to atherosclerosis. This overexpression and localization was confirmed in human aortas. In conclusion, molecular histology by MS Imaging identifies spatial organization of arterial tissue in response to atherosclerosis. PMID:26079611

  11. Integrated mechanical and structural features for photoacoustic characterization of atherosclerosis using a quasi-continuous laser.

    PubMed

    Chen, Conggui; Zhao, Yue; Yang, Sihua; Xing, Da

    2015-06-29

    We present a novel integrated mechanical and structural photoacoustic imaging (IMS-PAI) for atherosclerosis characterization. A quasi-continuous laser with pulse width of 22 ns and repetition frequency of 25 KHz was used to realize simultaneous acquisition of PA phase and temporal intensity. An algorithm utilizing sound propagation model in conjunction with temporal PA intensity was developed and applied to correct the phase deviation caused by uneven tissue surface. Integration of en-face mechanical and in-depth structural PA imaging was verified by a tissue-mimicking phantom. Moreover, complementary visualization of en-face viscoelasticity distribution and in-depth structural anatomy of an atherosclerotic tissue was achieved, which was consistent with the histology. The results demonstrated the IMS-PAI has an attractive synergy in comprehensive atherosclerosis characterization. PMID:26191740

  12. Intimal pericytes as the second line of immune defence in atherosclerosis

    PubMed Central

    Ivanova, Ekaterina A; Bobryshev, Yuri V; Orekhov, Alexander N

    2015-01-01

    Inflammation plays an essential role in the development of atherosclerosis. The initiation and growth of atherosclerotic plaques is accompanied by recruitment of inflammatory and precursor cells from the bloodstream and their differentiation towards pro-inflammatory phenotypes. This process is orchestrated by the production of a number of pro-inflammatory cytokines and chemokines. Human arterial intima consists of structurally distinct leaflets, with a proteoglycan-rich layer lying immediately below the endothelial lining. Recent studies reveal the important role of stellate pericyte-like cells (intimal pericytes) populating the proteoglycan-rich layer in the development of atherosclerosis. During the pathologic process, intimal pericytes may participate in the recruitment of inflammatory cells by producing signalling molecules and play a role in the antigen presentation. Intimal pericytes are also involved in lipid accumulation and the formation of foam cells. This review focuses on the role of pericyte-like cells in the development of atherosclerotic lesions. PMID:26516412

  13. Design and Rationale for the Study of Changes in Iron and Atherosclerosis Risk in Perimenopause

    PubMed Central

    Mihai, Georgeta; He, Xin; Zhang, Xiaolan; McCarthy, Beth; Tran, Tam; Pennell, Michael; Blank, Jessica; Simonetti, Orlando P.; Jackson, Rebecca D.; Raman, Subha V.

    2012-01-01

    This study seeks to investigate changes in iron homeostasis and carotid arteries in women at risk of atherosclerosis, addressing a relatively unexplored hypothesis explaining why women have a 5-10 year lag in initial atherosclerotic events. Recent evidence points to hepcidin, the key regulator of macrophage iron uptake and release, as a potential mediator of risk. Furthermore, iron catalyzes the generation of free radicals that oxidize cholesterol stimulating atheroma formation. Magnetic resonance imaging (MRI) is ideally suited to study iron because of iron’s local effects on magnetic susceptibility that can be quantified using a relaxation parameter called T2* (‘T2-star’), as well as the ability to noninvasively characterize and quantify atherosclerotic plaque with MRI. This work outlines the rationale and study design to provide critical evidence related to the iron hypothesis, such that novel diagnostics and therapeutics to attenuate risk may be derived from a better understanding of iron’s role in atherosclerosis. PMID:22348199

  14. The identification of the variation of atherosclerosis plaques by invasive and non-invasive methods

    NASA Technical Reports Server (NTRS)

    Selzer, R. H.; Blankenhorn, D. H.

    1982-01-01

    Computer-enhanced visualization of coronary arteries and lesions within them is discussed, comparing invasive and noninvasive methods. Trial design factors in computer lesions assessment are briefly discussed, and the use of the computer edge-tracking technique in that assessment is described. The results of a small pilot study conducted on serial cineangiograms of men with premature atherosclerosis are presented. A canine study to determine the feasibility of quantifying atherosclerosis from intravenous carotid angiograms is discussed. Comparative error for arterial and venous injection in the canines is determined, and the mode of processing the films to achieve better visualization is described. The application of the computer edge-tracking technique to an ultrasound image of the human carotid artery is also shown and briefly discussed.

  15. Aminolevulinic acid with gold nanoparticles: a novel theranostic agent for atherosclerosis.

    PubMed

    de Oliveira Gonçalves, Karina; da Silva, Monica Nascimento; Sicchieri, Letícia Bonfante; de Oliveira Silva, Flávia Rodrigues; de Matos, Ricardo Almeida; Courrol, Lilia Coronato

    2015-03-21

    In this study, 5-aminolevulinic acid (ALA) gold nanoparticles (ALA:AuNPs) functionalized with polyethylene glycol (PEG) were synthesized and administered to rabbits to evaluate their use in clinical practice as theranostic agents for atherosclerosis. This was done by measuring the porphyrin fluorescence extracted from the rabbits' blood and feces. An increase in blood and feces porphyrin emission after ALA:AuNP administration suggests that ALA was incorporated by gold nanoparticles, its structure was preserved, and a rapid conversion into endogenous porphyrins occurred, overloading the synthetic pathway that led to protoporphyrin IX (PPIX) accumulation. This finding indicated that this method can aid in the early diagnosis and therapy of atherosclerosis with high sensitivity. PMID:25671550

  16. Adventitial fibroblasts are activated in the early stages of atherosclerosis in the apolipoprotein E knockout mouse

    SciTech Connect

    Xu Fang; Ji Jian; Li Li; Chen Rong; Hu Weicheng . E-mail: huweicheng@sdu.edu.cn

    2007-01-19

    The role of the adventitia in vascular function and vascular lesion formation has been largely ignored. This study observed the activation of the adventitia and specifically the fibroblasts in the development of atherosclerosis in the apoE(-/-) mouse. The results showed a gradual increase in expression of collagen types I and III after 2, 4, and 8 weeks of hyperlipidic diet. The earliest expression of monocyte chemoattractant protein-1 (MCP-1) protein and mRNA was detected in the adventitial fibroblast before the formation of intimal lesions. Proliferation, too, was first found in the adventitial fibroblasts. We hypothesize that the adventitial fibroblast is activated in the early stage of atherosclerosis. Adventitial inflammation may be an early event in the development of atherosclerotic lesions.

  17. One-pot synthesis of magnetic nanoclusters enabling atherosclerosis-targeted magnetic resonance imaging

    PubMed Central

    Kukreja, Aastha; Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Lee, Taeksu; Suh, Jin-Suck; Huh, Yong-Min; Haam, Seungjoo

    2014-01-01

    In this study, dextran-encrusted magnetic nanoclusters (DMNCs) were synthesized using a one-pot solution phase method for detection of atherosclerosis by magnetic resonance imaging. Pyrenyl dextran was used as a surfactant because of its electron-stabilizing effect and its amphiphilic nature, rendering the DMNCs stable and water-dispersible. The DMNCs were 65.6±4.3 nm, had a narrow size distribution, and were superparamagnetic with a high magnetization value of 60.1 emu/g. Further, they showed biocompatibility and high cellular uptake efficiency, as indicated by a strong interaction between dextran and macrophages. In vivo magnetic resonance imaging demonstrated the ability of DMNCs to act as an efficient magnetic resonance imaging contrast agent capable of targeted detection of atherosclerosis. In view of these findings, it is concluded that DMNCs can be used as magnetic resonance imaging contrast agents to detect inflammatory disease. PMID:24904209

  18. Role of Endoplasmic Reticulum Stress in Atherosclerosis and Diabetic Macrovascular Complications

    PubMed Central

    Chistiakov, Dmitry A.; Sobenin, Igor A.; Orekhov, Alexander N.; Bobryshev, Yuri V.

    2014-01-01

    Age-related changes in endoplasmic reticulum (ER) are associated with stress of this cell organelle. Unfolded protein response (UPR) is a normal physiological reaction of a cell in order to prevent accumulation of unfolded and misfolded proteins in the ER and improve the normal ER function. However, in pathologic conditions such as atherosclerosis, obesity, and diabetes, ER function becomes impaired, leading to the development of ER stress. In chronic ER stress, defective posttranslational protein folding results in deposits of aberrantly folded proteins in the ER and the induction of cell apoptosis mediated by UPR sensors C/EBP?-homologous protein (CHOP) and inositol requiring protein-1 (IRE1). Since ER stress and ER-induced cell death play a nonredundant role in the pathogenesis of atherosclerosis and diabetic macrovascular complications, pharmaceutical targeting of ER stress components and pathways may be beneficial in the treatment and prevention of cardiovascular pathology. PMID:25061609

  19. Chinese Herbal Compounds for the Prevention and Treatment of Atherosclerosis: Experimental Evidence and Mechanisms

    PubMed Central

    Li, Jianping; Hartstone-Rose, Adam; Wang, Jing; Li, Jiqiang; Janicki, Joseph S.

    2015-01-01

    Atherosclerosis is a leading cause of disability and death worldwide. Research into the disease has led to many compelling hypotheses regarding the pathophysiology of atherosclerotic lesion formation and the resulting complications such as myocardial infarction and stroke. Herbal medicine has been widely used in China as well as other Asian countries for the treatment of cardiovascular diseases for hundreds of years; however, the mechanisms of action of Chinese herbal medicine in the prevention and treatment of atherosclerosis have not been well studied. In this review, we briefly describe the mechanisms of atherogenesis and then summarize the research that has been performed in recent years regarding the effectiveness and mechanisms of antiatherogenic Chinese herbal compounds in an attempt to build a bridge between traditional Chinese medicine and cellular and molecular cardiovascular medicine. PMID:26089946

  20. Effects of calcium, magnesium, lead, or cadmium on lipoprotein metabolism and atherosclerosis in the pigeon

    SciTech Connect

    Revis, N.W.; Major, T.C.; Horton, C.Y.

    1980-01-01

    Epidemiological and clincal studies suggest that the incidence of atherosclerosis is higher in soft-water areas than in hard-water areas. In an attempt to discern the factor(s) in drinking water that may be associated with these observations, the current studies were performed to determine the effects of several elements associated with hard (i.e., calcium and magnesium) or soft (i.e., calcium and magnesium) or soft (i.e., cadmium and lead) water in the induction and progression of atherosclerosis in the white carneau pigeon. The effect of these elements on lipoprotein metabolism was also assessed because it has been suggested that changes in the metabolism of lipoprotein may play a role in the etiology of atherosclerosis. Results show that the number and size of atherosclerotic plaques in the aorta were increased in pigeons given drinking water containing lead and/or cadmium. The effects of these elements were antagonized by the addition of calcium to drinking water containing lead and/or cadmium. Although lead and cadmium altered the profile of lipoproteins, this change did not appear to be related to an increase in the number and size of atherosclerotic plaques of the aorta. However, in pigeons treated with calcium alone the low-density lipoprotein (LDL) increased fourfold, and arteriosclerosis of the coronary arteries was observed. This result suggests that marked increases in the LDL protein may be related to arteriosclerosis of the coronary arteries. Based on these preliminary results, we suggest that lead, cadmium, and the LDL protein may be important factors in the induction and progression of atherosclerosis and arteriosclerosis in the pigeon.

  1. Circulating Vitamin D Metabolites and Subclinical Atherosclerosis in Type 1 Diabetes

    PubMed Central

    Sachs, Michael C.; Brunzell, John D.; Cleary, Patricia A.; Hoofnagle, Andrew N.; Lachin, John M.; Molitch, Mark E.; Steffes, Michael W.; Zinman, Bernard; de Boer, Ian H.

    2013-01-01

    OBJECTIVE People with type 1 diabetes are at high risk of premature atherosclerosis. Existing evidence suggests that impaired vitamin D metabolism may contribute to the development of atherosclerosis. We tested associations of circulating vitamin D metabolite concentrations with subclinical atherosclerosis among 1,193 participants with type 1 diabetes in the DCCT/EDIC study. RESEARCH DESIGN AND METHODS We measured plasma concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D by mass spectrometry at the end of the DCCT. In a staggered cross-sectional design, we tested associations with coronary artery calcium (CAC), measured by computed tomography a median of 10 years later, and with common and internal carotid intima-media thickness (IMT), measured by B-mode ultrasonography on two occasions a median of 4 years later and a median of 10 years later. We hypothesized that lower concentrations of each vitamin D metabolite would be associated with increased risk of CAC and greater carotid IMT. RESULTS At the time metabolites were measured, mean age was 32.4 years and mean duration of diabetes was 7.5 years. The prevalence and severity of CAC tended to be lower—not higher—with lower concentrations of each vitamin D metabolite. For instance, in a fully adjusted multinomial logistic model, a 25 nmol/L lower 25-hydroxyvitamin D was associated with a 0.8-fold decrease in the odds of having higher CAC (95% CI 0.68–0.96, P = 0.01). No vitamin D metabolite was associated with either common or internal mean IMT. CONCLUSIONS We did not find evidence linking impaired vitamin D metabolism with increased subclinical atherosclerosis in type 1 diabetes. PMID:23530012

  2. Loss of apoptosis regulator through modulating IAP expression (ARIA) protects blood vessels from atherosclerosis.

    PubMed

    Matsuo, Kiyonari; Akakabe, Yoshiki; Kitamura, Youhei; Shimoda, Yoshiaki; Ono, Kazunori; Ueyama, Tomomi; Matoba, Satoaki; Yamada, Hiroyuki; Hatakeyama, Kinta; Asada, Yujiro; Emoto, Noriaki; Ikeda, Koji

    2015-02-01

    Atherosclerosis is the primary cause for cardiovascular disease. Here we identified a novel mechanism underlying atherosclerosis, which is provided by ARIA (apoptosis regulator through modulating IAP expression), the transmembrane protein that we recently identified. ARIA is expressed in macrophages present in human atherosclerotic plaque as well as in mouse peritoneal macrophages. When challenged with acetylated LDL, peritoneal macrophages isolated from ARIA-deficient mice showed substantially reduced foam cell formation, whereas the uptake did not differ from that in wild-type macrophages. Mechanistically, loss of ARIA enhanced PI3K/Akt signaling and consequently reduced the expression of acyl coenzyme A:cholesterol acyltransferase-1 (ACAT-1), an enzyme that esterifies cholesterol and promotes its storage, in macrophages. Inhibition of PI3K abolished the reduction in ACAT-1 expression and foam cell formation in ARIA-deficient macrophages. In contrast, overexpression of ARIA reduced Akt activity and enhanced foam cell formation in RAW264.7 macrophages, which was abrogated by treatment with ACAT inhibitor. Of note, genetic deletion of ARIA significantly reduced the atherosclerosis in ApoE-deficient mice. Oil red-O-positive lipid-rich lesion was reduced, which was accompanied by an increase of collagen fiber and decrease of necrotic core lesion in atherosclerotic plaque in ARIA/ApoE double-deficient mice. Analysis of bone marrow chimeric mice revealed that loss of ARIA in bone marrow cells was sufficient to reduce the atherosclerogenesis in ApoE-deficient mice. Together, we identified a unique role of ARIA in the pathogenesis of atherosclerosis at least partly by modulating macrophage foam cell formation. Our results indicate that ARIA could serve as a novel pharmacotherapeutic target for the treatment of atherosclerotic diseases. PMID:25533470

  3. Association of Television Viewing Time with Body Composition and Calcified Subclinical Atherosclerosis in Singapore Chinese

    PubMed Central

    Nang, Ei Ei Khaing; van Dam, Rob M.; Tan, Chuen Seng; Mueller-Riemenschneider, Falk; Lim, Yi Ting; Ong, Kai Zhi; Ee, Siqing; Lee, Jeannette; Tai, E. Shyong

    2015-01-01

    Objective Sedentary behavior such as television viewing may be an independent risk factor for coronary heart disease. However, few studies have assessed the impact of television viewing time on coronary artery calcification and it remains unclear how body fat contributes to this relationship. The aim of this study is to evaluate the association between television viewing time and subclinical atherosclerosis and whether effects on visceral or subcutaneous fat may mediate any associations observed. Methods This was a cross-sectional study of 398 Chinese participants (192 men and 206 women) from Singapore prospective study. Participants were free from known cardiovascular diseases and underwent interview, health screening, computed tomography scans of coronary arteries and abdomen. Spearman’s correlation was used to test the correlation between television viewing time, physical activity, body composition and abdominal fat distribution. The association between television viewing time and subclinical atherosclerosis was assessed by multiple logistic regression analysis. Results In men, television viewing time was significantly correlated with higher body fat mass index, percent body fat, subcutaneous and visceral fat. These associations were in the same direction, but weaker and not statistically significant in women. Television viewing time (hours/day) was associated with subclinical atherosclerosis in men (odds ratio: 1.41, 95% CI: 1.03-1.93) but no significant association was observed in women (odds ratio: 0.88, 95% CI: 0.59-1.31) after adjusting for potential socio-demographic and lifestyle confounders. Further adjustments for biological factors did not affect these associations. Conclusions Television viewing time was associated with greater adiposity and higher subcutaneous and visceral fat in men. TV viewing time was also associated with subclinical atherosclerosis in men and the potential mechanisms underlying this association require further investigation. PMID:26132754

  4. Reduced endothelial progenitor cells in European and South Asian men with atherosclerosis

    PubMed Central

    Hughes, A. D.; Coady, E.; Raynor, S.; Mayet, J.; Wright, A. R.; Shore, A. C.; Kooner, J. S.; Thom, S. A. McG.; Chaturvedi, N.

    2007-01-01

    Background Circulating endothelial progenitor cells (EPCs) play a role in the repair and regeneration of the endothelium and may represent a novel cardiovascular risk factor. South Asian subjects have an increased risk of cardiovascular disease which is not fully explained by known risk factors. This study examined associations of EPCs with atherosclerosis and possible ethnic differences in EPCs. Materials and methods A population sample of 58 European and South Asian adult men was enriched with the recruitment of an additional 59 European and South Asian men with known coronary disease. The coronary artery calcification score was measured by multi-slice computerized tomography (CT), carotid and femoral intima-media thickness (IMT), and femoral plaques were measured by ultrasound. The subjects were further subdivided into three categories of coronary artery disease on the basis of coronary artery calcification score and clinical history. Total EPCs and non-senescent EPCs (ns-EPCs) were quantified after 5 days cell culture and the number of late outgrowth colonies was measured over a 6-week test period. Circulating CD34+ haematopoietic precursor cells were measured by flow cytometry. Results Individuals with femoral plaques had reduced total and ns-EPCs. The number of ns-EPCs were reduced in individuals with the most coronary atheroma and were inversely related to the coronary calcification score and femoral IMT. These relationships persisted after multivariate adjustment for other risk factors. The numbers of late outgrowth colonies or circulating CD34+ cells were unrelated to the presence of atherosclerosis. There were no differences in the number of EPCs between European and South Asian subjects. Conclusion The number of EPCs are reduced in subjects with atherosclerosis independent of other risk factors. Reduction in EPC numbers may be an independent risk factor for atherosclerosis but does not explain ethnic differences in cardiovascular risk. PMID:17181565

  5. Enhanced susceptibility of cyclin kinase inhibitor p21 knockout mice to high fat diet induced atherosclerosis

    PubMed Central

    Khanna, Ashwani K

    2009-01-01

    Cyclin kinase inhibitor p21 is one of the most potent inhibitors of aortic smooth muscle cell proliferation, a key mediator of atherosclerosis. This study tests if p2l deficiency will result in severe atherosclerosis in a mouse model. p21-/- and strain matched wild type mice were fed with high fat diet for 21 weeks. Analysis for biochemical parameters (cholesterol, triglycerides) in serum and mRNA expression of CD36, HO-1, TGF-?, IFN-?, TNF-?, PPAR-? and NADPH oxidase components (p22phox, NOX-1 and Rac-1) was performed in aortic tissues by Real Time PCR. p21-/- mice gained significantly (p < 0.01) more weight than wild type mice, triglycerides (p < 0.05) and cholesterol levels (p < 0.01) were more pronounced in the sera of p21-/- compared to wild type mice fed with high fat diet. High fat diet resulted in significantly decreased TGF-? (p < 0.02), HO-l (p < 0.02) and increased CD36 (p < 0.03) mRNA expression in aortic tissues of p21-/- mice compared to animal fed with regular diet. IFN-? mRNA expression (235 ± 11 folds) increased significantly in high fat diet fed p21-/- mice and a multifold modulation of PPAR-?(136 ± 7), p22phox, NOX-1 and Rac-1 (15–35-folds) mRNA in aortic tissues from p21-/- mice compared to the wild type mice. Severity of atherosclerotic lesions was significantly higher in p21-/- compared to wild type mice. The results demonstrate that the deficiency of p21 leads to altered expression of pro-atherogenic genes, and severe atherosclerosis in mice fed with high fat diet. This opens the possibility of p21 protein as a therapeutic tool to control progression of atherosclerosis. PMID:19604372

  6. Pitavastatin calcium improves endothelial function and delays the progress of atherosclerosis in patients with hypercholesterolemia*

    PubMed Central

    Zhao, Jing; Yan, Hui-min; Li, Ya; Wang, Jia; Han, Lu; Wang, Zhi-hao; Tang, Meng-xiong; Zhang, Wei; Zhang, Yun; Zhong, Ming

    2015-01-01

    Background: Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia (HC) is unknown. Objectives: To explore the simultaneous effects of pitavastatin calcium on brachial arterial flow-mediated vasodilatation (FMD), carotid intima-media thickness (IMT), and arterial stiffness (?), three surrogate markers of atherosclerosis were studied in HC patients. Methods: A randomized, double-blind trial was performed with 40 HC subjects who fulfilled the inclusion/exclusion criteria. Patients were given pitavastatin calcium 1 mg/d (Group 1) or 2 mg/d (Group 2) for 8 weeks. There were 20 patients in each group, and 30 gender- and age-matched healthy subjects as controls were recruited. FMD of the brachial artery, carotid IMT, and arterial stiffness indicated by ? were measured at baseline and at 8 weeks after starting pitavastatin calcium therapy using ultrasound techniques. Biochemical tests were also made on all subjects. Results: At baseline, higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), reduced FMD, and increased ? and IMT were observed in HC patients (P<0.001 for all) compared with controls. After 8 weeks, TC was decreased by 20.59%/27.56% and LDL-C 30.92%/35.64%, respectively, in comparison to baseline groups; the HC groups had reduced ? and improved endothelial function over the 8-week follow-up (P<0.05–0.001); nonetheless, no significant alterations of IMT were found (P>0.05). Significant negative interactions between TC/LDL and FMD (P<0.05–0.001), positive interactions between TC and IMT (P=0.003) and between TC/LDL and ? (P<0.001–0.000) were found. Conclusions: Treatment with pitavastatin calcium exerted favorable effects on endothelial function and arterial stiffness. It also improved carotid atherosclerosis in patients with HC. PMID:25990055

  7. The key role of histamine in the development of atherosclerosis and coronary heart disease.

    PubMed

    Clemetson, C A

    1999-01-01

    Vitamin C-deficiency is known to cause a disturbance of cholesterol metabolism. Suboptimal plasma ascorbic acid levels also cause increased blood histamine levels, which are exaggerated by sleep-lack and other forms of stress. Histaminemia causes separation of vascular endothelial cells. It is here suggested that the histaminemia of stress and ascorbate depletion combine to cause damage to the arterial endothelium and predispose to atherosclerosis, the principal cause of myocardial infarction. PMID:10342662

  8. Influence of phenotype conversion of epicardial adipocytes on the coronary atherosclerosis and its potential molecular mechanism

    PubMed Central

    Wang, Jing; Chen, Dong; Cheng, Xun-Min; Zhang, Qi-Gao; Peng, Yong-Ping; Wang, Li-Jun; He, Song-Qing; Gong, Jian-Bin

    2015-01-01

    Objective: To investigate the phenotype conversion of epicardial adipocytes and its potential molecular mechanism during the occurrence and development of coronary atherosclerosis. Methods: A total of 30 health male New Zealand white rabbits were used. In experiment group (n=15), rabbits were fed with high fat food to establish atherosclerosis animal model; rabbits in control group (n=15) were fed with normal food. Results: At week 0, UCP-1 and PPAR? mRNA expressions in EAT and sBAT were significantly higher than in eWAT, and leptin mRNA expression lower than (P<0.05). In experiment group, the mRNA expressions of UCP-1 and PPAR? reduced gradually, but leptin mRNA increased progressively in EAT (P<0.05). UCP-1 expression reduced gradually, the newly generated blood vessels reduced significantly, but leptin and RAM11 increased gradually (P<0.05). The adipocyte volume in EAT increased gradually, but the adipocyte number reduced progressively (P<0.05). The number of mitochondria with multiple crests reduced gradually in EAT; IL-6 reduced the mRNA expressions of UCP-1 and PPAR? in adipocytes of BAT in a dose dependent manner, but it increased the mRNA expressions of leptin and STAT3 (P<0.05). In the presence of IL-6, JSI-124 increased the mRNA expressions of UCP-1 and PPAR-? in adipocytes of BAT in a dose dependent manner, but it reduced the mRNA expressions of leptin and STAT3 (P<0.05). Conclusion: During the progression of atherosclerosis, there is a phenotype conversion of EAT from BAT to WAT, which further promotes the focal occurrence and development of atherosclerosis; IL-6 may activate JAK-STAT3 pathway to induce this conversion. PMID:26692919

  9. An ethanolic extract of Angelica gigas improves atherosclerosis by inhibiting vascular smooth muscle cell proliferation

    PubMed Central

    Jang, Ja Young; Kim, Jihyun; Cai, Jingmei; Kim, Youngeun; Shin, Kyungha; Kim, Tae-Su; Lee, Sung-Pyo; Park, Sung Kyeong

    2014-01-01

    The effects of an ethanolic extract of Angelica gigas (EAG) on the vascular smooth muscle cell (VSMC) proliferation and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis were investigated. Rat aortic VSMCs were stimulated with platelet-derived growth factor-BB (25 ng/mL) for the induction of DNA synthesis and cell proliferation. EAG (1-10 µg/mL) significantly inhibited both the thymidine incorporation and cell proliferation in a concentration-dependent manner. Hypercholesterolemia was induced by feeding male New Zealand white rabbits with 0.5% cholesterol in diet for 10 weeks, during which EAG (1% in diet) was given for the final 8 weeks after 2-week induction of hypercholesterolemia. Hypercholesterolemic rabbits exhibited great increases in serum total cholesterol and low-density lipoproteins (LDL) levels, and finally severe atheromatous plaque formation covering 28.4% of the arterial walls. EAG significantly increased high-density lipoproteins (HDL), slightly decreased LDL, and potentially reduced the atheroma area to 16.6%. The results indicate that EAG attenuates atherosclerosis not only by inhibiting VASC proliferation, but also by increasing blood HDL levels. Therefore, it is suggested that EAG could be an alternative or an adjunct therapy for the improvement of hypercholesterolemia and atherosclerosis. PMID:24999363

  10. An ethanolic extract of Angelica gigas improves atherosclerosis by inhibiting vascular smooth muscle cell proliferation.

    PubMed

    Jang, Ja Young; Kim, Jihyun; Cai, Jingmei; Kim, Youngeun; Shin, Kyungha; Kim, Tae-Su; Lee, Sung-Pyo; Park, Sung Kyeong; Choi, Ehn-Kyoung; Kim, Yun-Bae

    2014-06-01

    The effects of an ethanolic extract of Angelica gigas (EAG) on the vascular smooth muscle cell (VSMC) proliferation and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis were investigated. Rat aortic VSMCs were stimulated with platelet-derived growth factor-BB (25 ng/mL) for the induction of DNA synthesis and cell proliferation. EAG (1-10 µg/mL) significantly inhibited both the thymidine incorporation and cell proliferation in a concentration-dependent manner. Hypercholesterolemia was induced by feeding male New Zealand white rabbits with 0.5% cholesterol in diet for 10 weeks, during which EAG (1% in diet) was given for the final 8 weeks after 2-week induction of hypercholesterolemia. Hypercholesterolemic rabbits exhibited great increases in serum total cholesterol and low-density lipoproteins (LDL) levels, and finally severe atheromatous plaque formation covering 28.4% of the arterial walls. EAG significantly increased high-density lipoproteins (HDL), slightly decreased LDL, and potentially reduced the atheroma area to 16.6%. The results indicate that EAG attenuates atherosclerosis not only by inhibiting VASC proliferation, but also by increasing blood HDL levels. Therefore, it is suggested that EAG could be an alternative or an adjunct therapy for the improvement of hypercholesterolemia and atherosclerosis. PMID:24999363

  11. Hepatic overexpression of methionine sulfoxide reductase A reduces atherosclerosis in apolipoprotein E-deficient mice.

    PubMed

    Xu, Yan-Yong; Du, Fen; Meng, Bing; Xie, Guang-Hui; Cao, Jia; Fan, Daping; Yu, Hong

    2015-10-01

    Methionine sulfoxide reductase A (MsrA), a specific enzyme that converts methionine-S-sulfoxide to methionine, plays an important role in the regulation of protein function and the maintenance of redox homeostasis. In this study, we examined the impact of hepatic MsrA overexpression on lipid metabolism and atherosclerosis in apoE-deficient (apoE(-/-)) mice. In vitro study showed that in HepG2 cells, lentivirus-mediated human MsrA (hMsrA) overexpression upregulated the expression levels of several key lipoprotein-metabolism-related genes such as liver X receptor ?, scavenger receptor class B type I, and ABCA1. ApoE(-/-) mice were intravenously injected with lentivirus to achieve high-level hMsrA expression predominantly in the liver. We found that hepatic hMsrA expression significantly reduced plasma VLDL/LDL levels, improved plasma superoxide dismutase, and paraoxonase-1 activities, and decreased plasma serum amyloid A level in apoE(-/-) mice fed a Western diet, by significantly altering the expression of several genes in the liver involving cholesterol selective uptake, conversion and excretion into bile, TG biosynthesis, and inflammation. Moreover, overexpression of hMsrA resulted in reduced hepatic steatosis and aortic atherosclerosis. These results suggest that hepatic MsrA may be an effective therapeutic target for ameliorating dyslipidemia and reducing atherosclerosis-related cardiovascular diseases. PMID:26318157

  12. Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets

    PubMed Central

    Ramji, Dipak P.; Davies, Thomas S.

    2015-01-01

    Atherosclerosis, a chronic inflammatory disorder of the arteries, is responsible for most deaths in westernized societies with numbers increasing at a marked rate in developing countries. The disease is initiated by the activation of the endothelium by various risk factors leading to chemokine-mediated recruitment of immune cells. The uptake of modified lipoproteins by macrophages along with defective cholesterol efflux gives rise to foam cells associated with the fatty streak in the early phase of the disease. As the disease progresses, complex fibrotic plaques are produced as a result of lysis of foam cells, migration and proliferation of vascular smooth muscle cells and continued inflammatory response. Such plaques are stabilized by the extracellular matrix produced by smooth muscle cells and destabilized by matrix metalloproteinase from macrophages. Rupture of unstable plaques and subsequent thrombosis leads to clinical complications such as myocardial infarction. Cytokines are involved in all stages of atherosclerosis and have a profound influence on the pathogenesis of this disease. This review will describe our current understanding of the roles of different cytokines in atherosclerosis together with therapeutic approaches aimed at manipulating their actions. PMID:26005197

  13. Dipeptidyl Peptidase 4: A New Link between Diabetes Mellitus and Atherosclerosis?

    PubMed Central

    da Silva Júnior, Wellington Santana; de Godoy-Matos, Amélio Fernando; Kraemer-Aguiar, Luiz Guilherme

    2015-01-01

    Type 2 diabetes mellitus (T2DM) has become one of the most prevalent noncommunicable diseases in the past years. It is undoubtedly associated with atherosclerosis and increased risk for cardiovascular diseases. Incretins, which are intestinal peptides secreted during digestion, are able to increase insulin secretion and its impaired function and/or secretion is involved in the pathophysiology of T2DM. Dipeptidyl peptidase 4 (DPP4) is an ubiquitous enzyme that regulates incretins and consequently is related to the pathophysiology of T2DM. DPP4 is mainly secreted by endothelial cells and acts as a regulatory protease for cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. In T2DM, the activity of DPP4 seems to be increased and there are a growing number of in vitro and in vivo studies suggesting that this enzyme could be a new link between T2DM and atherosclerosis. Gliptins are a new class of pharmaceutical agents that acts by inhibiting DPP4. Thus, it is expected that gliptin represents a new pharmacological approach not only for reducing glycemic levels in T2DM, but also for the prevention and treatment of atherosclerotic cardiovascular disease in diabetic subjects. We aimed to review the evidences that reinforce the associations between DPP4, atherosclerosis, and T2DM. PMID:26146634

  14. Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model

    PubMed Central

    Ludewig, Burkhard; Freigang, Stefan; Jäggi, Martin; Kurrer, Michael O.; Pei, Yao-Chang; Vlk, Lenka; Odermatt, Bernhard; Zinkernagel, Rolf M.; Hengartner, Hans

    2000-01-01

    Arterial inflammatory responses are thought to be a significant component of atherosclerotic disease. We describe here, using a transgenic approach, the mutual perpetuation of immune-mediated arterial inflammation and cholesterol-induced atherosclerosis. Mice expressing the bacterial transgene ?-galactosidase exclusively in cardiomyocytes and in smooth muscle cells in lung arteries and the aorta (SM-LacZ), and hypercholesterolemic apolipoprotein E-deficient SM-LacZ mice (SM-LacZ/apoE?/?) developed myocarditis and arteritis after immunization with dendritic cells presenting a ?-galactosidase-derived immunogenic peptide. Hypercholesterolemia amplified acute arteritis and perpetuated chronic arterial inflammation in SM-LacZ/apoE?/? mice, but had no major impact on acute myocarditis or the subsequent development of dilated cardiomyopathy. Conversely, arteritis significantly accelerated cholesterol-induced atherosclerosis. Taken together, these data demonstrate that the linkage of immune-mediated arteritis and hypercholesterolemia favors initiation and maintenance of atherosclerotic lesion formation. Therapeutic strategies to prevent or disrupt such self-perpetuating vicious circles may be crucial for the successful treatment of atherosclerosis. PMID:11050173

  15. Surface Roughness Detection of Arteries via Texture Analysis of Ultrasound Images for Early Diagnosis of Atherosclerosis

    PubMed Central

    Niu, Lili; Qian, Ming; Yang, Wei; Meng, Long; Xiao, Yang; Wong, Kelvin K. L.; Abbott, Derek; Liu, Xin; Zheng, Hairong

    2013-01-01

    There is a strong research interest in identifying the surface roughness of the carotid arterial inner wall via texture analysis for early diagnosis of atherosclerosis. The purpose of this study is to assess the efficacy of texture analysis methods for identifying arterial roughness in the early stage of atherosclerosis. Ultrasound images of common carotid arteries of 15 normal mice fed a normal diet and 28 apoE?/? mice fed a high-fat diet were recorded by a high-frequency ultrasound system (Vevo 2100, frequency: 40 MHz). Six different texture feature sets were extracted based on the following methods: first-order statistics, fractal dimension texture analysis, spatial gray level dependence matrix, gray level difference statistics, the neighborhood gray tone difference matrix, and the statistical feature matrix. Statistical analysis indicates that 11 of 19 texture features can be used to distinguish between normal and abnormal groups (p<0.05). When the 11 optimal features were used as inputs to a support vector machine classifier, we achieved over 89% accuracy, 87% sensitivity and 93% specificity. The accuracy, sensitivity and specificity for the k-nearest neighbor classifier were 73%, 75% and 70%, respectively. The results show that it is feasible to identify arterial surface roughness based on texture features extracted from ultrasound images of the carotid arterial wall. This method is shown to be useful for early detection and diagnosis of atherosclerosis. PMID:24146940

  16. Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets.

    PubMed

    Ramji, Dipak P; Davies, Thomas S

    2015-12-01

    Atherosclerosis, a chronic inflammatory disorder of the arteries, is responsible for most deaths in westernized societies with numbers increasing at a marked rate in developing countries. The disease is initiated by the activation of the endothelium by various risk factors leading to chemokine-mediated recruitment of immune cells. The uptake of modified lipoproteins by macrophages along with defective cholesterol efflux gives rise to foam cells associated with the fatty streak in the early phase of the disease. As the disease progresses, complex fibrotic plaques are produced as a result of lysis of foam cells, migration and proliferation of vascular smooth muscle cells and continued inflammatory response. Such plaques are stabilized by the extracellular matrix produced by smooth muscle cells and destabilized by matrix metalloproteinase from macrophages. Rupture of unstable plaques and subsequent thrombosis leads to clinical complications such as myocardial infarction. Cytokines are involved in all stages of atherosclerosis and have a profound influence on the pathogenesis of this disease. This review will describe our current understanding of the roles of different cytokines in atherosclerosis together with therapeutic approaches aimed at manipulating their actions. PMID:26005197

  17. C-reactive protein promotes atherosclerosis by increasing LDL transcytosis across endothelial cells

    PubMed Central

    Bian, Fang; Yang, Xiaoyan; Zhou, Fan; Wu, Pin-Hui; Xing, Shasha; Xu, Gao; Li, Wenjing; Chi, Jiangyang; Ouyang, Changhan; Zhang, Yonghui; Xiong, Bin; Li, Yongsheng; Zheng, Tao; Wu, Dan; Chen, Xiaoqian; Jin, Si

    2014-01-01

    Background and Purpose The retention of plasma low-density lipoprotein (LDL) particles in subendothelial space following transcytosis across the endothelium is the initial step of atherosclerosis. Whether or not C-reactive protein (CRP) can directly affect the transcytosis of LDL is not clear. Here we have examined the effect of CRP on transcytosis of LDL across endothelial cells and have explored the underlying mechanisms. Experimental Approach Effects of CRP on transcytosis of FITC-labelled LDL were examined with human umbilical vein endothelial cells and venous rings in vitro and, in vivo, ApoE-/- mice. Laser scanning confocal microscopy, immunohistochemistry and Oil Red O staining were used to assay LDL. Key Results CRP increased transcytosis of LDL. An NADPH oxidase inhibitor, diphenylene iodonium, and the reducing agent, dithiothreitol partly or completely blocked CRP-stimulated increase of LDL transcytosis. The PKC inhibitor, bisindolylmaleimide I and the Src kinase inhibitor, PP2, blocked the trafficking of the molecules responsible for transcytosis. Confocal imaging analysis revealed that CRP stimulated LDL uptake by endothelial cells and vessel walls. In ApoE-/- mice, CRP significantly promoted early changes of atherosclerosis, which were blocked by inhibitors of transcytosis. Conclusions and Implications CRP promoted atherosclerosis by directly increasing the transcytosis of LDL across endothelial cells and increasing LDL retention in vascular walls. These actions of CRP were associated with generation of reactive oxygen species, activation of PKC and Src, and translocation of caveolar or soluble forms of the N-ethylmaleimide-sensitive factor attachment protein. PMID:24517733

  18. The Jeremiah Metzger Lecture. Pathogenesis of atherosclerosis: redox as a unifying mechanism.

    PubMed Central

    Alexander, R. Wayne

    2003-01-01

    Excessive production of reactive oxygen species (ROS) occurs in many diseases and oxidation may be a common disease mechanism generally. The original "oxidation hypothesis" concerning the pathogenesis of atherosclerosis was posited in the context of the putative central role of oxidized LDL in the process. Atherosclerosis has three major characteristic features: inflammation with accumulation of T-cells and, in particular, monocytes, which become lipid rich foam cells; remodeling of the arterial wall; and the non-random localization of lesions to areas of disturbed flow or of low shear stress. The evidence is reviewed that each of these characteristics can be attributed to excessive ROS, which are derived from cellular oxidases, especially, the NAD(P)H oxidases. This expanded concept of the central role of oxidation in the pathogenesis of atherosclerosis has led to a renewed and intense interest in the potential role of antioxidants in therapy. The vascular protective effects of existing drugs such as statins and ACE inhibitors that are not related to serum lipid alterations are attributed to their indirect but effective roles as antioxidants. These data as well as evidence that newly developed antioxidant drugs show promise, not only in experimental animals but also clinically, are reviewed. Images Fig. 1 p276-a Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:12813926

  19. A Pathological Study of the Epidemiology of Atherosclerosis in Mexico City

    PubMed Central

    Rodríguez-Saldaña, Joel; Rodriguez-Flores, Marcela; Cantú-Brito, Carlos; Aguirre-Garcia, Jesús

    2014-01-01

    Objective. To examine the frequency and patterns of association of cardiovascular risk factors with atherosclerosis in five different arterial territories at post-mortem in Mexico City. Methods. We obtained five arterial territories arteries (circle of Willis, coronary, carotid, renal, and aorta) of 185 men and women 0 to 90 years of age who underwent autopsy at the Medical Forensic Service of Mexico City. We determined the prevalence and extent of atherosclerotic lesions by histopathology according to the classification of the American Heart Association as early (types I–III) and advanced (types IV–VI), and according to the degree of stenosis and correlated with cardiovascular risk factors. Results. Atherosclerotic lesions were identified in at least one arterial territory in 181 subjects (97.8%), with involvement of two ore more territories in 178 subjects (92.2%). Advanced lesions were observed in 36% and 67% of subjects under 15 and between 16 and 35 years, respectively. Any degree of atherosclerosis was associated with the presence of diabetes mellitus, hypertension, overweight, obesity, and smoking, and to a greater extent with the presence of two or more risk factors (P < 0.001). However, emerging and advanced athersoclerosis was observed in 53% and 20% people with no risk factors. Conclusions. The study shows a high prevalence of atherosclerosis in all age groups and both sexes. There is considerable development of atherosclerotic disease in subjects without known risk factors. PMID:24719773

  20. Clinical potential of vorapaxar in cardiovascular risk reduction in patients with atherosclerosis

    PubMed Central

    Diehl, Philipp; Bode, Christoph; Duerschmied, Daniel

    2015-01-01

    Vorapaxar (ZONTIVITY™, formerly known as SCH 530348) is a specific, orally active antagonist of the protease-activated receptor-1 (PAR-1) on platelets. It inhibits thrombin-induced platelet activation by binding to the ectodomain of PAR-1. After animal studies and Phase II studies showed that vorapaxar sufficiently inhibits platelet activation without significantly increasing bleeding complications, safety and efficacy of vorapaxar were assessed in two large multicenter trials in patients with coronary artery disease and atherosclerosis. The Thrombin-Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndromes (TRACER) trial investigated safety and efficacy of vorapaxar in patients with an acute coronary syndrome without ST-segment elevation. The Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50 (TRA 2°P-TIMI 50) investigated atherothrombotic events in patients with stable atherosclerosis. Results of both studies suggested that vorapaxar given in addition to standard antiplatelet therapy can reduce atherothrombotic events, but increases the risk of mild and moderate bleeding complications. This review article summarizes the main results of TRACER and TRA 2°P-TIMI 50 and suggests patient cohorts that might benefit from treatment with vorapaxar in addition to standard antiplatelet therapy. PMID:26346960

  1. [The role of calcium ions in the pathomechanism of the artery calcification accompanying atherosclerosis].

    PubMed

    Ma?ecki, Rafa?; Adamiec, Rajmund

    2005-01-01

    Artery calcification occurring in atherosclerosis is connected with a high risk of cardiovascular events. Quantitative calcification evaluation using electron beam tomography indicated a correlation between artery calcification and well-known cardiovascular risk factors, i.e. smoking, obesity, and hyperlipidemia. Elevated calcium scores are especially observed in diabetic patients, which may even explain the higher mortality in this group. Calcification leads to increased blood vessel rigidity and, consequently, elevated arterial vascular resistance and left ventricular hypertrophy. An increased risk of plaque rupture in relation to calcium-rich atherosclerotic lesions was not proved. Plaque rupture and thromboembolitic complications are probably higher in the case of lipid-rich lesions. Atherosclerotic calcification is an active process in which many cells (monocytes/macrophages, vascular smooth muscle cells, and endothelial cells) participate. Many substances and transcription factors normally participating in the bone remodeling process are found in calcified atherosclerotic lesions (e.g. Cbfa-1, osteocalcin, alkaline phosphatase, BMP-2, osteopontin, osteoprotegrin, and RANKL). On monocytes, cells playing an important role in atherosclerosis progression, the presence of a calcium-sensing receptor (CaR) has been demonstrated. Increase in monocyte chemotaxis and increased interleukin 6 secretion in response to extracellular calcium were observed. Monocytes also directly and indirectly enhance vascular calcification. Immune cells and cytokines participating in vascular calcification are connected in one pathogenetic mechanism, i.e. atherosclerosis as an inflammatory disease and calcification. PMID:15761385

  2. Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production.

    PubMed

    Guo, Yanhong; Fan, Yanbo; Zhang, Jifeng; Lomberk, Gwen A; Zhou, Zhou; Sun, Lijie; Mathison, Angela J; Garcia-Barrio, Minerva T; Zhang, Ji; Zeng, Lixia; Li, Lei; Pennathur, Subramaniam; Willer, Cristen J; Rader, Daniel J; Urrutia, Raul; Chen, Y Eugene

    2015-10-01

    Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Krüppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol (HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the effects of both KLF14 overexpression and genetic inactivation and determined that KLF14 regulates plasma HDL-C levels and cholesterol efflux capacity by modulating hepatic ApoA-I production. Hepatic-specific Klf14 deletion in mice resulted in decreased circulating HDL-C levels. In an attempt to pharmacologically target KLF14 as an experimental therapeutic approach, we identified perhexiline, an approved therapeutic small molecule presently in clinical use to treat angina and heart failure, as a KLF14 activator. Indeed, in WT mice, treatment with perhexiline increased HDL-C levels and cholesterol efflux capacity via KLF14-mediated upregulation of ApoA-I expression. Moreover, perhexiline administration reduced atherosclerotic lesion development in apolipoprotein E-deficient mice. Together, these results provide comprehensive insight into the KLF14-dependent regulation of HDL-C and subsequent atherosclerosis and indicate that interventions that target the KLF14 pathway should be further explored for the treatment of atherosclerosis. PMID:26368306

  3. Exosomes: emerging roles in communication between blood cells and vascular tissues during atherosclerosis

    PubMed Central

    Huber, Heinrich J.; Holvoet, Paul

    2015-01-01

    Purpose of review Microvesicles, in general, and exosomes together with their delivered content in particular, are now being widely recognized as key players in atherosclerosis. We have previously reviewed the role of microvesicles in atherosclerosis pathogenesis, diagnosis and therapy. Here, we focus on the roles of exosomes and discuss their emergent role in mediating activation and response to inflammation, vessel infiltration and induction of coagulation. We will finally give an outlook to discuss novel detection techniques and systems biology based data analyses to investigate exosome-mediated cell-to-cell communication. Recent findings Recent research points to a role of exosomes in delivering apoptotic and inflammatory content between blood cells and vascular cells, with a potential contribution of exosomes secreted by adipose tissue. An atheroprotective role of exosomes in response to coagulation that may contrast with the procoagulatory role of platelet-derived larger microvesicles is envisaged. New detection and separation methods and systems biology techniques are emerging. Conclusion We project that the development of novel detection, separation and analysis mechanism and systems-based analysis methods will further unravel the paracrine and endocrine ‘communication protocol’ between cellular players in atherosclerosis, mediating inflammation, oxidative stress and apoptosis. PMID:26309202

  4. Ceramide as a Mediator of Non-Alcoholic Fatty Liver Disease and Associated Atherosclerosis

    PubMed Central

    Kasumov, Takhar; Li, Ling; Li, Min; Gulshan, Kailash; Kirwan, John P.; Liu, Xiuli; Previs, Stephen; Willard, Belinda; Smith, Jonathan D.; McCullough, Arthur

    2015-01-01

    Cardiovascular disease (CVD) is a serious comorbidity in nonalcoholic fatty liver disease (NAFLD). Since plasma ceramides are increased in NAFLD and sphingomyelin, a ceramide metabolite, is an independent risk factor for CVD, the role of ceramides in dyslipidemia was assessed using LDLR-/- mice, a diet-induced model of NAFLD and atherosclerosis. Mice were fed a standard or Western diet (WD), with or without myriocin, an inhibitor of ceramide synthesis. Hepatic and plasma ceramides were profiled and lipid and lipoprotein kinetics were quantified. Hepatic and intestinal expression of genes and proteins involved in insulin, lipid and lipoprotein metabolism were also determined. WD caused hepatic oxidative stress, inflammation, apoptosis, increased hepatic long-chain ceramides associated with apoptosis (C16 and C18) and decreased very-long-chain ceramide C24 involved in insulin signaling. The plasma ratio of ApoB/ApoA1 (proteins of VLDL/LDL and HDL) was increased 2-fold due to increased ApoB production. Myriocin reduced hepatic and plasma ceramides and sphingomyelin, and decreased atherosclerosis, hepatic steatosis, fibrosis, and apoptosis without any effect on oxidative stress. These changes were associated with decreased lipogenesis, ApoB production and increased HDL turnover. Thus, modulation of ceramide synthesis may lead to the development of novel strategies for the treatment of both NAFLD and its associated atherosclerosis. PMID:25993337

  5. Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits

    PubMed Central

    Ram, Heera; Jatwa, Rameshwar; Purohit, Ashok

    2014-01-01

    Acacia senegal L. (Fabaceae) seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500?mg/kg body weight/day mixed with coconut oil) for 15 days. Circulating total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides, and VLDL-cholesterol (VLDL-C) levels; atherogenic index (AI); cardiac lipid peroxidation (LPO); planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta (6.34 ± 0.72) and increased lumen volume (51.65 ± 3.66), administration with ethanolic extract of Acacia senegal seeds (500?mg/kg/day, p.o.) for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics. PMID:25544897

  6. Amelioration of Atherosclerosis by the New Medicinal Mushroom Grifola gargal Singer.

    PubMed

    Harada, Etsuko; D'Alessandro-Gabazza, Corina N; Toda, Masaaki; Morizono, Toshihiro; Chelakkot-Govindalayathil, Ayshwarya-Lakshmi; Roeen, Ziaurahman; Urawa, Masahito; Yasuma, Taro; Yano, Yutaka; Sumiya, Toshimitsu; Gabazza, Esteban C

    2015-08-01

    The beneficial effects of edible mushrooms for improving chronic intractable diseases have been documented. However, the antiatherogenic activity of the new medicinal mushroom Grifola gargal is unknown. Therefore, we evaluated whether Grifola gargal can prevent or delay the progression of atherosclerosis. Atherosclerosis was induced in ApoE lipoprotein-deficient mice by subcutaneous infusion of angiotensin II. Grifola gargal extract (GGE) was prepared and intraperitoneally injected. The weight of heart and vessels, dilatation/atheroma formation of thoracic and abdominal aorta, the percentage of peripheral granulocytes, and the blood concentration of MCP-1/CCL2 were significantly reduced in mice treated with GGE compared to untreated mice. By contrast, the percentage of regulatory T cells and the plasma concentration of SDF-1/CXCL12 were significantly increased in mice treated with the mushroom extract compared to untreated mice. In vitro, GGE significantly increased the secretion of SDF-1/CXCL12, VEGF, and TGF-?1 from fibroblasts compared to control. This study demonstrated for the first time that Grifola gargal therapy can enhance regulatory T cells and ameliorate atherosclerosis in mice. PMID:25799023

  7. Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease

    PubMed Central

    Minear, Mollie A.; Crosslin, David R.; Sutton, Beth S.; Connelly, Jessica J.; Nelson, Sarah C.; Gadson-Watson, Shera; Wang, Tianyuan; Seo, David; Vance, Jeffrey M.; Sketch, Michael H.; Haynes, Carol; Goldschmidt-Clermont, Pascal J.; Shah, Svati H.; Kraus, William E.; Hauser, Elizabeth R.

    2013-01-01

    Tenascin-C (TNC) is an extracellular matrix protein implicated in biological processes important for atherosclerotic plaque development and progression, including smooth muscle cell migration and proliferation. Previously, we observed differential expression of TNC in atherosclerotic aortas compared with healthy aortas. The goal of this study was to investigate whether common genetic variation within TNC is associated with risk of atherosclerosis and coronary artery disease (CAD) in three independent datasets. We genotyped 35 single nucleotide polymorphisms (SNPs), including 21 haplotype tagging SNPs, in two of these datasets: human aorta tissue samples (n = 205) and the CATHGEN cardiovascular study (n = 1,325). Eleven of these 35 SNPs were then genotyped in a third dataset, the GENECARD family study of early-onset CAD (n = 879 families). Three SNPs representing a block of linkage disequilibrium, rs3789875, rs12347433, and rs4552883, were significantly associated with athero sclerosis in multiple datasets and demonstrated consistent, but suggestive, genetic effects in all analyses. In combined analysis rs3789875 and rs12347433 were statistically significant after Bonferroni correction for 35 comparisons, p = 2 × 10?6 and 5 × 10?6, respectively. The SNP rs12347433 is a synonymous coding SNP and may be biologically relevant to the mechanism by which tenascin-C influences the pathophysiology of CAD and atherosclerosis. This is the first report of genetic association between polymorphisms in TNC and atherosclerosis or CAD. PMID:21298289

  8. Optimization of a Low Magnesium, Cholesterol-Containing Diet for the Development of Atherosclerosis in Rabbits.

    PubMed

    Smith, Brendon W; King, Jennifer L; Miller, Rita J; Blue, James P; Sarwate, Sandhya; O'Brien, William D; Erdman, John W

    2013-02-01

    The cholesterol-fed rabbit is useful for atherosclerosis research. We describe development of a low-magnesium (Mg) cholesterol-containing diet to accelerate atherosclerosis in this model. Male New Zealand White rabbits were fed either chow or one of four atherogenic diets: 1% cholesterol 10% fat 0.11% Mg, 1% cholesterol 10% fat 0.40% Mg, 2% cholesterol 20% fat 0.11% Mg, or 2% cholesterol 20% fat 0.40% Mg. While feed intake decreased in cholesterol-fed rabbits, they were able to maintain their body weights. Rabbits consuming cholesterol experienced profound hypercholesterolemia and tissue lipid accumulation, with plasma cholesterol levels above 1500 mg/dl for all groups at the completion of the study. Liver and spleen lipid content and liver cholesterol content also increased. Aortic arch atheroma thickness was greatest in 1% cholesterol 10% fat 0.11% Mg animals. Tissue Mg levels decreased in cholesterol-fed animals compared to chow-fed controls, despite equal or greater serum Mg levels. Our results indicate that the 1% cholesterol 10% fat 0.11% Mg diet was optimal at promoting hypercholesterolemia and atherosclerosis while minimizing health complications for the animals. The low Mg cholesterol diet will be useful to other biomedical researchers interested in utilizing the rabbit for cardiovascular disease research. PMID:24672587

  9. Metformin Beyond Diabetes: Pleiotropic Benefits of Metformin in Attenuation of Atherosclerosis

    PubMed Central

    Forouzandeh, Farshad; Salazar, Gloria; Patrushev, Nikolay; Xiong, Shiqin; Hilenski, Lula; Fei, Baowei; Alexander, R. Wayne

    2014-01-01

    Background Clinical studies show that metformin attenuates all?cause mortality and myocardial infarction compared with other medications for type 2 diabetes, even at similar glycemic levels. However, there is paucity of data in the euglycemic state on the vasculoprotective effects of metformin. The objectives of this study are to evaluate the effects of metformin on ameliorating atherosclerosis. Methods and Results Using ApoE?/? C57BL/6J mice, we found that metformin attenuates atherosclerosis and vascular senescence in mice fed a high?fat diet and prevents the upregulation of angiotensin II type 1 receptor by a high?fat diet in the aortas of mice. Thus, considering the known deleterious effects of angiotensin II mediated by angiotensin II type 1 receptor, the vascular benefits of metformin may be mediated, at least in part, by angiotensin II type 1 receptor downregulation. Moreover, we found that metformin can cause weight loss without hypoglycemia. We also found that metformin increases the antioxidant superoxide dismutase?1. Conclusion Pleiotropic effects of metformin ameliorate atherosclerosis and vascular senescence. PMID:25527624

  10. Detection of Marek's disease virus DNA in Japanese quail susceptible to atherosclerosis

    SciTech Connect

    Pyrzak, R.; Shih, J.C.H.

    1986-03-01

    Marek's disease virus (MDV) was demonstrated as an etiological agent which causes atherosclerosis in the chicken. Since herpes viruses are ubiquitous, incidences of viral atherogenesis in humans and other animals were speculated. In this laboratory, the atherosclerosis susceptible (SUS) and resistant (RES) Japanese quail were developed as the animal model for atherosclerosis research. The susceptibility of the animal might be due to an infection of MDV or a related quail herpes virus (QHV). An initial attempt to isolate viruses from quail and an agar gel precipitin test for MDC were not positive. A DNA hybridization technique was used to determine whether the MDC-DNA existed in the quail cell. The gene library of MDV EcoRl DNA fragments was used to prepare the DNA probe, labeled with (/sup 32/P) by nick translation. Dot hybridizations were carried out by mixing the MDV-DNA probe with DNAs isolated from quail tissues. A high stringent condition was used. From this experiment it was found that the tissues from the SUS quail were hybridization positive, but most of them from RES quail were negative. When aortas were compared, the severe atherosclerotic had a strong hybridization (3-4 cop. of genome/cell) whereas the others hybridized moderately (1 cop./cell). It was concluded that genes from MDV or a QHV indeed existed in Japanese quail.

  11. Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model.

    PubMed

    Ludewig, B; Freigang, S; Jäggi, M; Kurrer, M O; Pei, Y C; Vlk, L; Odermatt, B; Zinkernagel, R M; Hengartner, H

    2000-11-01

    Arterial inflammatory responses are thought to be a significant component of atherosclerotic disease. We describe here, using a transgenic approach, the mutual perpetuation of immune-mediated arterial inflammation and cholesterol-induced atherosclerosis. Mice expressing the bacterial transgene beta-galactosidase exclusively in cardiomyocytes and in smooth muscle cells in lung arteries and the aorta (SM-LacZ), and hypercholesterolemic apolipoprotein E-deficient SM-LacZ mice (SM-LacZ/apoE(-/-)) developed myocarditis and arteritis after immunization with dendritic cells presenting a beta-galactosidase-derived immunogenic peptide. Hypercholesterolemia amplified acute arteritis and perpetuated chronic arterial inflammation in SM-LacZ/apoE(-/-) mice, but had no major impact on acute myocarditis or the subsequent development of dilated cardiomyopathy. Conversely, arteritis significantly accelerated cholesterol-induced atherosclerosis. Taken together, these data demonstrate that the linkage of immune-mediated arteritis and hypercholesterolemia favors initiation and maintenance of atherosclerotic lesion formation. Therapeutic strategies to prevent or disrupt such self-perpetuating vicious circles may be crucial for the successful treatment of atherosclerosis. PMID:11050173

  12. Methotrexate, Cyclosporine A, and Biologics Protect against Atherosclerosis in Rheumatoid Arthritis

    PubMed Central

    Kruszewski, Robert; Juszkiewicz, Aleksandra; Raczkiewicz, Anna; Bachta, Artur; T?ustochowicz, Ma?gorzata; Staniszewska-Varga, Jadwiga; K?os, Krzysztof; Duda, Krzysztof; Bogus?awska-Walecka, Romana; P?oski, Rafa?; T?ustochowicz, Witold

    2015-01-01

    Introduction. The risk of cardiovascular disease is increased in rheumatoid arthritis (RA). A meta-analysis showed increased intima media thickness (IMT) in RA. It has been shown that disease modifying antirheumatic drugs (DMARDs) may influence the progression of atherosclerosis. However, it was suggested that biologics may be more efficient than other DMARDs (including methotrexate—MTX) in protecting against atherosclerosis. Objectives. The aim of this study was to assess the influence of different RA characteristics and treatment regimens on IMT and atherosclerotic plaques. Patients and Methods. 317 RA patients and 111 controls were included in the study. IMT was measured in carotid (CIMT) and femoral (FIMT) arteries. Arteries were screened for the presence of plaques. Results. CIMT, FIMT, and prevalence of plaques were lower in patients treated with methotrexate (MTX) ? 20?mg/wk, cyclosporine (CsA), or biologics than in patients treated with lower doses of MTX and other disease modifying antirheumatic drugs. No differences in IMT between patients treated with MTX ? 20?mg/wk, biologics, or CsA were found. Conclusions. We found a beneficial effect of MTX ? 20?mg/wk, biologics, and CsA on atherosclerosis. We do not confirm a stronger influence of biologics on IMT compared with therapeutic doses of MTX. PMID:26090499

  13. Atherosclerosis Susceptibility in Mice Is Independent of the V1 Immunoglobulin Heavy Chain Gene

    PubMed Central

    Centa, Monica; Gruber, Sabrina; Nilsson, Daniel; Polyzos, Konstantinos A.; Johansson, Daniel K.; Hansson, Göran K.; Ketelhuth, Daniel F.J.; Binder, Christoph J.

    2016-01-01

    Objective— The V1 (VHS107.1.42) immunoglobulin heavy chain gene is thought to be critical in producing IgM natural antibodies of the T15-idiotype that protect against both atherosclerosis and infection from Streptococcus pneumoniae. Our aim was to determine whether genetic loss of the V1 gene increased atherosclerotic plaque burden in vivo because of a reduction in the T15-idiotype or other atheroprotective antibodies. Approach and Results— We crossed VHS107.1.42-deficient mice with the atherosclerosis-prone Apoe?/? and Ldlr?/? strains. Although these double knockout strains manifested no defects in B-cell development, we did observe a substantial reduction in early immune responses against phosphocholine after immunization. However, the titers of plasma antibodies reacting against defined atherosclerotic antigens such as oxidized low-density lipoprotein, as well as the T15-idiotype, were unaffected by loss of the VHS107.1.42 gene in hypercholesterolemic mice. Furthermore, we observed no increase in atherosclerotic lesion formation, either within the aortic arch or aortic root. Robust deposition of IgM within atherosclerotic plaques could also be readily observed in both control and experimental mice. Conclusions— Our data indicate that IgM-dependent protection against atherosclerosis is unlikely to be dependent on antibodies that use the VHS107.1.42 gene, in contrast to the acute immune response conferred by this heavy chain in the response to phosphocholine and in providing resistance against lethal S pneumoniae infection. PMID:26564818

  14. A formula for charmonium suppression

    E-print Network

    C. Pena; D. Blaschke

    2011-08-21

    In this work a formula for charmonium suppression obtained by Matsui in 1989 is analytically generalized for the case of complex c-cbar potential described by a 3-dimensional and isotropic time-dependent harmonic oscillator (THO). It is suggested that under certain conditions the formula can be applied to describe J/\\psi suppression in heavy-ion collisions at CERN-SPS, RHIC, and LHC with the advantage of analytical tractability.

  15. Size of attentional suppressive surround.

    PubMed

    Yoo, Sang-Ah; Tsotsos, John; Fallah, Mazyar

    2015-09-01

    The Selective Tuning (ST) model (Tsotsos, 1995) proposed that the visual focus of attention is accompanied by a suppressive surround in spatial and feature dimensions. Follow-up studies have provided behavioural and neurophysiological evidence for this proposal (Carrasco, 2011; Tsotsos, 2011). ST also predicts that the size of the suppressive surround is determined by the level of processing within the visual hierarchy. We, thus, hypothesized that the size of the suppressive surround corresponds to the receptive field size of a neuron that best represents the attended stimulus. We conducted a free-viewing visual search task to test this hypothesis and used two different types of features processed at different levels - (early ventral) orientation and (late ventral) Greebles (Gauthier & Tarr, 1997). The sizes of search displays and stimuli were scaled depending on the feature levels to match the receptive field size of targeted neurons (V2 and LO). We tracked participants' eye movements during free-viewing visual search to find rapid return saccades from a distractor to a target. During search, if attention falls on a distractor (D1) such that a target lies within its suppressive surround, that target is invisible until attention is released. An eye movement then reveals the target and triggers a return saccade (Sheinberg & Logothetis, 2001). In other words, shifting gaze from D1 to another distractor (D2) releases the target from the suppression and a short latency (return) saccade to target occurs. The distribution of distances between the target and D1 when return saccades occur provides a measure for the size of the suppressive surround. Searching for Greebles produced much larger suppressive surrounds than orientation. This indicates that the size of the suppressive surround reflects the processing level of the attended stimulus supporting ST's original prediction. Meeting abstract presented at VSS 2015. PMID:26326949

  16. The therapeutic advantage of combination antihypertensive drug therapy using amlodipine and irbesartan in hypertensive patients: Analysis of the post-marketing survey data from PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; safety and efficacy in patients with hypertension) study.

    PubMed

    Ishimitsu, Toshihiko; Fukuda, Hirofumi; Uchida, Masako; Ishibashi, Kazushi; Sato, Fusako; Nukui, Kazuhiko; Nagao, Munehiko

    2015-11-01

    Two-thirds of hypertensive patients need a combination antihypertensive therapy to achieve the target blood pressure (BP). The PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; Safety and efficacy in paTieNts with hypERtension) study is a prospective specific clinical use survey examining the efficacy and safety of 12-week treatment with amlodipine (AML) and Angiotensin II Receptor Blocker (ARB) in 5900 hypertensive patients. The current analysis was performed as to the BP control, adverse reactions, and the effects on laboratory data in patients treated with the combination of AML and irbesartan (IRB), namely the patients added AML to already taking IRB (AML add-on group, n?=?1202) and the patients added IRB to AML (IRB add-on group, n?=?1050). Both study groups showed distinct decreases in office BP at 4 week (p?7?mg/dl. The incidence of adverse reactions was as few as 1.11% and there were no severe adverse reactions which hampered the continuation of combination therapy. In conclusion, combination antihypertensive therapy with AML and IRB effectively lowers BP without particular safety problems, reduces serum uric acid especially in patients with hyperuricemia and exhibits renoprotective effects in patients with chronic kidney disease. PMID:25978131

  17. The Role of Hemostatic Factors in Atherosclerosis in Patients with Chronic Renal Disease

    PubMed Central

    Zahran, Manal; Nasr, Fatma Mohammed; Metwaly, Amna Ahmed; El- Sheikh, Noha; Khalil, Nevine Sherif Ali; Harba, Tarek

    2015-01-01

    Introduction: Atherosclerotic cardiovascular disease remains the leading cause of increased morbidity and mortality observed in chronic kidney disease (CKD) patients. Endothelial dysfunction (ED) is thought to be a key initial event in the development of atherosclerosis. The aim of this study was to evaluate the potential role of hemostatic factors in atherosclerosis, thrombosis and cardiovascular complications in patients suffering from chronic renal disease. Methods: The study was conducted on 50 renal patients divided into two groups of equal size. Group 1 consisted of 25 patients with end-stage renal disease (ESRD) on regular hemodialysis. Group 2 consisted of 25 chronic renal disease patients on conservative treatment. Twenty age- and sex-matched healthy subjects were included in the study to serve as a control group. Thrombomodulin (TM), von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and hsCRP were assessed. High-resolution B-mode ultrasonography of both the common and internal carotid arteries to measure carotid intima media thickness (CIMT) was performed on all subjects. Results: There were highly significant increases in hsCRP, TM, vWF, tPA and PAI-1 in both patient groups compared to the control group (P<0.01 for all except for TM between group 2 and 3 P<0.05) with significant increase in group 1 compared to group 2 (P<0.01). In addition, there was a highly significant increase in CIMT in both patient groups compared to the control group (P<0.01) with a significant increase in group 1 compared to group 2 (P<0.05). The study revealed significant positive correlation of hemostatic factors (TM, vWf, PAI-1 & t-PA) with creatinine, urea, hsCRP & CIMT. Conclusion: CKD patients have increased risk of atherosclerosis as measured by CIMT, which is used as a surrogate marker of early atherosclerosis and has been shown to be a strong predictor of future myocardial infarction and stroke. They have high levels of TM, vWF, tPA, PAI-1 that correlate with kidney function, hsCRP and CIMT. Therefore, these abnormalities in hemostasis may account for the increased risk of atherothrombosis in these patients. The elevated hsCRP levels and their correlation to hemostatic factors and CIMT might provide an important clue to link a systemic marker of inflammation to atherosclerosis. Further research is required to better understand the procoagulant state in patients with CKD. PMID:26435827

  18. TonEBP suppresses adipogenesis and insulin sensitivity by blocking epigenetic transition of PPAR?2

    PubMed Central

    Ho Lee, Jun; Hee Lee, Hwan; Jin Ye, Byeong; Lee-Kwon, Whaseon; Youn Choi, Soo; Moo Kwon, Hyug

    2015-01-01

    TonEBP is a key transcription factor in cellular adaptation to hypertonic stress, and also in macrophage activation. Since TonEBP is involved in inflammatory diseases such as rheumatoid arthritis and atherosclerosis, we asked whether TonEBP played a role in adipogenesis and insulin resistance. Here we report that TonEBP suppresses adipogenesis and insulin signaling by inhibiting expression of the key transcription factor PPAR?2. TonEBP binds to the PPAR?2 promoter and blocks the epigenetic transition of the locus which is required for the activation of the promoter. When TonEBP expression is reduced, the epigenetic transition and PPAR?2 expression are markedly increased leading to enhanced adipogenesis and insulin response while inflammation is reduced. Thus, TonEBP is an independent determinant of adipose insulin sensitivity and inflammation. TonEBP is an attractive therapeutic target for insulin resistance in lieu of PPAR? agonists. PMID:26042523

  19. Suppressed Charmed B Decay

    SciTech Connect

    Snoek, Hella Leonie; /Vrije U., Amsterdam

    2011-11-28

    This thesis describes the measurement of the branching fractions of the suppressed charmed B{sup 0} {yields} D{sup (*)-} a{sub 0}{sup +} decays and the non-resonant B{sup 0} {yields} D{sup (*)-} {eta}{pi}{sup +} decays in approximately 230 million {Upsilon}(4S) {yields} B{bar B} events. The data have been collected with the BABAR detector at the PEP-II B factory at the Stanford Linear Accelerator Center in California. Theoretical predictions of the branching fraction of the B{sup 0} {yields} D{sup (*)-} a{sub 0}{sup +} decays show large QCD model dependent uncertainties. Non-factorizing terms, in the naive factorization model, that can be calculated by QCD factorizing models have a large impact on the branching fraction of these decay modes. The predictions of the branching fractions are of the order of 10{sup -6}. The measurement of the branching fraction gives more insight into the theoretical models. In general a better understanding of QCD models will be necessary to conduct weak interaction physics at the next level. The presence of CP violation in electroweak interactions allows the differentiation between matter and antimatter in the laws of physics. In the Standard Model, CP violation is incorporated in the CKM matrix that describes the weak interaction between quarks. Relations amongst the CKM matrix elements are used to present the two relevant parameters as the apex of a triangle (Unitarity Triangle) in a complex plane. The over-constraining of the CKM triangle by experimental measurements is an important test of the Standard Model. At this moment no stringent direct measurements of the CKM angle {gamma}, one of the interior angles of the Unitarity Triangle, are available. The measurement of the angle {gamma} can be performed using the decays of neutral B mesons. The B{sup 0} {yields} D{sup (*)-} a{sub 0}{sup +} decay is sensitive to the angle {gamma} and, in comparison to the current decays that are being employed, could significantly enhance the measurement of this angle. However, the low expected branching fraction for the B{sup 0} {yields} D{sup (*)-} a{sub 0}{sup +} decay channels could severely impact the measurement. A prerequisite of the measurement of the CKM angle is the observation of the B{sup 0} {yields} D{sup (*)-} a{sub 0}{sup +} decay on which this thesis reports. The BABAR experiment consists of the BABAR detector and the PEP-II e{sup +}e{sup -} collider. The design of the experiment has been optimized for the study of CP violation in the decays of neutral B mesons but is also highly suitable for the search for rare B decays such as the B{sup 0} {yields} D{sup (*)-} a{sub 0}{sup +} decay. The PEP-II collider operates at the {Upsilon}(4S) resonance and is a clean source of B{bar B} meson pairs.

  20. Sex-Specific Differences in an ApoE(-/-):Ins2(+/Akita) Mouse Model of Accelerated Atherosclerosis.

    PubMed

    Venegas-Pino, Daniel E; Wang, Pei-Wen; Stoute, Heidi K; Singh-Pickersgill, Nicholas A; Hong, Brian Y; Khan, Mohammad I; Shi, Yuanyuan; Werstuck, Geoff H

    2016-01-01

    Diabetic patients have a twofold to fourfold increased risk of cardiovascular disease. Despite a vast amount of research, the underlying mechanisms that predispose individuals with diabetes to the development of cardiovascular disease are unclear. To further our understanding of how diabetes promotes atherosclerosis, we have established, characterized, and manipulated a new model of hyperglycemia-induced atherosclerosis: the apolipoprotein E-deficient (ApoE(-/-)):Ins2(+/Akita) mouse. All mice were fed a standard chow diet. Male ApoE(-/-):Ins2(+/Akita) mice developed chronic hyperglycemia, which significantly accelerated atherosclerosis. Female ApoE(-/-):Ins2(+/Akita) mice presented hyperglycemia that normalized by 15 weeks of age. Despite the transient hyperglycemia, advanced atherosclerosis was observed at 15 weeks of age compared with ApoE(-/-) females. To better understand these differences, subsets of mice were castrated or ovariectomized at 5 weeks of age. Castrated ApoE(-/-):Ins2(+/Akita) mice showed a reduction in blood glucose levels that correlated with the amelioration of atherosclerosis. Interestingly, castrated normoglycemic ApoE(-/-) mice developed larger atherosclerotic lesions than sham-operated on controls. Ovariectomized ApoE(-/-):Ins2(+/Akita) mice presented chronic hyperglycemia, and atherosclerosis appeared to be advanced. We have characterized the distinctive sex-specific phenotypes exhibited by the ApoE(-/-):Ins2(+/Akita) mouse model and present evidence for the action of sex hormones on pancreatic ?-cell function and the vasculature that affect the regulation of blood glucose levels and the development of atherosclerosis. This model will provide a test bed to further delineate these effects. PMID:26597883

  1. Long-term exposure to traffic-related air pollution and progression of carotid artery atherosclerosis: a prospective cohort study

    PubMed Central

    Gan, Wen Qi; Allen, Ryan W; Brauer, Michael; Davies, Hugh W; Mancini, G B John; Lear, Scott A

    2014-01-01

    Objectives Epidemiological studies have demonstrated associations between long-term exposure to traffic-related air pollution and coronary heart disease (CHD). Atherosclerosis is the principal pathological process responsible for CHD events, but effects of traffic-related air pollution on progression of atherosclerosis are not clear. This study aimed to investigate associations between long-term exposure to traffic-related air pollution and progression of carotid artery atherosclerosis. Setting Healthy volunteers in metropolitan Vancouver, Canada. Participants and outcome measures 509 participants aged 30–65?years were recruited and followed for approximately 5?years. At baseline and end of follow-up, participants underwent carotid artery ultrasound examinations to assess atherosclerosis severity, including carotid intima-media thickness, plaque area, plaque number and total area. Annual change of each atherosclerosis marker during the follow-up period was calculated as the difference between these two measurements divided by years of follow-up. Living close to major roads was defined as ?150?m from a highway or ?50?m from a major road. Residential exposures to traffic-related air pollutants including black carbon, fine particles, nitrogen dioxide and nitric oxide were estimated using high-resolution land-use regression models. The data were analysed using general linear models adjusting for various covariates. Results At baseline, there were no significant differences in any atherosclerosis markers between participants living close to and those living away from major roads. After follow-up, the differences in annual changes of these markers between these two groups were small and not statistically significant. Also, no significant associations were observed with concentrations of traffic-related air pollutants including black carbon, fine particles, nitrogen dioxide and nitric oxide. Conclusions This study did not find significant associations between traffic-related air pollution and progression of carotid artery atherosclerosis in a region with lower levels and smaller contrasts of ambient air pollution. PMID:24710134

  2. Risk of carotid atherosclerosis is associated with low serum paraoxonase (PON1) activity among arsenic exposed residents in Southwestern Taiwan

    SciTech Connect

    Li, W.-F.; Sun, C.-W.; Cheng, T.-J.; Chang, K.-H.; Chen, C.-J.; Wang, S.-L.

    2009-04-15

    To understand whether human paraoxonase 1 (PON1) would modulate the risk for arsenic-related atherosclerosis, we studied 196 residents from an arseniasis-endemic area in Southwestern Taiwan and 291 age- and sex-matched residents from a nearby control area where arsenic exposure was found low. Carotid atherosclerosis was defined by a carotid artery intima-media wall thickness (IMT) of > 1.0 mm. Prevalence of carotid atherosclerosis was increased in the arseniasis-endemic area as compared to the control area after adjustment for conventional risk factors (OR = 2.20, p < 0.01). The prevalence was positively associated with cumulative arsenic exposure (mg/L-year) in a dose-dependent manner. Multiple logistic regression analysis showed that in the endemic group, low serum PON1 activity was an independent risk factor for atherosclerosis (OR = 4.18 low vs. high, p < 0.05). For those of low PON1 activity and high cumulative arsenic exposure, the odds ratio for the prevalence of atherosclerosis was further increased up to 5.68 (p < 0.05). No significant association was found between atherosclerosis and four polymorphisms of the PON gene cluster (PON1 - 108C/T, PON1 Q192R, PON2 A148G, PON2 C311S). However, genetic frequencies of certain alleles including PON1 Q192, PON2 G148 and PON2 C311 were found increased in the endemic group as compared to the controls and a general Chinese population, indicating a possible survival selection in the endemic group after a long arsenic exposure history. Our results showed a significant joint effect between arsenic exposure and serum PON1 activity on carotid atherosclerosis, suggesting that subjects of low PON1 activity may be more susceptible to arsenic-related cardiovascular disease.

  3. Particulate matter components and subclinical atherosclerosis: common approaches to estimating exposure in a Multi-Ethnic Study of Atherosclerosis cross-sectional study

    PubMed Central

    2013-01-01

    Background Concentrations of outdoor fine particulate matter (PM2.5) have been associated with cardiovascular disease. PM2.5 chemical composition may be responsible for effects of exposure to PM2.5. Methods Using data from the Multi-Ethnic Study of Atherosclerosis (MESA) collected in 2000–2002 on 6,256 US adults without clinical cardiovascular disease in six U.S. metropolitan areas, we investigated cross-sectional associations of estimated long-term exposure to total PM2.5 mass and PM2.5 components (elemental carbon [EC], organic carbon [OC], silicon and sulfur) with measures of subclinical atherosclerosis (coronary artery calcium [CAC] and right common carotid intima-media thickness [CIMT]). Community monitors deployed for this study from 2007 to 2008 were used to estimate exposures at baseline addresses using three commonly-used approaches: (1) nearest monitor (the primary approach), (2) inverse-distance monitor weighting and (3) city-wide average. Results Using the exposure estimate based on nearest monitor, in single-pollutant models, increased OC (effect estimate [95% CI] per IQR: 35.1 ?m [26.8, 43.3]), EC (9.6 ?m [3.6,15.7]), sulfur (22.7 ?m [15.0,30.4]) and total PM2.5 (14.7 ?m [9.0,20.5]) but not silicon (5.2 ?m [?9.8,20.1]), were associated with increased CIMT; in two-pollutant models, only the association with OC was robust to control for the other pollutants. Findings were generally consistent across the three exposure estimation approaches. None of the PM measures were positively associated with either the presence or extent of CAC. In sensitivity analyses, effect estimates for OC and silicon were particularly sensitive to control for metropolitan area. Conclusion Employing commonly-used exposure estimation approaches, all of the PM2.5 components considered, except silicon, were associated with increased CIMT, with the evidence being strongest for OC; no component was associated with increased CAC. PM2.5 chemical components, or other features of the sources that produced them, may be important in determining the effect of PM exposure on atherosclerosis. These cross-sectional findings await confirmation in future work employing longitudinal outcome measures and using more sophisticated approaches to estimating exposure. PMID:23641873

  4. An activator of mTOR inhibits oxLDL-induced autophagy and apoptosis in vascular endothelial cells and restricts atherosclerosis in apolipoprotein E?/? mice.

    PubMed

    Peng, Nan; Meng, Ning; Wang, ShengQing; Zhao, Fei; Zhao, Jing; Su, Le; Zhang, ShangLi; Zhang, Yun; Zhao, BaoXiang; Miao, JunYing

    2014-01-01

    Oxidized low-density lipoprotein (oxLDL) inhibits mammalian target of rapamycin (mTOR) and induces autophagy and apoptosis in vascular endothelial cells (VECs) that play very critical roles for the cardiovascular homostasis. We recently defined 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) as a new activator of mTOR. Therefore, we hypothesized that 3BDO had a protective role in VECs and thus stabilized atherosclerotic lesions in apolipoprotein E(-/-) (apoE(-/-)) mice. Our results showed that oxLDL inhibited the activity of mTOR and increased the protein level of autophagy-related 13 (ATG13) and its dephosphorylation, thus inducing autophagy in human umbilical vein endothelial cells (HUVECs). All of these effects were strongly inhibited by 3BDO. In vivo experiments confirmed that 3BDO activated mTOR and decreased the protein level of ATG13 in the plaque endothelium of apoE(-/-) mice. Importantly, 3BDO did not affect the activity of mTOR and autophagy in macrophage cell line RAW246.7 and vascular smooth muscle cells of apoE(-/-) mice, but suppressed plaque endothelial cell death and restricted atherosclerosis development in the mice. 3BDO protected VECs by activating mTOR and thus stabilized atherosclerotic lesions in apoE(-/-) mice. PMID:24980430

  5. An activator of mTOR inhibits oxLDL-induced autophagy and apoptosis in vascular endothelial cells and restricts atherosclerosis in apolipoprotein E-/- mice

    PubMed Central

    Peng, Nan; Meng, Ning; Wang, ShengQing; Zhao, Fei; Zhao, Jing; Su, Le; Zhang, ShangLi; Zhang, Yun; Zhao, BaoXiang; Miao, JunYing

    2014-01-01

    Oxidized low-density lipoprotein (oxLDL) inhibits mammalian target of rapamycin (mTOR) and induces autophagy and apoptosis in vascular endothelial cells (VECs) that play very critical roles for the cardiovascular homostasis. We recently defined 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) as a new activator of mTOR. Therefore, we hypothesized that 3BDO had a protective role in VECs and thus stabilized atherosclerotic lesions in apolipoprotein E-/- (apoE-/-) mice. Our results showed that oxLDL inhibited the activity of mTOR and increased the protein level of autophagy-related 13 (ATG13) and its dephosphorylation, thus inducing autophagy in human umbilical vein endothelial cells (HUVECs). All of these effects were strongly inhibited by 3BDO. In vivo experiments confirmed that 3BDO activated mTOR and decreased the protein level of ATG13 in the plaque endothelium of apoE-/- mice. Importantly, 3BDO did not affect the activity of mTOR and autophagy in macrophage cell line RAW246.7 and vascular smooth muscle cells of apoE-/- mice, but suppressed plaque endothelial cell death and restricted atherosclerosis development in the mice. 3BDO protected VECs by activating mTOR and thus stabilized atherosclerotic lesions in apoE-/- mice. PMID:24980430

  6. 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

  7. Development of atherosclerosis over a 25 year period: an epidemiological autopsy study in males of 11 towns.

    PubMed

    Zhdanov, V S; Sternby, N H; Vikhert, A M; Galakhov, I E

    1999-01-01

    We conducted an analysis of the data from two epidemiological autopsy studies of atherosclerosis in men aged 20-59 years in 1963-66 (the first study, 7470 cases) and in 1985-88 (the second study, 9600 cases). The investigations were performed in accordance with a special program of the World Health Organization in 11 town populations: Ashkhabad (Turkmenistan), Bishkek (Kirgizstan), Irkutsk and Yakutsk (Russia), Malmo (Sweden), Prague (Czech Republic), Riga (Latvia), Tallinn and Tartu (Estonia), and Kharkov and Yalta (Ukraine). Native and non-native populations were studied separately in Ashkhabad, Bishkek, and Yakutsk. Atherosclerosis was studied by the visual morphometrical method in the descending thoracic aorta, abdominal aorta and three main coronary arteries. In each vessel the prevalence and extent (percent of intimal surface) of fatty streaks, fibrous plaques, complicated, calcified and also raised lesions (all lesions except fatty streaks) were determined. Coronary stenosis was estimated in arteries as narrowed by more than 50%. Accelerated development of coronary atherosclerosis, especially in the 40-59 year age group, was noted in the second study in the male populations of most towns except Prague and Malmo. In Prague the extent of raised lesions in coronary arteries was practically the same in both studies, in Malmo it decreased in the second study. Aortic atherosclerosis also accelerated the rate of progression in all towns except Prague, where significant differences were not observed between the studies. Accelerated development of atherosclerosis in male populations from towns of Asia was combined with an increase of fatty streaks in all vessels, while in European populations it was not so obvious. In the native populations of Ashkhabad, Bishkek and Yakutsk, atherosclerosis was much less than in non-natives in both studies. In natives of these towns, accelerated development of atherosclerosis begins only from 40 years, in non-natives from 30. For the second study, there was typically an increase of the prevalence and extent of calcified lesions that were combined with an increased prevalence of coronary stenosis in all towns. The average percentage of stenosis in the coronary left anterior descending artery for men of 40-59 years of age was 12% in the first study and 24.9% in the second; for the coronary right artery, 7.4 and 13.8%, respectively. In accordance with findings of more severe atherosclerosis in males in most towns in the second study, there was an increase in the frequency of death from coronary heart disease in the second study in these towns. The data of this study indicate that the development of atherosclerosis in human populations may change very much in the course of the life of one generation. PMID:10077406

  8. Very low levels of HDL cholesterol and atherosclerosis, a variable relationship--a review of LCAT deficiency.

    PubMed

    Savel, Julia; Lafitte, Marianne; Pucheu, Yann; Pradeau, Vincent; Tabarin, Antoine; Couffinhal, Thierry

    2012-01-01

    A number of epidemiological and clinical studies have demonstrated that plasma high-density lipoprotein (HDL) level is a strong inverse predictor of cardiovascular events. HDL is believed to retard the formation of atherosclerotic lesions by removing excess cholesterol from cells and preventing endothelial dysfunction. Lecithin cholesterol acyltransferase (LCAT) plays a central role in the formation and maturation of HDL, and in the intravascular stage of reverse cholesterol transport: a major mechanism by which HDL modulates the development and progression of atherosclerosis. A defect in LCAT function would be expected to enhance atherosclerosis, by interfering with the reverse cholesterol transport step. As such, one would expect to find more atherosclerosis and cardiovascular events in LCAT-deficient patients. But this relationship is not always evident. In this review, we describe contradictory reports in the literature about cardiovascular risks in this patient population. We discuss the paradoxical finding of severe HDL deficiency and an absence of subclinical atherosclerosis in LCAT-deficient patients, which has been used to reject the hypothesis that HDL level is important in the protection against atherosclerosis. Furthermore, to illustrate this paradoxical finding, we present a case study of one patient, referred for evaluation of global cardiovascular risk in the presence of a low HDL cholesterol level, who was diagnosed with LCAT gene mutations. PMID:22701329

  9. Soft substrates suppress droplet splashing

    E-print Network

    Howland, Christopher J; Style, Robert W; Castrejón-Pita, A A

    2015-01-01

    Droplets splash when they impact dry, flat substrates above a critical velocity that depends on parameters such as droplet size, viscosity and air pressure. We show that substrate stiffness also impacts the splashing threshold by imaging ethanol drops impacting silicone gels of different stiffnesses. Splashing is significantly suppressed: droplets on the softest substrates need over 70% more kinetic energy to splash than they do on rigid substrates. We show that splash suppression is likely to be due to energy losses caused by deformations of soft substrates during the first few microseconds of impact. We find that solids with Youngs modulus $\\lesssim O(10^5)$Pa suppress splashing, in agreement with simple scaling arguments. Thus materials like soft gels and elastomers can be used as simple coatings for effective splash prevention.

  10. Vibration suppression using smart structures

    NASA Technical Reports Server (NTRS)

    Garcia, Ephrahim; Inman, Daniel J.; Dosch, Jeffrey

    1991-01-01

    The control of structures for vibration suppression is discussed in the context of using smart materials and structures. Here the use of smart structures refers to using embedded piezoelectric devices as both control actuators and sensors. Using embedded sensors and actuators allows great improvements in performance over traditional structures (both passive and active) for vibration suppression. The application of smart structures to three experimental flexible structures is presented. The first is a flexible beam, the second is a flexible beam undergoing slewing motion, the third is a ribbed antenna. A simple model of a piezoelectric actuator/sensor is presented. The equations of motion for each structure is presented. The control issues considered as those associated with multi-input, multi-output control, PID control and LQR control implementation. A modern control analysis illustrates the usefulness of smart structures for vibration suppression.

  11. Danhong injection inhibits the development of atherosclerosis in both Apoe?/? and Ldlr?/? mice.

    PubMed

    Chen, Yuanli; Liu, Mengyang; Zhao, Tao; Zhao, Buchang; Jia, Lifu; Zhu, Yan; Zhang, Boli; Gao, Xiumei; Li, Guangliang; Li, Xiaoju; Xiang, Rong; Han, Jihong; Duan, Yajun

    2014-05-01

    Danhong injection (DHI), a certificated Chinese medical product made from radix salviae miltiorrhizae and flos carthami, is prescribed to patients with coronary heart disease in China. To investigate if DHI can inhibit atherosclerosis, apolipoprotein E-deficient (Apoe?/?) or low-density lipoprotein receptor-deficient (Ldlr?/?) mice on high-fat diet were divided into 2 groups and received daily intraperitoneal injection of saline and DHI, respectively, for 16 or 20 weeks. After the treatment, mouse aortas were collected to determine lesions, expression of adenosine triphosphate-binding cassette transporter A1 and tumor necrosis factor-? (TNF-?), and macrophage accumulation. Additionally, serum lipid profiles and expression of hepatic HMG-CoA reductase messenger RNA and low-density lipoprotein receptor protein were determined. We observed that DHI inhibited lesions in both Apoe?/? and Ldlr?/? mice. Associated with the decreased lesions, the aortic adenosine triphosphate-binding cassette transporter A1 expression was increased, whereas the macrophage accumulation was decreased in male Apoe?/? mice and both male and female Ldlr?/? mice. Although DHI reduced HMG-CoA reductase messenger RNA expression in both female Apoe?/? and Ldlr?/? mice, it decreased low-density lipoprotein cholesterol levels only in female Apoe?/? mice. In addition to attenuation of lipopolysaccharide-induced expression of TNF-?, IL-1?, IL-6 in macrophages, and human C-reactive protein in hepatocytes, respectively, at the transcriptional level in vitro, DHI also reduced TNF-? protein expression in aortic root of both Apoe?/? and Ldlr?/? mice, suggesting the importance of the anti-inflammatory properties of DHI in the inhibition of lesion development. Taken together, our study demonstrates that DHI inhibits atherosclerosis in both Apoe?/? and Ldlr?/? mice with various mechanisms, including anti-inflammation. The inhibition of atherosclerosis can be attributed to the cardioprotective properties of DHI. PMID:24803317

  12. The importance of indicators of the initial phase of atherosclerosis in patients with microvascular angina.

    PubMed

    Scudlová, Marie; Skvarilová, Marcela; Bulava, Alan

    2003-12-01

    Endothelial dysfunction (ED) is generally considered to be the initial step in the progression to atherosclerosis but there is still much uncertainty about the role of the microvascular form of angina in patients with a normal coronary angiogram with regard to ED. The authors investigated the extent of endothelial perturbation and thereby whether the microvascular form of angina precedens macroscopic atherosclerosis by means of non-invasive ultrasound measurement of the intima-media thickening (IMT) in common carotid artery and flow mediated dilatation (FMD) in the brachial artery. 28 patients with stable angina with positive exercise test and ST segment depression (22 females, 6 males, average age 54 years) were compared with a control group consisting of 28 patients with no clinical signs of coronary artery disease (18 females, 10 males, average age 53 years). No significant difference in FMD% (7.3 vs. 10.8, p = 0.07) was found between the groups, though specific measurements (average dilatation of the brachial artery induced by ischemic insult, peak blood flow and peak hyperemic flow) differed considerably. Also IMT did not vary significantly between the groups (0.74 vs. 0.65, p = 0.08). In patients with IMT > 0.8 mm (6 patients in each group) a significant decrease of FMD was found as compared with patients with normal IMT (p < 0.05). It was concluded that in patients with increased IMT an inverse relationship between FMD and IMT exists both in patients with microvascular angina and in the healthy control subjects whereas in the group of patients with normal IMT no ED was demonstrated. This supports the hypothesis that the microvascular form of angina is the early stage of coronary artery atherosclerosis and this escapes angiographic recognition. PMID:15037906

  13. Association between various anthropometric measures of obesity and markers of subclinical atherosclerosis.

    PubMed

    Kommuri, Naga Va; Zalawadiya, Sandip K; Veeranna, Vikas; Kollepara, Sri Lakshmi S; Ramesh, Krithi; Briasoulis, Alexandros; Afonso, Luis

    2016-01-01

    Central obesity is a known cardiovascular risk factor and measures of visceral obesity are known to predict atherosclerosis. This study sought to explore the association between various anthropometric measures and markers of subclinical atherosclerosis (MoSCA) among low risk healthy individuals. Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of Caucasian (38%), Afro-American (28%), Chinese (22%) and Hispanic (12%) subjects, aged 45-84 years, free from clinical cardiovascular disease. We performed a post hoc analysis of the limited access dataset of MESA subjects to evaluate the association between carotid intima media thickness and coronary artery calcium score (CACS), as MoSCA and various measures of obesity. Multivariable regression analyses adjusted for traditional cardiovascular risk factors, ethnicity and C-reactive protein were performed. Each unit increase in waist-hip ratio was strongly associated with increase in both common and internal carotid intima media thickness (beta: 0.12, 95% confidence interval (CI): 0.06 to 0.18, p < 0.001 and beta: 0.23, 95% CI: 0.03 to 0.43, p = 0.021, respectively). Measures of central obesity were superior to body mass index as demonstrated by their consistent association with each category of CACS when compared to the reference category (CACS = 0). Compared to body mass index, measures of visceral obesity were significantly associated with MoSCA in this multiethnic healthy population. Waist-hip ratio seems to be more consistent in its association with various MoSCA compared to other anthropometric measures. PMID:26559851

  14. Interaction of workplace demands and cardiovascular reactivity in progression of carotid atherosclerosis: population based study.

    PubMed Central

    Everson, S. A.; Lynch, J. W.; Chesney, M. A.; Kaplan, G. A.; Goldberg, D. E.; Shade, S. B.; Cohen, R. D.; Salonen, R.; Salonen, J. T.

    1997-01-01

    OBJECTIVE: To examine the combined influence of workplace demands and changes in blood pressure induced by stress on the progression of carotid atherosclerosis. DESIGN: Population based follow up study of unestablished as well as traditional risk factors for carotid atherosclerosis, ischaemic heart disease, and other outcomes. SETTING: Eastern Finland. SUBJECTS: 591 men aged 42-60 who were fully employed at baseline and had complete data on the measures of carotid atherosclerosis, job demands, blood pressure reactivity, and covariates. MAIN OUTCOME MEASURES: Change in ultrasonographically assessed intima-media thickness of the right and left common carotid arteries from baseline to 4 year follow up. RESULTS: Significant interactions between workplace demands and stress induced reactivity were observed for all measures of progression (P < 0.04). Men with large changes in systolic blood pressure (20 mm Hg or greater) in anticipation of a maximal exercise test and with high job demands had 10-40% greater progression of mean (0.138 v 0.123 mm) and maximum (0.320 v 0.261 mm) intima-media thickness and plaque height (0.347 v 0.264) than men who were less reactive and had fewer job demands. Similar results were obtained after excluding men with prevalent ischaemic heart disease at baseline. Findings were strongest among men with at least 20% stenosis or non-stenotic plaque at baseline. In this subgroup reactive men with high job demands had more than 46% greater atherosclerotic progression than the others. Adjustment for atherosclerotic risk factors did not alter the results. CONCLUSIONS: Men who showed stress induced blood pressure reactivity and who reported high job demands experienced the greatest atherosclerotic progression, showing the association between dispositional risk characteristics and contextual determinants of disease and suggesting that behaviourally evoked cardiovascular reactivity may have a role in atherogenesis. PMID:9055713

  15. The pathogenesis of atherosclerosis and new opportunities for treatment and prevention.

    PubMed

    Scott, J

    2002-01-01

    Atherosclerosis is the most common disease in the industrialised world and by 2020 is predicted to be the number 1 cause of death worldwide. It is a disease of the intima and media of small to medium sized arteries that develop slowly over many years. A number of risk factors for atherosclerosis have been identified, some of these are reversible and some are not. Most prominent amongst these is an elevated level of plasma cholesterol. The lowering of cholesterol reduces the risk of heart attacks, strokes and all forms of atherosclerotic vascular disease. Nonetheless, 70% of patients go on to get symptomatic disease. The disease process sets off an inflammatory response involving the vascular endothelium and both T and B cells of the immune system. Adhesion molecules are induced and proinflammatory cytokines and growth factors are produced by cells that orchestrate the atherosclerotic process. Narrowing the lumen of the artery leads to ischaemic symptoms. Within lesions under the influence of proteolytic enzymes released from activated macrophages (or foam cells--the hallmark of atherosclerosis) the centre of the plaque becomes liquefied to take on it's characteristic "gruel" like appearance. The shoulders of such plaque weaken and it becomes prone to rupture. Plaque rupture may lead to catastrophic thrombosis of coronary or cerebral arteries. The large amounts of tissue factor produced by macrophages make this a particularly likely event. On ulcerated plaques adherent platelets and thrombus create showers of emboli leading to ischaemic attacks. Like the effective treatment of LDL and it's role in the prevention of ischaemic attacks there has been a move to develop new drugs that raise HDL. The discovery of the role of a new class of ABC transporter, defective in Tangiers disease, responsible for cholesterol efflux from peripheral cells including the macrophage has created great excitement around ABC1 as a drug target. New areas, new possible targets and new genetic and genomic approaches will be discussed. PMID:12597606

  16. Insights into the antiatherogenic molecular mechanisms of andrographolide against Porphyromonas gingivalis-induced atherosclerosis in rabbits.

    PubMed

    Al Batran, Rami; Al-Bayaty, Fouad; Al-Obaidi, Mazen M Jamil; Ashrafi, Amer

    2014-12-01

    Atherosclerosis is the commonest and most important vascular disease. Andrographolide (AND) is the main bioactive component of the medicinal plant Andrographis paniculata and is used in traditional medicine. This study was aimed to evaluate the antiatherogenic effect of AND against atherosclerosis induced by Porphyromonas gingivalis in White New Zealand rabbits. Thirty rabbits were divided into five groups as follows: G1, normal group; G2-5, were orally challenged with P. gingivalis five times a week over 12 weeks; G2, atherogenic control group; G3, standard group treated with atorvastatin (AV) 5 mg/kg; and G4 and G5, treatment groups treated with AND 10 and 20 mg/kg, respectively over 12 weeks. Serums were subjected to antioxidant enzymatic and anti-inflammatory activities, and the aorta was subjected to histological analyses. Groups treated with AND showed a significant reversal of liver and renal biochemical changes, compared with the atherogenic control group. In the same groups, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total glutathione (GSH) levels in serum were significantly increased (P < 0.05), and lipid peroxidation (malondialdehyde (MDA)) levels were significantly decreased (P < 0.05), respectively. Furthermore, treated groups with AV and AND showed significant decrease in the level of VCAM-1 and ICAM-1 compared with the atherogenic control group. In aortic homogenate, the level of nitrotyrosine was significantly increased, while the level of MCP1 was significantly decreased in AV and AND groups compared with the atherogenic control group. In addition, staining the aorta with Sudan IV showed a reduction in intimal thickening plaque in AV and AND groups compared with the atherogenic control group. AND has showed an antiatherogenic property as well as the capability to reduce lipid, liver, and kidney biomarkers in atherogenic serum that prevents atherosclerosis complications caused by P. gingivalis. PMID:25172523

  17. Heart-Carotid Pulse Wave Velocity a Useful Index of Atherosclerosis in Chinese Hypertensive Patients

    PubMed Central

    Li, Chunyue; Xiong, Huahua; Pirbhulal, Sandeep; Wu, Dan; Li, Zhenzhou; Huang, Wenhua; Zhang, Heye; Wu, Wanqing

    2015-01-01

    Abstract This study was designed to investigate the relationship between heart-carotid pulse wave velocity (hcPWV) and carotid intima-media thickness (CIMT) in hypertensive patients, and also to examine the effect of pre-ejection period (PEP) on it. Doppler ultrasound device was used to measure CIMT in left common carotid artery. Hypertensive patients were divided into normal (n?=?36, CIMT ?0.8?mm) and thickened (n?=?31, CIMT?>?0.8?mm) group. Electrocardiogram R-wave-based carotid pulse wave velocity (rcPWV) and aortic valve-carotid pulse wave velocity (acPWV) were calculated as the ratio of the travel length to the pulse transit time with or without PEP, respectively. CIMT has significant relations with rcPWV (r?=?0.611, P?atherosclerosis, our results suggested that both rcPWV and acPWV could be useful indexes of atherosclerosis in thickened CIMT hypertensive patients. Additionally, if hcPWV is computed with heart-carotid pulse transit time, including PEP could improve the accuracy of atherosclerosis assessment in hypertensive patients. PMID:26705228

  18. Heart-Carotid Pulse Wave Velocity a Useful Index of Atherosclerosis in Chinese Hypertensive Patients.

    PubMed

    Li, Chunyue; Xiong, Huahua; Pirbhulal, Sandeep; Wu, Dan; Li, Zhenzhou; Huang, Wenhua; Zhang, Heye; Wu, Wanqing

    2015-12-01

    This study was designed to investigate the relationship between heart-carotid pulse wave velocity (hcPWV) and carotid intima-media thickness (CIMT) in hypertensive patients, and also to examine the effect of pre-ejection period (PEP) on it. Doppler ultrasound device was used to measure CIMT in left common carotid artery. Hypertensive patients were divided into normal (n?=?36, CIMT ?0.8?mm) and thickened (n?=?31, CIMT?>?0.8?mm) group. Electrocardiogram R-wave-based carotid pulse wave velocity (rcPWV) and aortic valve-carotid pulse wave velocity (acPWV) were calculated as the ratio of the travel length to the pulse transit time with or without PEP, respectively. CIMT has significant relations with rcPWV (r?=?0.611, P?atherosclerosis, our results suggested that both rcPWV and acPWV could be useful indexes of atherosclerosis in thickened CIMT hypertensive patients. Additionally, if hcPWV is computed with heart-carotid pulse transit time, including PEP could improve the accuracy of atherosclerosis assessment in hypertensive patients. PMID:26705228

  19. Graphical modeling of gene expression in monocytes suggests molecular mechanisms explaining increased atherosclerosis in smokers.

    PubMed

    Verdugo, Ricardo A; Zeller, Tanja; Rotival, Maxime; Wild, Philipp S; Münzel, Thomas; Lackner, Karl J; Weidmann, Henri; Ninio, Ewa; Trégouët, David-Alexandre; Cambien, François; Blankenberg, Stefan; Tiret, Laurence

    2013-01-01

    Smoking is a risk factor for atherosclerosis with reported widespread effects on gene expression in circulating blood cells. We hypothesized that a molecular signature mediating the relation between smoking and atherosclerosis may be found in the transcriptome of circulating monocytes. Genome-wide expression profiles and counts of atherosclerotic plaques in carotid arteries were collected in 248 smokers and 688 non-smokers from the general population. Patterns of co-expressed genes were identified by Independent Component Analysis (ICA) and network structure of the pattern-specific gene modules was inferred by the PC-algorithm. A likelihood-based causality test was implemented to select patterns that fit models containing a path "smoking?gene expression?plaques". Robustness of the causal inference was assessed by bootstrapping. At a FDR ?0.10, 3,368 genes were associated to smoking or plaques, of which 93% were associated to smoking only. SASH1 showed the strongest association to smoking and PPARG the strongest association to plaques. Twenty-nine gene patterns were identified by ICA. Modules containing SASH1 and PPARG did not show evidence for the "smoking?gene expression?plaques" causality model. Conversely, three modules had good support for causal effects and exhibited a network topology consistent with gene expression mediating the relation between smoking and plaques. The network with the strongest support for causal effects was connected to plaques through SLC39A8, a gene with known association to HDL-cholesterol and cellular uptake of cadmium from tobacco, while smoking was directly connected to GAS6, a gene reported to have anti-inflammatory effects in atherosclerosis and to be up-regulated in the placenta of women smoking during pregnancy. Our analysis of the transcriptome of monocytes recovered genes relevant for association to smoking and atherosclerosis, and connected genes that before, were only studied in separate contexts. Inspection of correlation structure revealed candidates that would be missed by expression-phenotype association analysis alone. PMID:23372645

  20. Macrophage-Specific Lipid-Based Nanoparticles Improve MRI Detection and Characterization of Human Atherosclerosis

    PubMed Central

    Lipinski, Michael J.; Frias, Juan C.; Amirbekian, Vardan; Briley-Saebo, Karen C.; Mani, Venkatesh; Samber, Daniel; Abbate, Antonio; Aguinaldo, Juan Gilberto S.; Massey, Davis; Fuster, Valentin; Vetrovec, George W.; Fayad, Zahi A.

    2009-01-01

    Objectives We sought to determine if gadolinium (Gd)-containing lipid-based nanoparticles (NPs) targeting the macrophage scavenger receptor-B (CD36) improve magnetic resonance (MR) detection and characterization of human atherosclerosis. Background The ability to detect atherosclerosis with MR imaging using gadolinium Gd-containing lipid-based NPs targeting macrophages may enable early detection of high-risk lesions prior to an atherothrombotic event. Gd-containing lipid-based NPs targeting macrophages improved MR detection of murine atherosclerosis. Methods Gd-containing NPs, anti-CD36 NPs and Fc-NPs were created. Macrophages were incubated with fluorescent targeted and non-targeted NPs to determine uptake via confocal microscopy and inductively coupled plasma mass spectroscopy (ICP-MS) quatified Gd uptake. Human aortic specimens were harvested at autopsy. Using a 1.5 T scanner, T1, T2, and PDW 3-dimensional scans were performed along with post-contrast scans after 24 h incubation. T1 and cluster analysis were performed and compared with immunohistopathology. Results The NPs had a mean diameter of 125 nm, 14,900 Gd-ions, and relaxivity was 37 mM-1s-1 at 1.5T and 37°C. Confocal microscopy and ICP-MS demonstrated significant in vitro macrophage uptake of targeted NPs while non-targeted NPs had minimal uptake. On T1 imaging, targeted NPs increased CNR by 52.5% which was significantly great than Fc-NPs (CNR increased 17.2%) and non-targeted NPs (CNR increased 18.7%) (p=0.001). Confocal fluorescent microscopy showed that NPs target resident macrophages while the untargeted NPs and Fc-NPs are found diffusely throughout the plaque. Targeted NPs had a greater signal intensity increase in the fibrous cap compared with (p<0.001) while non-targeted NPs and Fc-NPs had a greater increase in the lipid core (p<0.01). Conclusion Macrophage-specific (CD36) NPs bind human macrophages and improved MR detection and characterization of human aortic atherosclerosis. Thus, macrophage-specific NPs could help identify high-risk human plaque prior to the development of an atherothrombotic event. PMID:19442953

  1. Role of gut microbiota in the modulation of atherosclerosis-associated immune response

    PubMed Central

    Chistiakov, Dmitry A.; Bobryshev, Yuri V.; Kozarov, Emil; Sobenin, Igor A.; Orekhov, Alexander N.

    2015-01-01

    Inflammation and metabolic abnormalities are linked to each other. At present, pathogenic inflammatory response was recognized as a major player in metabolic diseases. In humans, intestinal microflora could significantly influence the development of metabolic diseases including atherosclerosis. Commensal bacteria were shown to activate inflammatory pathways through altering lipid metabolism in adipocytes, macrophages, and vascular cells, inducing insulin resistance, and producing trimethylamine-N-oxide. However, gut microbiota could also play the atheroprotective role associated with anthocyanin metabolism and administration of probiotics and their components. Here, we review the mechanisms by which the gut microbiota may influence atherogenesis. PMID:26175728

  2. Preliminary report: genetic variation in the human stromelysin promoter is associated with progression of coronary atherosclerosis.

    PubMed Central

    Ye, S.; Watts, G. F.; Mandalia, S.; Humphries, S. E.; Henney, A. M.

    1995-01-01

    Stromelysin is a member of the family of metalloproteinases that degrade extracellular matrix. In situ hybridisation and histopathological studies suggest that stromelysin activity may be important in the connective tissue remodelling processes associated with atherogenesis and plaque rupture. Single strand conformation polymorphism analysis identified a common polymorphism in the stromelysin gene promoter located 1171 bp upstream from the start of transcription in which one allele has a run of six adenosines (6A) and another has five adenosines (5A). 72 men with coronary heart disease, were genotyped. They were participants in the St Thomas' Atherosclerosis Regression Study who were randomised to receive usual care (UC), dietary intervention (D), or diet plus cholestyramine (DC), with angiography at baseline and at 39 months. In these patients the frequency of the 5A allele was 0.49 (95% CI from 0.41 to 0.57) and was not significantly different from that in a sample of 354 healthy UK men. In the UC group, patients who were homozygous for the 6A allele showed greater progression of angiographic disease than those with other genotypes: the minimum absolute width of coronary segments decreased by 0.04 (SEM 0.10) mm for 5A5A, 0.20 (0.07) mm for 5A6A, and 0.67 (0.19) mm for 6A6A (P < 0.01). The findings were similar but slightly less significant for the change in mean absolute width of coronary segments (P < 0.05). No significant associations were seen in patients in the D or DC groups. In data pooled from the three treatment groups, the 6A6A genotype was significantly associated with greater progression of coronary atherosclerosis than other genotypes in patients with baseline percentage diameter stenosis less than 20% (P < 0.05), but not in those with baseline percentage diameter stenosis greater than or equal to 20%. These results provide the first evidence of a link between genetic variation in stromelysin and progression of coronary atherosclerosis and support the hypothesis that connective tissue remodeling mediated by metalloproteinases contribute to the pathogenesis of atherosclerosis. Images PMID:7727178

  3. Molecules that Mimic Apolipoprotein A-I: Potential Agents for Treating Atherosclerosis

    PubMed Central

    Leman, Luke J.; Maryanoff, Bruce E.; Ghadiri, M. Reza

    2013-01-01

    Certain amphipathic ?-helical peptides can functionally mimic many of the properties of full-length apolipoproteins, thereby offering an approach to modulate high-density lipoprotein (HDL) for combating atherosclerosis. In this Perspective, we summarize the key findings and advances over the past 25 years in the development of peptides that mimic apolipoproteins, especially apolipoprotein A-I (apoA-I). This assemblage of information provides a reasonably clear picture of the state of the art in the apolipoprotein mimetic field, an appreciation of the potential for such agents in pharmacotherapy, and a sense of the opportunities for optimizing the functional properties of HDL. PMID:24168751

  4. Some atherosclerosis may be a consequence of the normal adaptive vascular response to shear.

    PubMed

    Friedman, M H

    1990-06-01

    Estimates and measurements of fluid dynamic shear at the arterial wall suggest the presence of mechanisms to regulate this quantity. Arterial wall thickening prompted by chronic reductions in wall shear is one mechanism by which that regulation might be accomplished. Reduced wall shears that are a direct consequence of arterial geometry would be less susceptible to this mechanism, leading to exaggerated and focal intimal thickening, possibly leading to atherosclerosis, at affected sites. Thus some foci of vascular disease can be a natural, if undesirable, consequence of fluid shear regulation. PMID:2375784

  5. Early and Long-Term Results of Subclavian Angioplasty in Aortoarteritis (Takayasu Disease): Comparison with Atherosclerosis

    SciTech Connect

    Tyagi, Sanjay; Verma, Puneet K.; Gambhir, Daljeet S.; Kaul, Upkar A.; Saha, Renuka; Arora, Ramesh

    1998-05-15

    Purpose: To compare the early andlong-term outcomes of subclavian artery angioplasty in patients with aortoarteritis and atherosclerosis. Methods: Sixty-one subclavian artery angioplasties were performed in 55 consecutive patients with aortoarteritis (n= 32) and atherosclerosis (n= 23) between 1986 and 1995. An arch aortogram followed by a selective subclavian artery angiogram was done to profile the site and extent of the lesion, its relation to the vertebral artery, and the distal circulation. Percutaneous transluminal angioplasty (PTA) was performed via the femoral route for 56 stenotic lesions and 5 total occlusions. Results: PTA was successful in 52 (92.8%) stenotic lesions and 3 (60%) total occlusions. Three patients (5.4%) had complications, that could be effectively managed nonsurgically. Compared with atherosclerosis, patients with aortoarteritis were younger (27.4 {+-} 9.3 years vs 54.5 {+-} 10.5 years; p < 0.001), more often female (75% vs 17.4%; p < 0.001), gangrene was uncommon (0% vs 17.4%; p < 0.05), and diffuse involvement was seen more often (43.8% vs 4.4%; p < 0.001). The luminal diameter stenoses were similar before PTA (88.6 {+-} 9.7% vs 89.0 {+-} 9.1%; p= NS). Higher balloon inflation pressure was required to dilate the lesions of aortoarteritis (9.9 {+-} 4.6 ATM vs 5.5 {+-} 1.0 ATM; p < 0.001). This group had more residual stenosis (15.5 {+-} 12.4% vs 8.3 {+-} 9.4%; p < 0.05) after PTA. There were no neurological sequelae, even in PTA of prevertebral lesions. On 3-120 months (mean 43.3 {+-} 28.9 months) follow-up of 40 patients, restenosis was more often observed in patients with aortoarteritis, particularly in those with diffuse arterial narrowing. These lesions could be effectively redilated. Clinical symptoms showed marked improvement after successful angioplasty. Conclusion: Subclavian PTA is safe and can be performed as effectively in aortoarteritis as in atherosclerosis, with good long-term results. Long-term follow-up shows that it provides good symptomatic relief.

  6. 18FDG PET-CT imaging detects arterial inflammation and early atherosclerosis in HIV-infected adults with cardiovascular disease risk factors

    PubMed Central

    2012-01-01

    Background Persistent vascular inflammation has been implicated as an important cause for a higher prevalence of cardiovascular disease (CVD) in HIV-infected adults. In several populations at high risk for CVD, vascular 18Fluorodeoxyglucose (18FDG) uptake quantified using 3D-positron emission-computed tomography (PET-CT) has been used as a molecular level biomarker for the presence of metabolically active proinflammatory macrophages in rupture-prone early atherosclerotic plaques. We hypothesized that 18FDG PET-CT imaging would detect arterial inflammation and early atherosclerosis in HIV-infected adults with modest CVD risk. Methods We studied 9 HIV-infected participants with fully suppressed HIV viremia on antiretroviral therapy (8 men, median age 52?yrs, median BMI 29?kg/m2, median CD4 count 655 cells/?L, 33% current smokers) and 5 HIV-negative participants (4 men, median age 44?yrs, median BMI 25?kg/m2, no current smokers). Mean Framingham Risk Scores were higher for HIV-infected persons (9% vs. 2%, p?atherosclerosis between HIV-infected adults with CVD risk factors and healthy HIV-seronegative controls. These findings confirm the utility of this molecular level imaging approach for detecting and quantifying glucose uptake into inflammatory macrophages present in metabolically active, rupture-prone atherosclerotic plaques in HIV infected adults; a population with increased CVD risk. PMID:22726233

  7. Anatomical Confirmation of Computed Tomography-Based Diagnosis of the Atherosclerosis Discovered in 17th Century Korean Mummy

    PubMed Central

    Kim, Myeung Ju; Kim, Yi-Suk; Oh, Chang Seok; Go, Jai-Hyang; Lee, In Sun; Park, Won-Kyu; Cho, Seok-Min; Kim, Soon-Kwan; Shin, Dong Hoon

    2015-01-01

    In the present study on a newly discovered 17th century Korean mummy, computed tomography (CT) revealed multiple aortic calcifications within the aortic wall that were indicative of ancient atherosclerosis. The CT-based findings were confirmed by our subsequent post-factum dissection, which exhibited possible signs of the disease including ulcerated plaques, ruptured hemorrhages, and intimal thickening where the necrotic core was covered by the fibrous cap. These findings are strong indicators that the mummy suffered from aortic atherosclerosis during her lifetime. The present study is a good example of how CT images of vascular calcifications can be a useful diagnostic tool in forming at least preliminary diagnoses of ancient atherosclerosis. PMID:25816014

  8. Non-invasive Detection of Aortic and Coronary Atherosclerosis in Homozygous Familial Hypercholesterolemia by 64 Slice Multi-detector Row Computed Tomography Angiography

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by the early onset of atherosclerosis, often at the ostia of coronary arteries. In this study we document for the first time that aortic and coronary atherosclerosis can be detected using 64 slice multiple detector-row ...

  9. Non-invasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multi-detector row computed tomography angiography

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by the early onset of atherosclerosis, often at the ostia of coronary arteries. In this study we document for the first time that aortic and coronary atherosclerosis can be detected using 64 slice multiple detector row ...

  10. Aortic Distensibility and its Relationship to Coronary and Thoracic Atherosclerosis Plaque and Morphology by MDCT: Insights from the ROMICAT Trial

    PubMed Central

    Siegel, Emily; Thai, Wai-Ee; Techasith, Tust; Major, Gyongyi; Szymonifka, Jackie; Tawakol, Ahmed; Nagurney, John T.; Hoffmann, Udo; Truong, Quynh A.

    2012-01-01

    Background Multi-detector cardiac computed tomography (CT) allows for simultaneous assessment of aortic distensibility (AD), coronary atherosclerosis, and thoracic aortic atherosclerosis. Objectives We sought to determine the relationship of AD to the presence and morphological features in coronary and thoracic atherosclerosis. Methods In 293 patients (53±12 years, 63% male), retrospectively-gated MDCT were performed. We measured intraluminal aortic areas across 10 phases of the cardiac cycle (multiphase reformation 10% increments) at pre-defined locations to calculate the ascending, descending, and local AD (at locations of thoracic plaque). AD was calculated as maximum change in area/(minimum area × pulse pressure). Coronary and thoracic plaques were categorized as calcified, mixed, or non-calcified. Results Ascending and descending AD were lower in patients with any coronary plaque, calcified or mixed plaque than those without (all p<0.0001) but not with non-calcified coronary plaque (p?0.46). Per 1 mmHg?110?3 increase in ascending and descending AD, there was an 18–29% adjusted risk reduction for having any coronary, calcified plaque, or mixed coronary plaque (ascending AD only) (all p?0.04). AD was not associated with non-calcified coronary plaque or when age was added to the models (all p>0.39). Local AD was lower at locations of calcified and mixed thoracic plaque when compared to non-calcified thoracic atherosclerosis (p<0.04). Conclusions A stiffer, less distensible aorta is associated with coronary and thoracic atherosclerosis, particularly in the presence of calcified and mixed plaques, suggesting that the mechanism of atherosclerosis in small and large vessels is similar and influenced by advancing age. PMID:22578738

  11. Endothelial Hypoxia-Inducible Factor-1? Promotes Atherosclerosis and Monocyte Recruitment by Upregulating MicroRNA-19a.

    PubMed

    Akhtar, Shamima; Hartmann, Petra; Karshovska, Ela; Rinderknecht, Fatuma-Ayaan; Subramanian, Pallavi; Gremse, Felix; Grommes, Jochen; Jacobs, Michael; Kiessling, Fabian; Weber, Christian; Steffens, Sabine; Schober, Andreas

    2015-12-01

    Chemokines mediate monocyte adhesion to dysfunctional endothelial cells (ECs) and promote arterial inflammation during atherosclerosis. Hypoxia-inducible factor (HIF)-1? is expressed in various cell types of atherosclerotic lesions and is associated with lesional inflammation. However, the impact of endothelial HIF-1? in atherosclerosis is unclear. HIF-1? was detectable in the nucleus of ECs covering murine and human atherosclerotic lesions. To study the role of endothelial HIF-1? in atherosclerosis, deletion of the Hif1a gene was induced in ECs from apolipoprotein E knockout mice (EC-Hif1a(-/-)) by Tamoxifen injection. The formation of atherosclerotic lesions, the lesional macrophage accumulation, and the expression of CXCL1 in ECs were reduced after partial carotid ligation in EC-Hif1a(-/-) compared with control mice. Moreover, the lesion area and the lesional macrophage accumulation were decreased in the aortas of EC-Hif1a(-/-) mice compared with control mice during diet-induced atherosclerosis. In vitro, mildly oxidized low-density lipoprotein or lysophosphatidic acid 20:4 increased endothelial CXCL1 expression and monocyte adhesion by inducing HIF-1? expression. Moreover, endothelial Hif1a deficiency resulted in downregulation of miR-19a in atherosclerotic arteries determined by microRNA profiling. In vitro, HIF-1?-induced miR-19a expression mediated the upregulation of CXCL1 in mildly oxidized low-density lipoprotein-stimulated ECs. These results indicate that hyperlipidemia upregulates HIF-1? expression in ECs by mildly oxidized low-density lipoprotein-derived unsaturated lysophosphatidic acid. Endothelial HIF-1? promoted atherosclerosis by triggering miR-19a-mediated CXCL1 expression and monocyte adhesion, indicating that inhibition of the endothelial HIF-1?/miR-19a pathway may be a therapeutic option against atherosclerosis. PMID:26483345

  12. SR-BI in bone marrow derived cells protects mice from diet induced coronary artery atherosclerosis and myocardial infarction.

    PubMed

    Pei, Ying; Chen, Xing; Aboutouk, Dina; Fuller, Mark T; Dadoo, Omid; Yu, Pei; White, Elizabeth J; Igdoura, Suleiman A; Trigatti, Bernardo L

    2013-01-01

    SR-BI deficient mice that are also hypomorphic for apolipoprotein E expression develop diet induced occlusive coronary artery atherosclerosis, myocardial infarction and early death. To test the role of SR-BI in bone marrow derived cells, we used bone marrow transplantation to generate SR-BI-null; apoE-hypomorphic mice in which SR-BI expression was restored solely in bone marrow derived cells. SR-BI-null; apoE-hypomorphic mice were transplanted with SR-BI(+/+)apoE-hypomorphic, or control, autologous SR-BI-null; apoE-hypomorphic bone marrow. Four weeks later, mice were fed a high-fat, high-cholesterol, cholate-containing diet to induce coronary artery atherosclerosis. Mice transplanted with autologous bone marrow developed extensive aortic atherosclerosis and severe occlusive coronary artery atherosclerosis after 4 weeks of feeding. This was accompanied by myocardial fibrosis and increased heart weights. In contrast, restoration of SR-BI expression in bone marrow derived-cells reduced diet induced aortic and coronary artery atherosclerosis, myocardial fibrosis and the increase in heart weights in SR-BI-null; apoE-hypomorphic mice. Restoration of SR-BI in bone marrow derived cells did not, however, affect steady state lipoprotein cholesterol levels, but did reduce plasma levels of IL-6. Monocytes from SR-BI-null mice exhibited a greater capacity to bind to VCAM-1 and ICAM-1 than those from SR-BI(+/+) mice. Furthermore, restoration of SR-BI expression in bone marrow derived cells attenuated monocyte recruitment into atherosclerotic plaques in mice fed high fat, high cholesterol cholate containing diet. These data demonstrate directly that SR-BI in bone marrow-derived cells protects against both aortic and CA atherosclerosis. PMID:23967310

  13. Conditioned suppression, punishment, and aversion

    NASA Technical Reports Server (NTRS)

    Orme-Johnson, D. W.; Yarczower, M.

    1974-01-01

    The aversive action of visual stimuli was studied in two groups of pigeons which received response-contingent or noncontingent electric shocks in cages with translucent response keys. Presentation of grain for 3 sec, contingent on key pecking, was the visual stimulus associated with conditioned punishment or suppression. The responses of the pigeons in three different experiments are compared.

  14. Plasma suppression of beamstrahlung: Revision

    SciTech Connect

    Whittum, D.H.; Sessler, A.M.; Stewart, J.J.; Yu, S.S.

    1988-06-01

    We investigate the use of a plasma at the interaction point of two colliding beams to suppress beamstrahlung and related phenomena. We derive conditions for good current cancellation via plasma return currents and report on numerical simulations conducted to confirm our analytic results. 17 refs., 5 figs., 5 tabs.

  15. -uncertainty Anonymization by Partial Suppression

    E-print Network

    Zhu, Kenny Q.

    Results (a) Original Dataset TID Transaction 1 bread, milk, condom 2 bread, milk 3 milk, condom 4 flour, fruits 5 flour, condom 6 bread, fruits 7 fruits, condom (b) Global Suppression TID Transaction 1 bread, milk, condom 2 bread, milk 3 milk, condom 4 flour, fruits 5 flour, condom 6 bread, fruits 7 fruits

  16. DENDRITIC POLYMERS AS FIRE SUPPRESSANTS

    EPA Science Inventory

    This report describes an evaluation of the applicability of one of the latest advances in polymer technology (dendritic polymers) to suppressing fires, one of the greatest survivability threats to military personnel and vehicles. Certain types of alkali and transition metal compl...

  17. Fermionic suppression of dipolar relaxation.

    PubMed

    Burdick, Nathaniel Q; Baumann, Kristian; Tang, Yijun; Lu, Mingwu; Lev, Benjamin L

    2015-01-16

    We observe the suppression of inelastic dipolar scattering in ultracold Fermi gases of the highly magnetic atom dysprosium: the more energy that is released, the less frequently these exothermic reactions take place, and only quantum spin statistics can explain this counterintuitive effect. Inelastic dipolar scattering in nonzero magnetic fields leads to heating or to loss of the trapped population, both detrimental to experiments intended to study quantum many-body physics with strongly dipolar gases. Fermi statistics, however, is predicted to lead to a kinematic suppression of these harmful reactions. Indeed, we observe a 120-fold suppression of dipolar relaxation in fermionic versus bosonic Dy, as expected from theory describing universal inelastic dipolar scattering, though never before experimentally confirmed. Similarly, low inelastic cross sections are observed in spin mixtures, also with striking correspondence to predictions. The suppression of relaxation opens the possibility of employing fermionic dipolar species in studies of quantum many-body physics involving, e.g., synthetic gauge fields and pairing. PMID:25635544

  18. Individuals with metabolic diseases are at a higher risk of developing atherosclerosis, a leading cause of death in the United States and worldwide. Earlier studies have linked dyslipidemia to the initiation and

    E-print Network

    Azad, Abdul-Majeed

    Individuals with metabolic diseases are at a higher risk of developing atherosclerosis, a leading to the initiation and progression of atherosclerosis. However, recent clinical studies raised concerns about the efficacy of lowering plasma cholesterol levels in the progression of atherosclerosis. Although insulin

  19. Cell-derived microparticles in atherosclerosis: biomarkers and targets for pharmacological modulation?

    PubMed Central

    Baron, Morgane; Boulanger, Chantal M; Staels, Bart; Tailleux, Anne; Simionescu, M

    2012-01-01

    Abstract Cardiovascular diseases remain an important cause of morbi-mortality. Atherosclerosis, which predisposes to cardiovascular disorders such as myocardial infarction and stroke, develops silently over several decades. Identification of circulating biomarkers to evaluate cardiovascular event risk and pathology prognosis is of particular importance. Microparticles (MPs) are small vesicles released from cells upon apoptosis or activation. Microparticles are present in blood of healthy individuals. Studies showing a modification of their concentrations in patients with cardiovascular risk factors and after cardiovascular events identify MPs as potential biomarkers of disease. Moreover, the pathophysiological properties of MPs may contribute to atherosclerosis development. In addition, pharmacological compounds, used in the treatment of cardiovascular disease, can reduce plasma MP concentrations. Nevertheless, numerous issues remain to be solved before MP measurement can be applied as routine biological tests to improve cardiovascular risk prediction. In particular, prospective studies to identify the predictive values of MPs in pathologies such as cardiovascular diseases are needed to demonstrate whether MPs are useful biomarkers for the early detection of the disease and its progression. PMID:22050954

  20. Myeloperoxidase Levels Predict Accelerated Progression of Coronary Atherosclerosis in Diabetic Patients: Insights from Intravascular Ultrasound

    PubMed Central

    Kataoka, Yu; Shao, Mingyuan; Wolski, Kathy; Uno, Kiyoko; Puri, Rishi; Tuzcu, E. Murat; Hazen, Stanley L.; Nissen, Steven E.; Nicholls, Stephen J.

    2014-01-01

    Objective While inflammation has been proposed to contribute to the adverse cardiovascular outcome in diabetic patients, the specific pathways involved have not been elucidated. The leukocyte derived product, myeloperoxidase (MPO), has been implicated in all stages of atherosclerosis. The relationship between MPO and accelerated disease progression observed in diabetic patients has not been studied. Methods We investigated the relationship between MPO and disease progression in diabetic patients. 881 patients with angiographic coronary artery disease underwent serial evaluation of atherosclerotic burden with intravascular ultrasound. Disease progression in diabetic (n=199) and non-diabetic (n=682) patients, stratified by baseline MPO levels was investigated. Results MPO levels were similar in patients with and without diabetes (1362 vs. 1255 pmol/L, p=0.43). No relationship was observed between increasing quartiles of MPO and either baseline (p=0.81) or serial changes (p=0.43) in levels of percent atheroma volume (PAV) in non-diabetic patients. In contrast, increasing MPO quartiles were associated with accelerated PAV progression in diabetic patients (p=0.03). While optimal control of lipid and the use of high-dose statin were associated with less disease progression, a greater benefit was observed in diabetic patients with lower compared with higher MPO levels at baseline. Conclusions Increasing MPO levels are associated with greater progression of atherosclerosis in diabetic patients. This finding indicates the potential importance of MPO pathways in diabetic cardiovascular disease. PMID:24468151

  1. The glycosylation-dependent interaction of perlecan core protein with LDL: implications for atherosclerosis[S

    PubMed Central

    Xu, Yu-Xin; Ashline, David; Liu, Li; Tassa, Carlos; Shaw, Stanley Y.; Ravid, Katya; Layne, Matthew D.; Reinhold, Vernon; Robbins, Phillips W.

    2015-01-01

    Perlecan is a major heparan sulfate (HS) proteoglycan in the arterial wall. Previous studies have linked it to atherosclerosis. Perlecan contains a core protein and three HS side chains. Its core protein has five domains (DI–DV) with disparate structures and DII is highly homologous to the ligand-binding portion of LDL receptor (LDLR). The functional significance of this domain has been unknown. Here, we show that perlecan DII interacts with LDL. Importantly, the interaction largely relies on O-linked glycans that are only present in the secreted DII. Among the five repeat units of DII, most of the glycosylation sites are from the second unit, which is highly divergent and rich in serine and threonine, but has no cysteine residues. Interestingly, most of the glycans are capped by the negatively charged sialic acids, which are critical for LDL binding. We further demonstrate an additive effect of HS and DII on LDL binding. Unlike LDLR, which directs LDL uptake through endocytosis, this study uncovers a novel feature of the perlecan LDLR-like DII in receptor-mediated lipoprotein retention, which depends on its glycosylation. Thus, perlecan glycosylation may play a role in the early LDL retention during the development of atherosclerosis. PMID:25528754

  2. Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI

    PubMed Central

    Amirbekian, Vardan; Lipinski, Michael J.; Briley-Saebo, Karen C.; Amirbekian, Smbat; Aguinaldo, Juan Gilberto S.; Weinreb, David B.; Vucic, Esad; Frias, Juan C.; Hyafil, Fabien; Mani, Venkatesh; Fisher, Edward A.; Fayad, Zahi A.

    2007-01-01

    We investigated the ability of targeted immunomicelles to detect and assess macrophages in atherosclerotic plaque using MRI in vivo. There is a large clinical need for a noninvasive tool to assess atherosclerosis from a molecular and cellular standpoint. Macrophages play a central role in atherosclerosis and are associated with plaques vulnerable to rupture. Therefore, macrophage scavenger receptor (MSR) was chosen as a target for molecular MRI. MSR-targeted immunomicelles, micelles, and gadolinium–diethyltriaminepentaacetic acid (DTPA) were tested in ApoE?/? and WT mice by using in vivo MRI. Confocal laser-scanning microscopy colocalization, macrophage immunostaining and MRI correlation, competitive inhibition, and various other analyses were performed. In vivo MRI revealed that at 24 h postinjection, immunomicelles provided a 79% increase in signal intensity of atherosclerotic aortas in ApoE?/? mice compared with only 34% using untargeted micelles and no enhancement using gadolinium–DTPA. Confocal laser-scanning microscopy revealed colocalization between fluorescent immunomicelles and macrophages in plaques. There was a strong correlation between macrophage content in atherosclerotic plaques and the matched in vivo MRI results as measured by the percent normalized enhancement ratio. Monoclonal antibodies to MSR were able to significantly hinder immunomicelles from providing contrast enhancement of atherosclerotic vessels in vivo. Immunomicelles provided excellent validated in vivo enhancement of atherosclerotic plaques. The enhancement seen is related to the macrophage content of the atherosclerotic vessel areas imaged. Immunomicelles may aid in the detection of high macrophage content associated with plaques vulnerable to rupture. PMID:17215360

  3. High density lipoprotein-based contrast agents for multimodal imaging of atherosclerosis

    PubMed Central

    Skajaa, Torjus; Cormode, David P.; Falk, Erling; Mulder, Willem J. M.

    2010-01-01

    Lipoproteins, natural nanoparticles, have a well-recognized biological role and are highly suitable as a platform for delivering imaging agents. The ease with which both the exterior and interior of the particles can be modified permits the creation of multifunctional nanoparticles for imaging as well as the delivery of therapeutics. Importantly, their endogenous nature may make them biocompatible, biodegradable and allows them to avoid the recognition of the reticuloendothelial system. In particular, high density lipoproteins (HDL) are of interest, because of their small size they can easily cross the endothelium and penetrate the underlying tissue. We summarize here the progress in establishing HDL as a vector for delivering a variety of diagnostically active materials to vulnerable atherosclerotic plaques in mouse models of atherosclerosis. By loading various types of image-enhancing compounds into either the core or surface of HDL, they can be visualized by different imaging modalities (MRI, CT, optical). By re-routing of HDL away from plaque macrophages, imaging of biological processes in diseases besides atherosclerosis may also be achieved. PMID:19815819

  4. Imaging of Oxidation-Specific Epitopes in Atherosclerosis and Macrophage-Rich Vulnerable Plaques

    PubMed Central

    Briley-Saebo, Karen C.; Cho, Young Seok

    2010-01-01

    Oxidative stress, and in particular oxidation of lipoproteins, is a hallmark of atherosclerosis. Upon entry of lipoproteins into the vessel wall, a cascade of pro-atherogenic pathways is initiated whereby the reaction of reactive oxygen species with substrates amenable to oxidation, such as polyunsaturated fatty acids, generates a variety of oxidation-specific epitopes on lipoproteins, proteins in the vessel wall, and apoptotic macrophages. Several of these oxidation-specific epitopes have been well characterized and specific murine and fully human antibodies have been generated in our laboratory to detect them in the vessel wall. We have developed radionuclide, gadolinium and iron oxide based MRI techniques to noninvasively image oxidation-specific epitopes in atherosclerotic lesions. These approaches quantitate plaque burden and also allow detection of atherosclerosis regression and plaque stabilization. In particular, gadolinium micelles or lipid-coated ultrasmall superparamagnetic iron oxide particles containing oxidation-specific antibodies accumulate within macrophages in the artery wall, suggesting they may image the most unstable plaques. Translation of these approaches to humans may allow a sensitive technique to image and monitor high-risk atherosclerotic lesions and may guide optimal therapeutic interventions. PMID:21297859

  5. Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis

    PubMed Central

    Weih, Falk; Gräbner, Rolf; Hu, Desheng; Beer, Michael; Habenicht, Andreas J. R.

    2012-01-01

    Tertiary lymphoid organs (TLOs) emerge in tissues in response to non-resolving inflammation such as chronic infection, graft rejection, and autoimmune disease. We identified artery TLOs (ATLOs) in the adventitia adjacent to atherosclerotic plaques of aged hyperlipidemic ApoE?/? mice. ATLOs are structured into T cell areas harboring conventional dendritic cells and monocyte-derived DCs; B cell follicles containing follicular dendritic cells within activated germinal centers; and peripheral niches of plasma cells. ATLOs also show extensive neoangiogenesis, aberrant lymphangiogenesis, and high endothelial venule (HEV) neogenesis. Newly formed conduit networks connect the external lamina of the artery with HEVs in T cell areas. ATLOs recruit and generate lymphocyte subsets with opposing activities including activated CD4+ and CD8+ effector T cells, natural and induced CD4+ T regulatory (nTregs; iTregs) cells as well as B-1 and B-2 cells at different stages of differentiation. These data indicate that ATLOs organize dichotomic innate and adaptive immune responses in atherosclerosis. In this review we discuss the novel concept that dichotomic immune responses toward atherosclerosis-specific antigens are carried out by ATLOs in the adventitia of the arterial wall and that malfunction of the tolerogenic arm of ATLO immunity triggers transition from silent autoimmune reactivity to clinically overt disease. PMID:22783198

  6. Neoatherosclerosis: Coronary stents seal atherosclerotic lesions but result in making a new problem of atherosclerosis

    PubMed Central

    Komiyama, Hidenori; Takano, Masamichi; Hata, Noritake; Seino, Yoshihiko; Shimizu, Wataru; Mizuno, Kyoichi

    2015-01-01

    Chronic inflammation of the native vessel wall with infiltration of lipid-laden foamy macrophages through impaired endothelium results in atherosclerosis. Percutaneous coronary intervention, including metallic stent implantation, is now widely utilized for the treatment of atherosclerotic lesions of the coronary artery. Bare-metal stents and the subsequently developed drug-eluting stents seal the atherosclerosis and resolve lumen stenosis or obstruction of the epicardial coronary artery and myocardial ischemia. After stent implantation, neointima proliferates within the stented segment. Chronic inflammation caused by a foreign body reaction to the implanted stent and subsequent neovascularization, which is characterized by the continuous recruitment of macrophages into the vessel, result in the transformation of the usual neointima into an atheromatous neointima. Neointima with an atherosclerotic appearance, such as that caused by thin-cap fibroatheromas, is now recognized as neoatherosclerosis, which can sometimes cause in-stent restenosis and acute thrombotic occlusion originating from the stent segment following disruption of the atheroma. Neoatherosclerosis is emerging as a new coronary stent-associated problem that has not yet been resolved. In this review article, we will discuss possible mechanisms, clinical challenges, and the future outlook of neoatherosclerosis. PMID:26635925

  7. Combined endothelin receptor blockade evokes enhanced vasodilatation in patients with atherosclerosis.

    PubMed

    Böhm, Felix; Ahlborg, Gunvor; Johansson, Bo-Lennart; Hansson, Lars-Olof; Pernow, John

    2002-04-01

    Endothelin (ET)-1 causes vasoconstriction via ET(A) and ET(B) receptors located on vascular smooth muscle cells and vasodilatation via ET(B) receptors on endothelial cells. Studies in vitro indicate an upregulation of ET(B) receptors in atherosclerosis. The present study investigated the vascular effects evoked by endogenous ET-1 in atherosclerotic patients. Forearm blood flow (FBF) was measured with venous occlusion plethysmography in 10 patients with atherosclerosis and in 10 healthy control subjects during intra-arterial infusion of selective ET receptor antagonists. The ET(B) receptor antagonist BQ788 evoked a significant increase in FBF (31+/-13%) in the patients, whereas a 20+/-9% reduction was observed in the control subjects. The ET(A) receptor antagonist BQ123 combined with BQ788 evoked a marked increase in FBF (102+/-25%) in the patients compared with no effect in the control subjects (-3+/-9%, P<0.001 versus patients). The ET(A) receptor antagonist BQ123 increased FBF to a similar degree in patients (39+/-11%) as in control subjects (41+/-11%). The increase in FBF evoked by selective ET(A) receptor blockade was significantly (P<0.05) less than that evoked by combined ET(A)/ET(B) receptor blockade in the atherosclerotic patients. These observations suggest an enhanced ET-1-mediated vascular tone in atherosclerotic patients, which is at least partly due to increased ET(B)-mediated vasoconstriction. PMID:11950709

  8. Requirement of Apelin-Apelin Receptor System for Oxidative Stress-Linked Atherosclerosis

    PubMed Central

    Hashimoto, Tatsuo; Kihara, Minoru; Imai, Nozomi; Yoshida, Shin-ichiro; Shimoyamada, Hiroaki; Yasuzaki, Hiroaki; Ishida, Junji; Toya, Yoshiyuki; Kiuchi, Yoshihiro; Hirawa, Nobuhito; Tamura, Kouichi; Yazawa, Takuya; Kitamura, Hitoshi; Fukamizu, Akiyoshi; Umemura, Satoshi

    2007-01-01

    The recently identified endogenous peptide apelin and its specific apelin receptor (APJ) are currently being considered as potential regulators in vascular tissue. Previously, we reported apelin mediates phosphorylation of myosin light chain and elicits vasoconstriction in vascular smooth muscle. In this study, physiological roles of the apelin-APJ system were investigated on atherosclerosis. In APJ and apolipoprotein E double-knockout (APJ?/?ApoE?/?) mice fed a high-cholesterol diet, atherosclerotic lesions were dramatically reduced when compared with APJ+/+ ApoE?/? mice, in the absence of an effect of cholesterol levels. Immunohistochemical detection of smooth muscle cells, using a smooth muscle ?-actin antibody, showed greatly reduced staining for these cells in lesions of APJ?/?ApoE?/? mice fed a high-cholesterol diet. Vascular production of superoxide radicals and the expression of nicotinamide-adenine dinucleotide phosphate oxidase subunits were decreased in APJ?/?ApoE?/? mice compared with APJ+/+ApoE?/? mice fed a standard normal diet. In vascular smooth muscle cells, apelin induced nicotinamide-adenine dinucleotide phosphate oxidase subunit expression. Apelin also induced vascular smooth muscle cell proliferation, which was inhibited by superoxide dismutase or diphenylene iodonium. The apelin-APJ system is a mediator of oxidative stress in vascular tissue, and thus we propose it to be a critical factor in atherogenesis under high-cholesterol dietary conditions. APJ deficiency is preventative against oxidative stress-linked atherosclerosis. PMID:17884970

  9. Disturbed flow-activated p90RSK kinase accelerates atherosclerosis by inhibiting SENP2 function.

    PubMed

    Heo, Kyung-Sun; Le, Nhat-Tu; Cushman, Hannah J; Giancursio, Carolyn J; Chang, Eugene; Woo, Chang-Hoon; Sullivan, Mark A; Taunton, Jack; Yeh, Edward T H; Fujiwara, Keigi; Abe, Jun-ichi

    2015-03-01

    Disturbed blood flow (d-flow) causes endothelial cell (EC) dysfunction, leading to atherosclerotic plaque formation. We have previously shown that d-flow increases SUMOylation of p53 and ERK5 through downregulation of sentrin/SUMO-specific protease 2 (SENP2) function; however, it is not known how SENP2 itself is regulated by d-flow. Here, we determined that d-flow activated the serine/threonine kinase p90RSK, which subsequently phosphorylated threonine 368 (T368) of SENP2. T368 phosphorylation promoted nuclear export of SENP2, leading to downregulation of eNOS expression and upregulation of proinflammatory adhesion molecule expression and apoptosis. In an LDLR-deficient murine model of atherosclerosis, EC-specific overexpression of p90RSK increased EC dysfunction and lipid accumulation in the aorta compared with control animals; however, these pathologic changes were not observed in atherosclerotic mice overexpressing dominant negative p90RSK (DN-p90RSK). Moreover, depletion of SENP2 in these mice abolished the protective effect of DN-p90RSK overexpression. We propose that p90RSK-mediated SENP2-T368 phosphorylation is a master switch in d-flow-induced signaling, leading to EC dysfunction and atherosclerosis. PMID:25689261

  10. Liver-specific transgenic expression of cholesteryl ester hydrolase reduces atherosclerosis in Ldlr?/? mice[S

    PubMed Central

    Bie, Jinghua; Wang, Jing; Yuan, Quan; Kakiyama, Genta; Ghosh, Siddhartha S.; Ghosh, Shobha

    2014-01-01

    The liver plays a central role in the final elimination of cholesterol from the body either as bile acids or as free cholesterol (FC), and lipoprotein-derived cholesterol is the major source of total biliary cholesterol. HDL is the major lipoprotein responsible for removal and transport of cholesterol, mainly as cholesteryl esters (CEs), from the peripheral tissues to the liver. While HDL-FC is rapidly secreted into bile, the fate of HDL-CE remains unclear. We have earlier demonstrated the role of human CE hydrolase (CEH, CES1) in hepatic hydrolysis of HDL-CE and increasing bile acid synthesis, a process dependent on scavenger receptor BI expression. In the present study, we examined the hypothesis that by enhancing the elimination of HDL-CE into bile/feces, liver-specific transgenic expression of CEH will be anti-atherogenic. Increased CEH expression in the liver significantly increased the flux of HDL-CE to bile acids. In the LDLR?/? background, this enhanced elimination of cholesterol led to attenuation of diet-induced atherosclerosis with a consistent increase in fecal sterol secretion primarily as bile acids. Taken together with the observed reduction in atherosclerosis by increasing macrophage CEH-mediated cholesterol efflux, these studies establish CEH as an important regulator in enhancing cholesterol elimination and also as an anti-atherogenic target. PMID:24563511

  11. Fructose Metabolism and Relation to Atherosclerosis, Type 2 Diabetes, and Obesity

    PubMed Central

    Kolderup, Astrid; Svihus, Birger

    2015-01-01

    A high intake of sugars has been linked to diet-induced health problems. The fructose content in sugars consumed may also affect health, although the extent to which fructose has a particularly significant negative impact on health remains controversial. The aim of this narrative review is to describe the body's fructose management and to discuss the role of fructose as a risk factor for atherosclerosis, type 2 diabetes, and obesity. Despite some positive effects of fructose, such as high relative sweetness, high thermogenic effect, and low glycaemic index, a high intake of fructose, particularly when combined with glucose, can, to a larger extent than a similar glucose intake, lead to metabolic changes in the liver. Increased de novo lipogenesis (DNL), and thus altered blood lipid profile, seems to be the most prominent change. More studies with realistic consumption levels of fructose are needed, but current literature does not indicate that a normal consumption of fructose (approximately 50–60?g/day) increases the risk of atherosclerosis, type 2 diabetes, or obesity more than consumption of other sugars. However, a high intake of fructose, particularly if combined with a high energy intake in the form of glucose/starch, may have negative health effects via DNL. PMID:26199742

  12. Effects of Intravenous Injection of Porphyromonas gingivalis on Rabbit Inflammatory Immune Response and Atherosclerosis

    PubMed Central

    Lin, Gengbing; Chen, Shuai; Lei, Lang; You, Xiaoqing; Huang, Min; Luo, Lan; Li, Yanfen; Zhao, Xin; Yan, Fuhua

    2015-01-01

    The effects of intravenous injection of Porphyromonas gingivalis (Pg) on rabbit inflammatory immune response and atherosclerosis were evaluated by establishing a microamount Pg bacteremia model combined with high-fat diet. Twenty-four New Zealand rabbits were randomly divided into Groups A-D (n = 6). After 14 weeks, levels of inflammatory factors (C-reactive protein (CRP), tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1)) in peripheral blood were detected by ELISA. The aorta was subjected to HE staining. Local aortic expressions of toll-like receptor-2 (TLR-2), TLR-4, TNF-?, CRP, IL-6, matrix metallopeptidase-9, and MCP-1 were detected by real-time PCR, and those of nuclear factor-?B (NF-?B) p65, phospho-p38 mitogen-activated protein kinase (MAPK), and phospho-c-Jun N-terminal kinase (JNK) proteins were detected by Western blot. Intravenous injection of Pg to the bloodstream alone induced atherosclerotic changes and significantly increased systemic and local aortic expressions of inflammatory factors, NF-?B p65, phospho-p38-MAPK, and JNK, especially in Group D. Injection of microamount Pg induced inflammatory immune response and accelerated atherosclerosis, in which the NF-?B p65, p38-MAPK, and JNK signaling pathways played important roles. Intravenous injection of Pg is not the same as Pg from human periodontitis entering the blood stream. Therefore, our results cannot be extrapolated to human periodontitis. PMID:26063970

  13. Combining OCT and a fluorescence intensity imaging method for atherosclerosis detection

    NASA Astrophysics Data System (ADS)

    Liang, Shanshan; Saidi, Arya; Jing, Joe; Liu, Gangjun; Yin, Jiechen; Narula, Jagat; Chen, Zhongping

    2012-02-01

    Coronary heart disease (like myocardial infarction) is caused by atherosclerosis. It cause over 30% of all deaths in North America and are the most common cause of death in European men under 65 years of age and the second most common cause in women. To diagnose this atherosclerosis before it gets rupture is the most effect way to increase the chance of survival for patients who suffer from this disease. The crucial tusk is how to find out vulnerable plaques. In resent years optical coherence tomography (OCT) has become a very useful tool for intravascular imaging, since it has high axial and transverse resolution. OCT can tell the detail structure inside the plaque like the thickness of plaque cap which is an important factor to identify vulnerable plaques. But we still need to find out the biochemical characteristics that is unique for vulnerable plaques (like inflammation). Fluorescence molecular imaging is a standard way to exam the biochemical property of biological samples. So we integrate these two techniques together into one probe. Our probe is comprised of a double-clad fiber (DCF) and a grin lens, and rotates with a micro mirror in front. The single-mode inner core of the DCF transmits both OCT and fluorescence excitation light, and the multimode inner cladding is used to detect fluorescence signal. In vitro result shows that this is a possible way for more accurate diagnose of vulnerable plaques.

  14. The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

    PubMed Central

    She, Zhi-Gang; Chen, Hou-Zao; Yan, Yunfei; Li, Hongliang

    2012-01-01

    Abstract The paraoxonase (PON) gene cluster contains three adjacent gene members, PON1, PON2, and PON3. Originating from the same fungus lactonase precursor, all of the three PON genes share high sequence identity and a similar ? propeller protein structure. PON1 and PON3 are primarily expressed in the liver and secreted into the serum upon expression, whereas PON2 is ubiquitously expressed and remains inside the cell. Each PON member has high catalytic activity toward corresponding artificial organophosphate, and all exhibit activities to lactones. Therefore, all three members of the family are regarded as lactonases. Under physiological conditions, they act to degrade metabolites of polyunsaturated fatty acids and homocysteine (Hcy) thiolactone, among other compounds. By detoxifying both oxidized low-density lipoprotein and Hcy thiolactone, PONs protect against atherosclerosis and coronary artery diseases, as has been illustrated by many types of in vitro and in vivo experimental evidence. Clinical observations focusing on gene polymorphisms also indicate that PON1, PON2, and PON3 are protective against coronary artery disease. Many other conditions, such as diabetes, metabolic syndrome, and aging, have been shown to relate to PONs. The abundance and/or activity of PONs can be regulated by lipoproteins and their metabolites, biological macromolecules, pharmacological treatments, dietary factors, and lifestyle. In conclusion, both previous results and ongoing studies provide evidence, making the PON cluster a prospective target for the treatment of atherosclerosis. Antioxid. Redox Signal. 16, 597–632. PMID:21867409

  15. Liver-specific transgenic expression of cholesteryl ester hydrolase reduces atherosclerosis in Ldlr-/- mice.

    PubMed

    Bie, Jinghua; Wang, Jing; Yuan, Quan; Kakiyama, Genta; Ghosh, Siddhartha S; Ghosh, Shobha

    2014-04-01

    The liver plays a central role in the final elimination of cholesterol from the body either as bile acids or as free cholesterol (FC), and lipoprotein-derived cholesterol is the major source of total biliary cholesterol. HDL is the major lipoprotein responsible for removal and transport of cholesterol, mainly as cholesteryl esters (CEs), from the peripheral tissues to the liver. While HDL-FC is rapidly secreted into bile, the fate of HDL-CE remains unclear. We have earlier demonstrated the role of human CE hydrolase (CEH, CES1) in hepatic hydrolysis of HDL-CE and increasing bile acid synthesis, a process dependent on scavenger receptor BI expression. In the present study, we examined the hypothesis that by enhancing the elimination of HDL-CE into bile/feces, liver-specific transgenic expression of CEH will be anti-atherogenic. Increased CEH expression in the liver significantly increased the flux of HDL-CE to bile acids. In the LDLR(-/-) background, this enhanced elimination of cholesterol led to attenuation of diet-induced atherosclerosis with a consistent increase in fecal sterol secretion primarily as bile acids. Taken together with the observed reduction in atherosclerosis by increasing macrophage CEH-mediated cholesterol efflux, these studies establish CEH as an important regulator in enhancing cholesterol elimination and also as an anti-atherogenic target. PMID:24563511

  16. Endothelial Expression of Scavenger Receptor Class B, Type I Protects against Development of Atherosclerosis in Mice

    PubMed Central

    Vaisman, Boris L.; Vishnyakova, Tatyana G.; Freeman, Lita A.; Amar, Marcelo J.; Demosky, Stephen J.; Liu, Chengyu; Stonik, John A.; Sampson, Maureen L.; Pryor, Milton; Bocharov, Alexander V.; Eggerman, Thomas L.; Patterson, Amy P.; Remaley, Alan T.

    2015-01-01

    The role of scavenger receptor class B, type I (SR-BI) in endothelial cells (EC) was examined in several novel transgenic mouse models expressing SR-BI in endothelium of mice with normal C57Bl6/N, apoE-KO, or Scarb1-KO backgrounds. Mice were also created expressing SR-BI exclusively in endothelium and liver. Endothelial expression of the Tie2-Scarb1 transgene had no significant effect on plasma lipoprotein levels in mice on a normal chow diet but on an atherogenic diet, significantly decreased plasma cholesterol levels, increased plasma HDL cholesterol (HDL-C) levels, and protected mice against atherosclerosis. In 8-month-old apoE-KO mice fed a normal chow diet, the Tie2-Scarb1 transgene decreased aortic lesions by 24%. Mice expressing SR-BI only in EC and liver had a 1.5 ± 0.1-fold increase in plasma cholesterol compared to mice synthesizing SR-BI only in liver. This elevation was due mostly to increased HDL-C. In EC culture studies, SR-BI was found to be present in both basolateral and apical membranes but greater cellular uptake of cholesterol from HDL was found in the basolateral compartment. In summary, enhanced expression of SR-BI in EC resulted in a less atherogenic lipoprotein profile and decreased atherosclerosis, suggesting a possible role for endothelial SR-BI in the flux of cholesterol across EC. PMID:26504816

  17. Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis

    PubMed Central

    Kojima, Yoko; Downing, Kelly; Kundu, Ramendra; Miller, Clint; Dewey, Frederick; Lancero, Hope; Raaz, Uwe; Perisic, Ljubica; Hedin, Ulf; Schadt, Eric; Maegdefessel, Lars; Quertermous, Tom; Leeper, Nicholas J.

    2014-01-01

    Genetic variation at the chromosome 9p21 risk locus promotes cardiovascular disease; however, it is unclear how or which proteins encoded at this locus contribute to disease. We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), in mice promotes vascular SMC apoptosis and aneurysm progression. Here, we investigated the role of Cdnk2b in atherogenesis and found that in a mouse model of atherosclerosis, deletion of Cdnk2b promoted advanced development of atherosclerotic plaques composed of large necrotic cores. Furthermore, human carriers of the 9p21 risk allele had reduced expression of CDKN2B in atherosclerotic plaques, which was associated with impaired expression of calreticulin, a ligand required for activation of engulfment receptors on phagocytic cells. As a result of decreased calreticulin, CDKN2B-deficient apoptotic bodies were resistant to efferocytosis and not efficiently cleared by neighboring macrophages. These uncleared SMCs elicited a series of proatherogenic juxtacrine responses associated with increased foam cell formation and inflammatory cytokine elaboration. The addition of exogenous calreticulin reversed defects associated with loss of Cdkn2b and normalized engulfment of Cdkn2b-deficient cells. Together, these data suggest that loss of CDKN2B promotes atherosclerosis by increasing the size and complexity of the lipid-laden necrotic core through impaired efferocytosis. PMID:24531546

  18. A novel method for quantifying spatial correlations between patterns of atherosclerosis and hemodynamic factors.

    PubMed

    Peiffer, Véronique; Bharath, Anil A; Sherwin, Spencer J; Weinberg, Peter D

    2013-02-01

    Studies investigating the relation between the focal nature of atherosclerosis and hemodynamic factors are employing increasingly rigorous approaches to map the disease and calculate hemodynamic metrics. However, no standardized methodology exists to quantitatively compare these distributions. We developed a statistical technique that can be used to determine if hemodynamic and lesion maps are significantly correlated. The technique, which is based on a surrogate data analysis, does not require any assumptions (such as linearity) on the nature of the correlation. Randomized sampling was used to ensure the independence of data points, another basic assumption of commonly-used statistical methods that is often disregarded. The novel technique was used to compare previously-obtained maps of lesion prevalence in aortas of immature and mature cholesterol-fed rabbits to corresponding maps of wall shear stress, averaged across several animals in each age group. A significant spatial correlation was found in the proximal descending thoracic aorta, but not further downstream. Around intercostal branch openings the correlation was borderline significant in immature but not in mature animals. The results confirm the need for further investigation of the relation between the localization of atherosclerosis and blood flow, in conjunction with appropriate statistical techniques such as the method proposed here. PMID:23445068

  19. ADAM15 contributes to atherosclerosis by mediating endothelial barrier dysfunction via Src family kinase activity

    PubMed Central

    Sun, Chongxiu; Wu, Mack H.; Lee, Eugene S.; Yuan, Sarah Y.

    2012-01-01

    Objective Endothelium dysfunction is an initiating factor in atherosclerosis. ADAM15 is a multi-domain metalloprotease recently identified as a regulator of endothelial permeability. However, whether and how ADAM15 contributes to atherosclerosis remains unknown. Methods and Results Genetic ablation of ADAM15 in apolipoprotein E-deficient mice lead to a significant reduction in aortic atherosclerotic lesion size (by 52%), plaque macrophage infiltration (by 69%), and smooth muscle cell deposition (by 82%). In vitro studies implicated endothelial derived ADAM15 in barrier dysfunction and monocyte transmigration across mouse aortic and human umbilical vein endothelial cell monolayers. This role of ADAM15 depended on intact functioning of the cytoplasmic domain, as evidenced in experiments with site-directed mutagenesis targeting the metalloprotease active site (E349A), the disintegrin domain (RDG?TDD) or the cytoplasmic tail. Further investigations revealed that ADAM15-induced barrier dysfunction was concomitant with dissociation of endothelial adherens junctions (VE-cadherin/?-catenin), an effect that was sensitive to Src family kinase (SFK) inhibition. Through siRNA-mediated knockdown of distinct SFK members, c-Src and c-Yes were identified as important mediators of these junctional effects of ADAM15. Conclusions These results suggest that endothelial cell-derived ADAM15, signaling through c-Src and c-Yes, contributes to atherosclerotic lesion development by disrupting adherence junction integrity and promoting monocyte transmigration. PMID:22904271

  20. Independent association between serum sclerostin levels and carotid artery atherosclerosis in prevalent haemodialysis patients

    PubMed Central

    Kirkpantur, Alper; Balci, Mustafa; Turkvatan, Aysel; Afsar, Baris

    2015-01-01

    Background Sclerostin is a soluble inhibitor of the Wnt signalling pathway and has been shown to be associated with decreased bone turnover and vascular and/or valvular calcification in patients with chronic kidney disease. Common carotid artery intima-media thickness (CIMT) assessment and common carotid artery (CCA) plaque identification with ultrasound imaging are well-recognized tools for the identification and monitoring of atherosclerosis. The aim of the present study was to investigate whether the circulating levels of sclerostin might be associated with carotid artery atherosclerosis in prevalent haemodialysis patients. Methods In this cross-sectional study, serum sclerostin concentrations were measured using a commercially available enzyme-linked immunosorbent assay kit. CIMT was measured and carotid plaques were identified by B-mode and Doppler ultrasound imaging. Results One hundred and twenty-two prevalent haemodialysis patients were involved in the study. Serum sclerostin levels were higher in patients with plaques in CCA than patients free of plaques (227 ± 166 versus 117 ± 91 pmol/L, P = 0.016). A significant correlation was recorded between serum sclerostin levels and CIMT (r = 0.459, P < 0.0001). In the multiple regression analysis, sclerostin concentrations were one of the independent factors that remained significantly associated with CIMT. Conclusion Sclerostin is independently associated with CIMT although further studies are needed. PMID:26613034

  1. Oxidized LDL and Fructosamine Associated with Severity of Coronary Artery Atherosclerosis in Insulin Resistant Pigs Fed a High Fat/High NaCl Diet

    PubMed Central

    Nichols, Timothy C.; Merricks, Elizabeth P.; Bellinger, Dwight A.; Raymer, Robin A.; Yu, Jing; Lam, Diana; Koch, Gary G.; Busby, Walker H.; Clemmons, David R.

    2015-01-01

    Background Insulin-resistant subjects develop more severe and diffuse coronary artery atherosclerosis than insulin-sensitive controls but the mechanisms that mediate this atherosclerosis phenotype are unknown. Research Objective To determine the metabolic parameters that associate with the severity of coronary atherosclerosis in insulin resistant pigs fed a high fat/high NaCl diet. Key Methods The primary endpoint was severity of coronary atherosclerosis in adult pigs (Sus scrofa, n = 37) fed a high fat diet that also contained high NaCl (56% above recommended levels) for 1 year. Principal Findings Twenty pigs developed severe and diffuse distal coronary artery atherosclerosis (i.e., severe = intimal area as a percent medial area > 200% in at least 2 coronary artery cross sections and diffuse distal = intimal area as a percent medial area ? 150% over 3 sections separated by 2 cm in the distal half of the coronary artery). The other 17 pigs had substantially less coronary artery atherosclerosis. All 37 pigs had blood pressure in a range that would be considered hypertensive in humans and developed elevations in total and LDL and HDL cholesterol, weight gain, increased backfat, and increased insulin resistance (Bergman Si) without overt diabetes. Insulin resistance was not associated with atherosclerosis severity. Five additional pigs fed regular pig chow also developed increased insulin resistance but essentially no change in the other variables and little to no detectible coronary atherosclerosis. Most importantly, the 20 high fat/high NaCl diet -fed pigs with severe and diffuse distal coronary artery atherosclerosis had substantially greater increases (p< 0.05) in oxidized LDL (oxLDL) and fructosamine consistent with increased protein glycation. Conclusion In pigs fed a high fat/high NaCl diet, glycated proteins are induced in the absence of overt diabetes and this degree of increase is associated with the development of severe and diffuse distal coronary artery atherosclerosis. PMID:26147990

  2. Noise suppressing capillary separation system

    DOEpatents

    Yeung, E.S.; Xue, Y.

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans. 13 figs.

  3. Atherosclerosis and atherosensitivity in two southwest Algerian desert rodents, Psammomys obesus and Gerbillus gerbillus, and in Rattus norvegicus

    PubMed Central

    El-Aoufi, Salima; Lazourgui, Mohamed-Amine; Griene, Lakhdar; Maouche, Boubekeur

    2012-01-01

    Cardiovascular disease, including atherosclerosis, is the leading cause of death in patients with diabetes worldwide; thus, it is a major medical concern. The endothelium contributes to the control of many vascular functions, and clinical observations show that it is a primary target for diabetic syndrome. To get better insight into the mechanisms underlying atherosclerosis, we studied the interspecific differences in the arterial metabolisms of two, Psammomys obesus and Gerbillus gerbillus, as well as Rattus norvegicus (Wistar rat), well known for its atheroresistance. Twenty-two enzymatic activities and six macromolecular substances were histochemically compared in the two desert species and in Wistar aortas (abdominal and thoracic) and arteries (femoral and caudal) embedded in a common block. In the healthy adult rodents, enzyme activities were very intense. They demonstrated that aortic myocytes are capable of various synthesis and catabolism processes. However, considering the frequency of atherosclerosis and its phenotypes, significant differences appeared between the species studied. Our comparative study shows that aortic atherosensitive animals have several common metabolic characteristics, which are found in Psammomys rich in metachromatic glycosaminoglycans (involved in the inhibition of lipolysis and in calcification of the organic matrix), reduced activity in enzymes related to the Krebs cycle (weakening energetic power), and low lipolytic enzyme, adenosine triphosphatase, and adenosine diphosphatase activities. However, the most fundamental pathophysiological difference is the low lipolytic power of the aorta of Psammomys when compared to Wistar rats. This characteristic determines its atherosensitivity and makes this animal model more applicable to the experimental development of atherosclerosis. PMID:23055758

  4. Overweight Is a Major Contributor to Atherosclerosis in Systemic Lupus Erythematosus Patients at Apparent Low Risk for Cardiovascular Disease

    PubMed Central

    Sacre, Karim; Escoubet, Brigitte; Zennaro, Maria-Christina; Chauveheid, Marie-Paule; Gayat, Etienne; Papo, Thomas

    2015-01-01

    Abstract Cardiovascular disease (CVD) is the main cause of death in systemic lupus erythematosus (SLE) patients. We aimed to determine whether overweight (defined as a body mass index [BMI] > 25?kg/m2) contributed to subclinical atherosclerosis in SLE patients at low risk for CVD according to traditional factors. Wall thickness of the internal carotid artery (ICWT) measured at the carotid bulb and carotid plaques were assessed in 49 SLE patients asymptomatic for CVD and 49 controls matched on Framingham score. Factors associated to ICWT were identified and multivariate analysis was performed. SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (mean 1.9?±?3.5 in SLE vs 1.8?±?3.2% in controls, P?=?0.37). ICWT (P?atherosclerosis (OR [95% confidence interval, CI]: 3.53 [1.36–9.14]; P?=?0.009). Older age, higher BMI, and higher Framingham score were associated with atherosclerosis in SLE patients in univariate analysis. In multivariate analysis, only the association with overweight remained significant (OR [95% CI]: 4.13 [1.02–16.75]; P?=?0.047). Overweight is a major contributor to atherosclerosis in SLE patients at apparent low risk for CVD. PMID:26632902

  5. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

    SciTech Connect

    Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

    2003-09-01

    Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

  6. Dysfunctional HDL containing L159R apoA-I leads to exacerbation of atherosclerosis in hyperlipidemic mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, the effect of the mutation L159R apoA-I or apoA-IL159R (FIN) was assessed. apoA-IL159R (FIN) is associated with a dominant negative phenotype, displaying hypoalphaproteinemia and an increased risk for atherosclerosis in humans. Transgenic mice lines were created through strategic mati...

  7. An Educational Device for a Hands-on Activity to Visualize the Effect of Atherosclerosis on Blood Flow

    ERIC Educational Resources Information Center

    de Almeida, J. P. P. G. L.; de Lima, J. L. M. P.

    2013-01-01

    An educational device was created to develop a hands-on activity to illustrate how atherosclerosis can dramatically reduce blood flow in human vessels. The device was conceived, designed, and built at the University of Coimbra, in response to a request from the Exploratorio Infante D. Henrique Science Centre Museum, where it is presently…

  8. Paraoxonase-3 is depleted from the high-density lipoproteins of autoimmune disease patients with subclinical atherosclerosis.

    PubMed

    Marsillach, Judit; Becker, Jessica O; Vaisar, Tomas; Hahn, Bevra H; Brunzell, John D; Furlong, Clement E; de Boer, Ian H; McMahon, Maureen A; Hoofnagle, Andrew N

    2015-05-01

    Patients with autoimmune diseases have a significantly increased risk of developing cardiovascular disease. In disease, high-density lipoprotein (HDL) particles lose their anti-inflammatory and antioxidant properties and become dysfunctional. The purpose of this study was to test the hypothesis that alterations in the HDL proteomic profile are associated with subclinical atherosclerosis and HDL dysfunction in patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and type 1 diabetes. Targeted proteomics was used to quantify the relative abundance of 18 proteins in HDL from SLE patients with and without atherosclerotic plaque detectable by carotid ultrasound. Changes in the proteomic profile were compared against the in vitro ability of HDL to protect against lipid oxidation. The same proteins were quantified in HDL from patients with type 1 diabetes with or without coronary artery calcification as determined by computed tomography. In each population, paraoxonase-3 (PON3), a potent antioxidant protein, was depleted from the HDL of patients with subclinical atherosclerosis. PON3 expression in HDL was positively correlated with HDL antioxidant function. These results suggest that PON3 may be an important protein in preventing atherosclerosis and highlight the importance of antioxidant proteins in the prevention of atherosclerosis in vivo. PMID:25723336

  9. Atherosclerosis in ancient humans, accelerated aging syndromes and normal aging: is lamin a protein a common link?

    PubMed

    Miyamoto, Michael I; Djabali, Karima; Gordon, Leslie B

    2014-06-01

    Imaging studies of ancient human mummies have demonstrated the presence of vascular calcification that is consistent with the presence of atherosclerosis. These findings have stimulated interest in the underlying biological processes that might impart to humans an inherent predisposition to the development of atherosclerosis. Clues to these processes may possibly be found in accelerated aging syndromes, such as Hutchinson-Gilford progeria syndrome (HGPS), an ultra-rare disorder characterized by premature aging phenotypes, including very aggressive forms of atherosclerosis, occurring in childhood. The genetic defect in HGPS eventuates in the production of a mutant form of the nuclear structural protein lamin A, called progerin, which is thought to interfere with normal nuclear functioning. Progerin appears to be expressed in vascular cells, resulting in vessel wall cell loss and replacement by fibrous tissue, reducing vessel compliance and promoting calcification, leading to the vascular dysfunction and atherosclerosis seen in HGPS. Interestingly, vascular progerin is detectable in lower levels, in an age-related manner, in the general population, providing the basis for further study of the potential role of abnormal forms of lamin A in the atherosclerotic process of normal aging. PMID:25667091

  10. Risk of Atherosclerosis and Helicobacter pylori Infection according to CD14 Promotor Polymorphism in Healthy Korean Population

    PubMed Central

    Kang, Sung-Goo; Chung, Woo Chul; Song, Sang-Wook; Lee, Hyewon; Kang, Donghoon; Lee, Kang-Moon

    2013-01-01

    Background and Aim. We aim to elucidate the association of risk factors for atherosclerosis and H. pylori infection according to the promotor polymorphism of the CD14 gene in healthy Korean population. Methods. The patients who visited our hospital for routine health examinations and 266 healthy adults (170 males and 96 females) were enrolled in this study. The promotor polymorphism at ?159C/T of the CD14 gene was determined by PCR-restriction fragment length polymorphism analysis. According to genetic polymorphism and H. pylori infection, we analyzed the risk of atherosclerosis. Results. The genotype frequencies were CC 7.9%, CT 45.1%, and TT 47.0%, respectively. There were no differences between specific genotypes of CD14 gene and H. pylori infection rate. As for HDL cholesterol level, there were significant differences among the three genotypes (P < 0.01). In subjects with H. pylori infection, no significant differences were observed between specific genotypes of CD14 gene and the risk factors of atherosclerosis. Conclusion. The promotor polymorphism at ?159C/T of the CD14 gene was associated with the risk factor of atherosclerosis in healthy Korean population. However, it was not associated with the rate of H. pylori infection and H. pylori induced atherosclerotic risk. PMID:24228026

  11. Association of Angiotensin-Converting Enzyme Genotype, Insertion/Deletion Polymorphism and Saphenous Vein Graft Atherosclerosis in Iranian Patients

    PubMed Central

    Zeinali, Neda; Hashemi, Mohammad; Mirmohammadsadeghi, Mohsen; Mirmohammadsadeghi, Hamid; Eskandari, Nahid; Sabzghabaee, Ali Mohammad

    2015-01-01

    OBJECTIVE The aim of this study was to evaluate possible interactions among Angiotensin-I converting enzyme genotype, insertion/deletion polymorphism and atherosclerosis of vein grafts in Iranian patients, and characterize their clinical and demographic profile. METHODS In this cross-sectional study, patients who underwent coronary artery bypass graft surgery more than five years ago, were included for angiographic analysis. Atherosclerosis was determined by quantitative angiography and adjusted Gensini score. The gene angiotensin converting enzyme I/D polymorphism was detected by polymerase chain reaction. RESULTS A total of 102 patients participated in this study. Eighty-four patients were male. The frequency distribution of DD, ID and II polymorphism were 23.6%, 62.7% and 13.7% respectively. There were no differences among genotypic groups in age, sex, number of risk factors, number of vein grafts and months since bypass surgery. According to adjusted Gensini score [0.18±0.12 (II) vs. 0.11±0.09 (ID) and 0.1±0.09 (DD) P=0.021] the II genotype was associated with severity of vein graft atherosclerosis. CONCLUSION Although there are conflicting results about gene angiotensin converting enzyme I/D polymorphism and the degree of venous bypass graft degeneration, this study suggests an association between ACE genotype II and atherosclerosis of saphenous vein grafts, however, large samples considering clinical, demographic and ethnic profile are necessary to confirm these results.

  12. Trans-unsaturated fatty acids and acrylamide in food as potential atherosclerosis progression factors. Based on own studies.

    PubMed

    Naruszewicz, Marek; Daniewski, Marek; Nowicka, Grazyna; Koz?owska-Wojciechowska, Ma?gorzata

    2003-01-01

    Atherosclerosis is a chronic pathological process and it is generelly accepted that lipids, coagulation and inflammatory factors play an important role in its development. Environmental factors such as bed diet and cigarette smoking strongly stimulate initation and progression of atherosclerotic changes in the artery wall. It has been recognized that deeply processed food may be a source of various factors potentiating processes related to atherosclerosis development among which inflammatory processes are of great importance. The aim of our studies was to find out if the trans-unsaturated fatty acids as well as acrylamide present in foods have the potential to provoke pro-inflammatory states in the body and enhance atherosclerosis risk. The results of our in vitro studies have shown that trans fatty acids cause a significant increase in secretion of reactive oxygen species, interleukin-6, tumor necrosis factor a and metalloproteinase-9, and enhance apoptosis. It indicates that in vivo trans-fatty acids may distroy the endothelium integrity and cause plaque rupture. Our in vivo studies in the group of healthy volunteers have shown that the consumption of potato chips rich in acrylamide cause the significant increase in plasma C-reactive protein and homocysteine concentrations. Enhanced CRP and HCY levels are accepted markers of enhanced atherosclerosis risk. PMID:15058816

  13. Proteomic Analysis of Aortae from Human Lipoprotein(a) Transgenic Mice Shows an Early Metabolic Response Independent of Atherosclerosis

    PubMed Central

    Rodger, Euan J.; Suetani, Rachel J.; Jones, Gregory T.; Kleffmann, Torsten; Carne, Alan; Legge, Michael; McCormick, Sally P. A.

    2012-01-01

    Background Elevated low density lipoprotein (LDL) and lipoprotein(a) are independent risk factors for the development of atherosclerosis. Using a proteomic approach we aimed to determine early changes in arterial protein expression in transgenic mice containing both human LDL and lipoprotein(a) in circulation. Methods and Results Plasma lipid analyses showed the lipoprotein(a) transgenic mice had significantly higher lipid levels than wildtype, including a much increased LDL and high density lipoprotein (HDL) cholesterol. Analysis of aortae from lipoprotein(a) mice showed lipoprotein(a) accumulation but no lipid accumulation or foam cells, leaving the arteries essentially atherosclerosis free. Using two-dimensional gel electrophoresis and mass spectrometry, we identified 34 arterial proteins with significantly altered abundance (P<0.05) in lipoprotein(a) transgenic mice compared to wildtype including 17 that showed a ?2 fold difference. Some proteins of interest showed a similarly altered abundance at the transcript level. These changes collectively indicated an initial metabolic response that included a down regulation in energy, redox and lipid metabolism proteins and changes in structural proteins at a stage when atherosclerosis had not yet developed. Conclusions Our study shows that human LDL and lipoprotein(a) promote changes in the expression of a unique set of arterial proteins which may be early indicators of the metabolic disturbances preceding atherosclerosis. PMID:22276189

  14. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Gene Is a Risk Factor of Large-Vessel Atherosclerosis Stroke

    PubMed Central

    Abboud, Shérine; Karhunen, Pekka J.; Lütjohann, Dieter; Goebeler, Sirkka; Luoto, Teemu; Friedrichs, Silvia; Lehtimaki, Terho; Pandolfo, Massimo; Laaksonen, Reijo

    2007-01-01

    Background/Purpose Genetic variation in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been recently identified as an important determinant of plasma LDL-cholesterol and severity of coronary heart disease. We studied whether the PCSK9 gene is linked to the risk of ischemic stroke (IS) and with the development of intracranial atherosclerosis. Methods/Results The pivotal E670G polymorphism, tagging an important haplotype of the PCSK9 gene, was genotyped in two independent studies. The Belgium Stroke Study included 237 middle aged (45–60) Belgian patients, with small-vessel occlusion (SVO) and large-vessel atherosclerosis stroke (LVA), and 326 gender and ethnicity matched controls (>60 yrs) without a history of stroke. In multivariate analysis the minor allele (G) carriers appeared as a significant predictor of LVA (OR?=?3.52, 95% CI 1.25–9.85; p?=?0.017). In a Finnish crossectional population based consecutive autopsy series of 604 males and females (mean age 62.5 years), G-allele carriers tended to have more severe allele copy number-dependent (p?=?0.095) atherosclerosis in the circle of Willis and in its branches. Conclusion Our findings in this unique combination of clinical and autopsy data, provide evidence that PCSK9 gene associates with the risk of LVA stroke subtype, and suggest that the risk is mediated by the severity of intracranial atherosclerosis. PMID:17940607

  15. Mathematical and physical modelling of atherosclerosis in terms of the alterations of the dynamic electrical impedance of the arteries

    NASA Astrophysics Data System (ADS)

    Giannoukos, Georgios

    2012-09-01

    In this paper a detailed mathematical and physical model is presented in order to calculate the bioimpedance of both a healthy artery and an artery affected by atherosclerosis. This model allows us to compare the reaction of a healthy artery with that of a defective one by changing the values of resistance.

  16. The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits

    PubMed Central

    2013-01-01

    Background Atherosclerosis has been widely accepted as an inflammatory disease of vascular, adhesion molecules play an important role in the early progression of it. The aim of the present study was to evaluate the effect of kaempferol on the inflammatory molecules such as E-selectin (E-sel), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesionmolecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) in high cholesterol induced atherosclerosis rabbit models. Methods Thirty male New Zealand white (NZW) rabbits were randomly divided into five groups, control group, model group, fenofibrate (12mg/kg) group and kaempferol groups (150 mg/kg and 30 mg/kg). The rabbits were fed with a normal diet or a high cholesterol diet for 10 weeks. Levels of blood lipids, serum tumour-necrosis factor-alpha (TNF-?) and serum interleukin-1beta (IL-1?) were detected at the end of the sixth and tenth week. Malonaldehyde (MDA) level and superoxide dismutase (SOD) activity in serum were also determined. Lesion areas of the aorta were measured with morphometry analysis after ten weeks. Gene expression of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas was determined by RT-PCR (reverse transcription-polymerase chain reaction). Immunohistochemical staining was employed to measure protein expression of E-sel, ICAM-1, VCAM-1 and MCP-1. Results Model rabbits fed with ten weeks of high-cholesterol diet developed significant progression of atherosclerosis. Compared with the control, levels of blood lipids, TNF-?, IL-1? and MDA increased markedly in serum of model rabbits, while SOD levels decreased. Gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in atherosclerotic aortas increased remarkably in model group. However, comparing to the model rabbits, levels of TNF-?, IL-1? and MDA decreased significantly and serum SOD activity increased, gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas decreased significantly with the treatment of kaempferol. Conclusion Kaempferol shows anti-atherosclerotic effect by modulating the gene and protein expression of inflammatory molecules. PMID:23895132

  17. A nuclear microscopy study of trace elements Ca, Fe, Zn and Cu in atherosclerosis

    NASA Astrophysics Data System (ADS)

    Watt, F.; Rajendran, R.; Ren, M. Q.; Tan, B. K. H.; Halliwell, B.

    2006-08-01

    Quantitative mapping of trace elements Ca, Fe, Zn and Cu can be achieved in biological tissue using a nuclear microprobe. Presented here is a brief review of the work we have carried out in the last decade using the nuclear microscope to try and elucidate the role of trace elements Fe, Zn, Cu and Ca in induced atherosclerosis in New Zealand White rabbits fed on a 1% cholesterol diet. The lesions were studied using nuclear microscopy, incorporating a combination of ion beam techniques: particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and scanning transmission ion microscopy (STIM). Iron is present in early lesions at concentrations around seven times higher than the artery wall. Measurements of localized lesion iron concentrations were observed to be highly correlated with the depth of the lesion in the artery wall for each individual animal, implying that local elevated concentrations may provide an accelerated process of atherosclerosis in specific regions of the artery. When the rabbits were kept mildly anaemic, thereby reducing iron levels in the lesion, the progression of the disease was significantly slowed. Iron chelation using desferal showed that early treatment (three weeks into the high fat diet) for relatively long periods (nine weeks) significantly retarded the progression of the disease. Zinc is depleted in the lesion and is also observed to be anti-correlated with local lesion development and feeding the rabbits on a high fat diet with zinc supplements inhibited lesion development, although since no significant increase in lesion zinc levels was measured, this anti-atherosclerotic effect may be indirect. Copper, measured at low levels (?3 ppm) in the early lesion, is also depleted compared to the artery wall, suggesting that it is not a major factor in atherogenesis. Calcium is also depleted in early lesions, although at a later stage mineral deposition (hydroxyapatite) is observed to take place in the lesion/artery wall interface (intima), and subsequently in the lesion. These results are consistent with the hypotheses that iron plays a role in atherosclerosis probably through the production of free radicals and that zinc has an indirect protective effect. Copper appears to have a minor role due to its low lesion concentrations and hydroxyapatite deposition is a relatively late event.

  18. IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population

    PubMed Central

    Baragetti, Andrea; Garlaschelli, Katia; Pellegatta, Fabio; Grigore, Liliana; Norata, Giuseppe Danilo; Catapano, Alberico Luigi

    2015-01-01

    Inducible degrader of the low density lipoprotein receptor (IDOL), is an E3 ubiquitin ligase that negatively modulates low density lipoprotein receptor (LDL-R) expression. Genome-wide association studies (GWAS) indicated that genetic variants in IDOL gene contributes to variation in LDL-C plasma levels and the detailed analysis of a specific locus resulted in the identification of the functional common single nucleotide polymorphism (SNP) rs9370867 (c.G1025A, p.N342S) associates with increased LDL-R degradation and increased LDL-C levels. These findings, however, were not confirmed in two other independent cohorts and no data about the impact of this variant on atherosclerosis progression and cardiovascular risk are available. Aim of this study was to investigate the association between a functional variant in IDOL and atherosclerosis progression in an Italian general population. 1384 subjects enrolled in the PLIC study (Progression of Lesions in the Intima of Carotid) were genotyped by Q-PCR allelic discrimination and the association with anthropometric parameters, plasma lipids and the carotid intima media thickness (cIMT) and the impact on cardiovascular disease (CVD) incidence were investigated. The N342S variant was not associated with changes of the plasma lipid profile among GG, AG or AA carriers, including total cholesterol (249±21, 249±19 and 248±21 mg/dl respectively), LDL-C (158±25, 161±22 and 160±23 mg/dL), cIMT (0.74±0.14, 0.75±0.17 and 0.77±0.15 mm) and CVD incidence. In agreement, the expression of LDLR and the uptake of LDL was similar in macrophages derived from GG and AA carriers. Taken together our findings indicate that the N342S variant does not impact plasma lipid profile and is not associated with atherosclerosis progression and CVD in the general population, suggesting that other variants in the IDOL gene might be functionally linked with cholesterol metabolism. PMID:25927920

  19. IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population.

    PubMed

    Dhyani, Ashish; Tibolla, Gianpaolo; Baragetti, Andrea; Garlaschelli, Katia; Pellegatta, Fabio; Grigore, Liliana; Norata, Giuseppe Danilo; Catapano, Alberico Luigi

    2015-01-01

    Inducible degrader of the low density lipoprotein receptor (IDOL), is an E3 ubiquitin ligase that negatively modulates low density lipoprotein receptor (LDL-R) expression. Genome-wide association studies (GWAS) indicated that genetic variants in IDOL gene contributes to variation in LDL-C plasma levels and the detailed analysis of a specific locus resulted in the identification of the functional common single nucleotide polymorphism (SNP) rs9370867 (c.G1025A, p.N342S) associates with increased LDL-R degradation and increased LDL-C levels. These findings, however, were not confirmed in two other independent cohorts and no data about the impact of this variant on atherosclerosis progression and cardiovascular risk are available. Aim of this study was to investigate the association between a functional variant in IDOL and atherosclerosis progression in an Italian general population. 1384 subjects enrolled in the PLIC study (Progression of Lesions in the Intima of Carotid) were genotyped by Q-PCR allelic discrimination and the association with anthropometric parameters, plasma lipids and the carotid intima media thickness (cIMT) and the impact on cardiovascular disease (CVD) incidence were investigated. The N342S variant was not associated with changes of the plasma lipid profile among GG, AG or AA carriers, including total cholesterol (249±21, 249±19 and 248±21 mg/dl respectively), LDL-C (158±25, 161±22 and 160±23 mg/dL), cIMT (0.74±0.14, 0.75±0.17 and 0.77±0.15 mm) and CVD incidence. In agreement, the expression of LDLR and the uptake of LDL was similar in macrophages derived from GG and AA carriers. Taken together our findings indicate that the N342S variant does not impact plasma lipid profile and is not associated with atherosclerosis progression and CVD in the general population, suggesting that other variants in the IDOL gene might be functionally linked with cholesterol metabolism. PMID:25927920

  20. Porphyromonas gingivalis HSP60 peptides have distinct roles in the development of atherosclerosis.

    PubMed

    Jeong, Euikyong; Kim, Koanhoi; Kim, June Hong; Cha, Go Sim; Kim, Sung-Jo; Kang, Ho Sung; Choi, Jeomil

    2015-02-01

    Different epitope peptides of bacterial heat shock proteins may function as effector or regulatory molecules in autoimmune responses in infection-triggered atherosclerosis. We investigated the mechanisms for the distinct roles of two epitope peptides from Porphyromonas gingivalis heat shock protein 60 (HSP60) in atherogenesis with regard to peptide-specific T cell polarization relevant to (1) phenotype and cytokine profiles, (2) expression of transcription factors, and (3) role of antigen presenting dendritic cell subsets.Apolipoprotein E-knockout (ApoE KO) mice were immunized with peptide 14 or peptide 19 from P. gingivalis HSP60 prior to induction of atherosclerosis by infection with P. gingivalis plus a Western diet. Significant reductions in plaque/lipid droplet area and plasma cholesterol levels were observed in mice immunized with peptide 14, whereas the opposite phenomenon was evident in mice immunized with peptide 19. CD4+ T-cells polarized to the regulatory T-cell type in peptide 14-immunized group, whereas they polarized to the Th1 cells in peptide 19-immunized group; this observation was supported by the cytokine profiles characteristic to each T-cell phenotype.Significantly higher expression of Nr4a1 and Nr4a2 mRNA, transcriptional factors for regulatory T-cell type, were observed in peptide 14-immunized group. In contrast, the expression level of IFN-? and T-bet mRNA, signaling molecules for Th1 cells, was higher in peptide 19-immunized group than in PBS-immunized group.In non-immunized wild mice, BMDC-derived CD11c+ dendritic cells have shown to stimulate Tregs significantly in antigen-nonspecific manner. However, each peptide antigen demonstrated a unique mode of preferential adoption of dendritic cell subsets.In conclusion, peptide 14 or peptide 19 from P. gingivalis HSP60, respectively, may play either an anti- or pro-atherogenic role in the ApoE KO mouse model of infection-triggered atherosclerosis through distinct mechanisms operating in the polarization of T cells. PMID:25457882

  1. Antibodies against Native and Oxidized Cardiolipin and Phosphatidylserine and Phosphorylcholine in Atherosclerosis Development

    PubMed Central

    Frostegård, Anna G.; Su, Jun; Hua, Xiang; Vikström, Max; de Faire, Ulf; Frostegård, Johan

    2014-01-01

    Background Antibodies against cardiolipin and phosphatidylserine (anti-CL and anti-PS) are associated with thrombosis. In contrast, we determined that IgM antibodies against oxidized CL and PS (OxCL and OxPS) and phosphorylcholine (anti-PC) could be protection markers for cardiovascular disease (CVD). Methods 226 individuals with established hypertension (diastolic pressure>95 mmHg) from the European Lacidipine Study on Atherosclerosis. Antibodies were tested by ELISA. As a surrogate measure of atherosclerosis, the mean of the maximum intima-media thicknesses (IMT) in the far walls of common carotids and bifurcations was determined by ultrasonography at the time of inclusion and 4 years following inclusion. Results Increases in IMT measures at follow-up were significantly less common in subjects which at baseline had high IgM anti-OxPS and anti-PC at above 75th percentile: OR 0,45, CI (0,23–0,86) and OR 0.37, CI (0,19–0,71), p?=?0.0137 respectively and above 90th percentile: OR 0.32, CI (0,12–0,84) and OR 0.39, CI (0,15–1.00), p?=?0.050 and OR 0,22, CI (0,08–0,59) p?=?0,0029. IgM anti-OxCL was negatively associated with IMT increases (OR, 0.32, CI (0,12–0,84), p?=?0231). There were no associations for IgM anti-PS or anti-CL. Anti-PC, as determined herein by a commercial ELISA, was strongly associated with data from our previously published in house ELISA (R?=?0,87; p<0,0001).) Anti-PC was also a risk marker at low levels (below 25th percentile; OR?=?2,37 (1,16–4,82), p?=?0,0177). Conclusions High levels of IgM anti-OxPS and anti-OxCL, but not traditional anti-phospholipid antibodies (anti-PS and anti-CL), are associated with protection against atherosclerosis development. In addition, low IgM anti-PC was a risk marker but high a protection marker. PMID:25473948

  2. 56Fe accelerates development of atherosclerosis in apoE -/-mice

    NASA Astrophysics Data System (ADS)

    Kucik, Dennis; Yu, Tao; Parks, Brian; Yu, Shaohua; Srivastava, Roshni; Gupta, Kiran; Wu, Xing; Khaled, Saman; Chang, Polly; Kabarowski, Janusz

    Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. For example, for women with early breast cancer, the benefit of radiotherapy can be nearly offset by the increased risk of mortality from cardiovascular disease. Head and neck cancer patients who undergo radiation treatment are at significantly elevated risk of stroke, even in a relatively young patient population that would not normally be at risk for atheroscle-rosis. Similarly, atomic bomb survivors had an increased incidence of mortality from coronary artery disease and stroke. Even radiation technologists working before 1950 (when occupational exposure was higher) had increased mortality due to circulatory diseases. Although much is known about the cardiovascular consequences these exposures to X-raus and gamma radiation, the response to the type of radiation likely to be encountered in prolonged space flight has not been determined. A key component of this cosmic radiation is 56Fe, which is particularly damaging to tissues. Using collimated beams, we selectively irradiated aortic arches and carotids (only) of the well-established apoE -/-atherosclerosis mouse model to test directly whether 56Fe exposure is a cardiovascular risk factor. Mice were sacrificed at 13 weeks post-irradiation and dissected, and aortas were divided into areas that had been targeted by the ion beam and those that were not. The area that was covered by plaques was then quantified. Plaque area at 13 weeks post-irradiation was significantly greater in targeted areas of mice that had received 5 Gy of 56Fe as compared to age-and sex-matched un-irradiated controls. In the carotid arteries and aortic roots, significantly greater atherosclerosis was apparent for a 2Gy exposure as well (the lowest dose tested). This demonstrates that even a single exposure to heavy ion radiation is capable of triggering events that culminate in cardiovascular disease, even long after the exposure has ended. There-fore, the potential consequences of radiation exposure for astronaut health on missions beyond Earth orbit represent a risk that warrants further investigation. Current studies are aimed at better understanding the magnitude of this risk and the molecular mechanism, which will be essential to devising the countermeasures that may be necessary to ensure astronaut safety in future missions.

  3. Overexpression of CRY1 protects against the development of atherosclerosis via the TLR/NF-?B pathway.

    PubMed

    Yang, Lei; Chu, Yingjie; Wang, Long'an; Wang, Yuhang; Zhao, Xiangmei; He, Wenqi; Zhang, Peirong; Yang, Xianzhi; Liu, Xiaoyu; Tian, Lixiao; Li, Bing; Dong, Shujuan; Gao, Chuanyu

    2015-09-01

    It has been demonstrated that the circadian clock system could be a potential factor involved in inflammation and the progression of atherosclerosis. A previous study has reported that cryptochrome 1 (CRY1), which is a core clock component, is associated with regulating proinflammation. However, whether CRY1 is involved in atherosclerosis is currently unknown. In the present study, we aimed to explore the role of CRY1 in regulating atherosclerosis in apolipoprotein E (ApoE)-deficient mice and the underlying molecular mechanism. We found that CRY1 mRNA expression was significantly decreased in atherosclerotic patients compared to the healthy subjects. Overexpression of CRY1 in the mouse model of atherosclerosis by adenovirus-mediated gene transfer significantly decreased the expression of proinflammatory factors including tumor necrosis factor-? (TNF-?), interleukin (IL)-1, IL-6, and macrophage inflammatory protein-1? (MIP-1?). In addition, the adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin, were also downregulated by CRY1 overexpression. Furthermore, the plaque area of the aortic sinus and the concentrations of total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) were also decreased in the atherosclerotic mice by CRY1 overexpression. Moreover, overexpression of CRY1 significantly decreased the protein levels of toll-like receptor (TLR) 2, TLR4 and phosphorylated p65 (p-p65). Additionally, the results of luciferase reporter assay exhibited that CRY1 overexpression was capable of inhibiting the activation of nuclear factor-kappa B (NF-?B). Taken together, our results suggest that overexpression of CYR1 relieves the development of atherosclerosis that may be associated with regulating the TLR/NF-?B pathway. PMID:26218278

  4. A Dietary Mixture Containing Fish Oil, Resveratrol, Lycopene, Catechins, and Vitamins E and C Reduces Atherosclerosis in Transgenic Mice123

    PubMed Central

    Verschuren, Lars; Wielinga, Peter Y.; van Duyvenvoorde, Wim; Tijani, Samira; Toet, Karin; van Ommen, Ben; Kooistra, Teake; Kleemann, Robert

    2011-01-01

    Chronic inflammation and proatherogenic lipids are important risk factors of cardiovascular disease (CVD). Specific dietary constituents such as polyphenols and fish oils may improve cardiovascular risk factors and may have a beneficial effect on disease outcomes. We hypothesized that the intake of an antiinflammatory dietary mixture (AIDM) containing resveratrol, lycopene, catechin, vitamins E and C, and fish oil would reduce inflammatory risk factors, proatherogenic lipids, and endpoint atherosclerosis. AIDM was evaluated in an inflammation model, male human C-reactive protein (CRP) transgenic mice, and an atherosclerosis model, female ApoE*3Leiden transgenic mice. Two groups of male human-CRP transgenic mice were fed AIDM [0.567% (wt:wt) powder and 0.933% (wt:wt oil)] or placebo for 6 wk. The effects of AIDM on basal and IL-1?–stimulated CRP expression were investigated. AIDM reduced cytokine-induced human CRP and fibrinogen expression in human-CRP transgenic mice. In the atherosclerosis study, 2 groups of female ApoE*3Leiden transgenic mice were fed an atherogenic diet supplemented with AIDM [0.567% (wt:wt) powder and 0.933% (wt:wt oil)] or placebo for 16 wk. AIDM strongly reduced plasma cholesterol, TG, and serum amyloid A concentrations compared with placebo. Importantly, long-term treatment of ApoE*3Leiden mice with AIDM markedly reduced the development of atherosclerosis by 96% compared with placebo. The effect on atherosclerosis was paralleled by a reduced expression of the vascular inflammation markers and adhesion molecules inter-cellular adhesion molecule-1 and E-selectin. Dietary supplementation of AIDM improves lipid and inflammatory risk factors of CVD and strongly reduces atherosclerotic lesion development in female transgenic mice. PMID:21411607

  5. A PIM? analogue suppresses allergic airway disease.

    PubMed

    Harper, Jacquie L; Hayman, Colin M; Larsen, David S; Painter, Gavin F; Singh-Gill, Gurmit

    2011-01-15

    Two approaches for the synthesis of a phosphatidylinositol dimannoside (PIM?) analogue 4 that mimics the suppressive activity of natural PIMs and also synthetic PIM? have been developed. This analogue, where the inositol core was replaced by glycerol, was tested for its ability to suppress cellular inflammation in a mouse model of allergic asthma and shown to be effective in suppressing airway eosinophilia. Suppression of all inflammatory cells monitored was observed, indicating a general blockade of cellular activity. These data indicate that the inositol core is not essential for this suppressive activity. PMID:21215641

  6. Background Suppression Effects on Signal Estimation

    SciTech Connect

    Burr, Tom

    2008-01-01

    Gamma detectors at border crossings are intended to detect illicit nuclear material. One performance challenge involves the fact that vehicles suppress the natural background, thus potentially reducing detection probability for threat items. Methods to adjust for background suppression have been considered in related but different settings. Here, methods to adjust for background suppression are tested in the context of signal estimation. Adjustment methods include several clustering options. We find that for the small-to-moderate suppression magnitudes exhibited in the analyzed data, suppression adjustment is only moderatel helpful in locating the signal peak, and in estimating its width or magnitude.

  7. Molecular histology of arteries: mass spectrometry imaging as a novel ex vivo tool to investigate atherosclerosis.

    PubMed

    Martin-Lorenzo, Marta; Alvarez-Llamas, Gloria; McDonnell, Liam A; Vivanco, Fernando

    2016-01-01

    Atherosclerosis is usually the underlying cause of a fatal event such as myocardial infarction or ictus. The atherome plaque develops silently and asymptomatically within the arterial intima layer. In this context, the possibility to analyze the molecular content of arterial tissue while preserving each molecule's specific localization is of great interest as it may reveal further insights into the physiopathological changes taking place. Mass spectrometry imaging (MSI) enables the spatially resolved molecular analysis of proteins, peptides, metabolites, lipids and drugs directly in tissue, with a resolution sufficient to reveal molecular features specific to distinct arterial structures. MSI represents a novel ex vivo imaging tool still underexplored in cardiovascular diseases. This review focuses on the MSI technique applied to cardiovascular disease and covers the main contributions to date, ongoing efforts, the main challenges and current limitations of MSI. PMID:26558814

  8. Adipose tissue transplantation may be a potential treatment for diabetes, atherosclerosis and nonalcoholic steatohepatitis.

    PubMed

    Sanal, Madhusudana Girija

    2009-03-01

    Adipose tissue is critical in energy homeostasis. Adipose tissue 'buffers' the lipids and energy rich compounds which are pumped into the blood stream soon after meals. It senses, signals other organs like liver and brain about the energy reserves via adipokines. Adiponectin, the most abundant adipokine has insulin sensitizing, anti-inflammatory antiatherogenic and antisteatotic effects. Adipose tissue dysfunction is accompanied by abnormal lipid distribution and storage which contributes to diseases like diabetes, nonalcoholic fatty liver disease and atherosclerosis. Obesity and lipodystrophy are associated with dysfunctional adipocytes. Pre-adipocytes are easy to isolate and culture. A personalized depot specific liposuction to remove the inactive adipocytes followed by adipocyte repopulation could be useful in the treatment of these diseases. PMID:19046821

  9. Atherosclerosis, oxidative stress and auto-antibodies in systemic lupus erythematosus and primary antiphospholipid syndrome.

    PubMed

    Alves, Jose D; Ames, Paul R J

    2003-01-01

    Overwhelming evidence spanning three decades has consistently shown that coronary artery disease is a major cause of morbidity and mortality in Systemic Lupus Erythematosus. Traditionally this was explained by abnormalities of the lipid profile induced by prolonged steroid treatment. Subsequently, antiphospholipid antibodies were presented as an additional cardiovascular risk factor. Recently, antibodies towards high-density lipoprotein and antiapolipoprotein A-I have been identified. These, together with anti-beta2 glycoprotein-1, interfere with the major antioxidant defence of patients with SLE and with primary antiphospholiqid syndrome exposing them to the atherogenic potential of enhanced oxidative stress. The present review discusses how the latter auto-antibodies, together with abnormalities of their target lipid auto-antigens, could enhance the risk of atherosclerosis in SLE and APS. PMID:12638899

  10. RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling.

    PubMed

    Patel, Jyoti; McNeill, Eileen; Douglas, Gillian; Hale, Ashley B; de Bono, Joseph; Lee, Regent; Iqbal, Asif J; Regan-Komito, Daniel; Stylianou, Elena; Greaves, David R; Channon, Keith M

    2015-01-01

    Chemokine signalling drives monocyte recruitment in atherosclerosis and aortic aneurysms. The mechanisms that lead to retention and accumulation of macrophages in the vascular wall remain unclear. Regulator of G-Protein Signalling-1 (RGS1) deactivates G-protein signalling, reducing the response to sustained chemokine stimulation. Here we show that Rgs1 is upregulated in atherosclerotic plaque and aortic aneurysms. Rgs1 reduces macrophage chemotaxis and desensitizes chemokine receptor signalling. In early atherosclerotic lesions, Rgs1 regulates macrophage accumulation and is required for the formation and rupture of Angiotensin II-induced aortic aneurysms, through effects on leukocyte retention. Collectively, these data reveal a role for Rgs1 in leukocyte trafficking and vascular inflammation and identify Rgs1, and inhibition of chemokine receptor signalling as potential therapeutic targets in vascular disease. PMID:25782711

  11. Coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC) study.

    PubMed

    Chambless, Lloyd E; Folsom, Aaron R; Sharrett, A Richey; Sorlie, Paul; Couper, David; Szklo, Moyses; Nieto, F Javier

    2003-09-01

    Risk prediction functions for incident coronary heart disease (CHD) were estimated using data from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective study of CHD in 15,792 persons recruited in 1987-1989 from four U.S. communities, with follow-up through 1998. Predictivity of which individuals had incident CHD was assessed by increase in area under ROC curves resulting from adding nontraditional risk factors and markers of subclinical disease to a basic model containing only traditional risk factors. We also assessed the increase in population attributable risk. The additional factors were body mass index; waist-hip ratio; sport activity index; forced expiratory volume; plasma fibrinogen, factor VIII, von Willebrand factor, and Lp(a); heart rate; Keys score; pack-years smoking; and subclinical disease marker carotid intima-media thickness. These factors substantially improved prediction of future CHD for men, less for women, and also increased attributable risks. PMID:14505774

  12. Occupation and the Prevalence of Respiratory Health Symptoms and Conditions: The Atherosclerosis Risk in Communities Study

    PubMed Central

    Mirabelli, Maria C.; London, Stephanie J.; Charles, Luenda E.; Pompeii, Lisa A.; Wagenknecht, Lynne E.

    2011-01-01

    Objectives To examine associations between occupation and respiratory health in a large, population-based cohort of adults in the United States. Methods Data from 15,273 participants, aged 45-64 years, in the Atherosclerosis Risk in Communities (ARIC) study were used to examine associations of current or most recent job held with the prevalence of self-reported chronic cough, chronic bronchitis, wheeze, asthma, and measures of lung function collected by spirometry. Results Eleven percent of participants reported wheeze and 9% were classified as having airway obstruction. Compared to individuals in managerial and administrative jobs, increased prevalences of respiratory outcomes were observed among participants in selected occupations, including construction and extractive trades (wheeze: prevalence ratio [PR]: 1.92, 95% confidence interval [CI]: 1.35, 2.73; airway obstruction: PR: 1.31, 95% CI: 1.05, 1.65). Conclusions Specific occupations are associated with adverse respiratory health. PMID:22157701

  13. Bifurcation and dynamics in a mathematical model of early atherosclerosis : How acute inflammation drives lesion development.

    PubMed

    Chalmers, Alexander D; Cohen, Anna; Bursill, Christina A; Myerscough, Mary R

    2015-12-01

    We present here a mathematical model describing the primary mechanisms that drive the early stages of atherosclerosis. This involves the interactions between modified low density lipoprotein (LDL), monocytes/macrophages, cytokines and foam cells. This model suggests that there is an initial inflammatory phase associated with atherosclerotic lesion development and a longer, quasi-static process of plaque development inside the arterial wall that follows the initial transient. We will show results that show how different LDL concentrations in the blood stream and different immune responses can affect the development of a plaque. Through numerical bifurcation analysis, we show the existence of a fold bifurcation when the flux of LDL from the blood is sufficiently high. By analysing the model presented in this paper, we gain a greater insight into this inflammatory response qualitatively and quantitatively. PMID:25732771

  14. A novel fluorescent probe for the detection of myeloperoxidase activity in atherosclerosis-associated macrophages

    PubMed Central

    Shepherd, Joanna; Hilderbrand, Scott A.; Waterman, Peter; Heinecke, Jay W.; Weissleder, Ralph; Libby, Peter

    2009-01-01

    SUMMARY The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl/OCl?) is implicated in the pathogenesis of atherosclerosis and other inflammatory states. We have synthesized a novel imaging probe, sulfonaphthoaminophenyl fluorescein (SNAPF), that selectively reacts to HOCl. SNAPF detects HOCl produced by stimulated MPO-expressing cells cultured from human whole blood, as well as HOCl from bone marrow (BM)-derived macrophages isolated from transgenic mice that express human MPO. Two lines of evidence indicate that SNAPF permits the in vivo imaging of HOCl production. First, we used this approach to demonstrate HOCl production by neutrophils in experimental murine peritonitis. Second, we detected HOCl production by MPO expressing cells in human atherosclerotic arteries. Thus, fluorescence reflectance imaging by SNAPF may provide a valuable non-invasive molecular imaging tool for implicating HOCl and MPO in the damage of inflamed tissues. PMID:18022561

  15. [Etiology of atherosclerosis--special reference to humoral and neurogenic factors].

    PubMed

    Kishida, Ken; Funahashi, Tohru

    2011-01-01

    Atherosclerotic cardiovascular diseases, currently the leading cause of death and illness in developed countries, will soon become the health problem worldwide. Atherosclerosis, a progressive disease characterized by the accumulation of lipids and fibrous elements in the arteries, constitutes the most important contributor to this growing burden of cardiovascular disease. The vascular endothelium is the inner lining of all blood vessels and serves as an important autocrine and paracrine organ, that regulates vascular wall functions. The vascular components are susceptible to the effect of oxidative stress, inflammation, (adipo)cytokines, neurohumoral factors, sleep disorders, psychogenic stress and other mediators. These vascular systems should maintain vascular homeostasis in the whole body for preventing atherosclerotic cardiovascular diseases. PMID:21226258

  16. Quantitative trait locus analysis of susceptibility to diet-induced atherosclerosis in recombinant inbred mice

    SciTech Connect

    Hyman, R.W.; Frank, S.; Warden, C.H.

    1994-12-01

    Quantitative trait locus (QTL) analysis is a statistical method that can be applied to identify loci making a significant impact on a phenotype. For the phenotype of susceptibility to diet-induced atherosclerosis in the mouse, we have studied four quantitative traits: area of aortic fatty streaks and serum concentrations of high-density lipoprotein-bound cholesterol (HDL-cholesterol), apolipoprotein A-I, and apolipoprotein A-II (apo A-II). QTL analysis revealed a significant locus on chromosome 1 distal impacting serum apo A-II concentration on a high-fat diet and serum HDL-cholesterol concentration on a chow diet. This locus is presumably Apoa-2, the structural gene for apo A-II. QTL analysis of aortic fatty streaks failed to reveal a significant locus. 19 refs., 3 tabs.

  17. RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling

    PubMed Central

    Patel, Jyoti; McNeill, Eileen; Douglas, Gillian; Hale, Ashley B.; de Bono, Joseph; Lee, Regent; Iqbal, Asif J.; Regan-Komito, Daniel; Stylianou, Elena; Greaves, David R.; Channon, Keith M.

    2015-01-01

    Chemokine signalling drives monocyte recruitment in atherosclerosis and aortic aneurysms. The mechanisms that lead to retention and accumulation of macrophages in the vascular wall remain unclear. Regulator of G-Protein Signalling-1 (RGS1) deactivates G-protein signalling, reducing the response to sustained chemokine stimulation. Here we show that Rgs1 is upregulated in atherosclerotic plaque and aortic aneurysms. Rgs1 reduces macrophage chemotaxis and desensitizes chemokine receptor signalling. In early atherosclerotic lesions, Rgs1 regulates macrophage accumulation and is required for the formation and rupture of Angiotensin II-induced aortic aneurysms, through effects on leukocyte retention. Collectively, these data reveal a role for Rgs1 in leukocyte trafficking and vascular inflammation and identify Rgs1, and inhibition of chemokine receptor signalling as potential therapeutic targets in vascular disease. PMID:25782711

  18. Kidney Function, Endothelial Activation and Atherosclerosis in Black and White Africans with Rheumatoid Arthritis

    PubMed Central

    Dessein, Patrick H.; Hsu, Hon-Chun; Tsang, Linda; Millen, Aletta M. E.; Woodiwiss, Angela J.; Norton, Gavin R.; Solomon, Ahmed; Gonzalez-Gay, Miguel A.

    2015-01-01

    Objective To determine whether kidney function independently relates to endothelial activation and ultrasound determined carotid atherosclerosis in black and white Africans with rheumatoid arthritis (RA). Methods We calculated the Jelliffe, 5 Cockcroft-Gault equations, Salazar-Corcoran, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (EGFR) equations in 233 (112 black) RA patients. Results The CKD-EPI eGFR was <90 ml/min/1.73m2 in 49.1% and 30.6% of black and white patients, respectively (odds ratio (95% confidence interval) = 2.19 (1.28–3.75), p = 0.004). EGFRs were overall consistently associated with monocyte chemoattractant protein-1 and angiopoietin 2 concentrations in white patients, and with carotid intima-media thickness and plaque in black participants. Amongst black patients, plaque prevalence was 36.7% and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was not associated with plaque presence for the MDRD equation (p = 0.3), whereas the respective relationship was significant or borderline significant (p = 0.003 to 0.08) and of similar extent (p>0.1 for comparisons of AUC (SE)) for the other 8 equations. Based on optimal eGFR cutoff values with sensitivities and specificities ranging from 42 to 60% and 70 to 91% respectively, as determined in ROC curve analysis, a low eGFR increased the odds ratio for plaque 2.2 to 4.0 fold. Conclusion Reduced kidney function is independently associated with atherosclerosis and endothelial activation in black and white Africans with RA, respectively. CKD is highly prevalent in black Africans with RA. Apart from the MDRD, eGFR equations are useful in predicting carotid plaque presence, a coronary heart disease equivalent, amongst black African RA patients. PMID:25806966

  19. Retinol Binding Protein 4 Concentrations Relate to Enhanced Atherosclerosis in Obese Patients with Rheumatoid Arthritis

    PubMed Central

    Dessein, Patrick H.; Tsang, Linda; Norton, Gavin R.; Woodiwiss, Angela J.; Solomon, Ahmed

    2014-01-01

    Background Retinol binding protein 4 (RBP) enhances metabolic risk and atherogenesis. Whether RBP4 contributes to cardiovascular risk in rheumatoid arthritis (RA) is unknown. Methods We assessed RBP4 concentrations and those of endothelial activation molecules including E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 by ELISA, and the common carotid artery intima-media thickness (cIMT) and carotid artery plaque by ultrasound in 217 (112 black and 105 white) patients with RA. Relationships were identified in potential confounder and mediator adjusted mixed regression models. Results RBP4 concentrations were associated with systolic and mean blood pressure, and those of glucose and E-selectin (partial R?=??0.207 (p?=?0.003), ?0.195 (p?=?0.006), ?0.155 (p?=?0.03) and ?0.191 (p?=?0.007), respectively in all patients); these RBP4-cardiovascular risk relations were mostly reproduced in patients with but not without adverse traditional or non-traditional cardiovascular risk profiles. RBP4 concentrations were not associated with atherosclerosis in all patients, but related independently to cIMT (partial R?=?0.297, p?=?0.03) and plaque (OR (95%CI)?=?2.95 (1.31–6.68), p?=?0.008) in those with generalized obesity, as well as with plaque in those with abdominal obesity (OR (95%CI)?=?1.95 (1.12–3.42), p?=?0.01). Conclusion In the present study, RBP4 concentrations were inversely associated with metabolic risk and endothelial activation in RA. This requires further investigation. RBP4 concentrations were related to enhanced atherosclerosis in patients with generalized or/and abdominal obesity. PMID:24651174

  20. Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women123

    PubMed Central

    Mozaffarian, Dariush; Rimm, Eric B; Herrington, David M

    2005-01-01

    Background: The influence of diet on atherosclerotic progression is not well established, particularly in postmenopausal women, in whom risk factors for progression may differ from those for men. Objective: The objective was to investigate associations between dietary macronutrients and progression of coronary atherosclerosis among postmenopausal women. Design: Quantitative coronary angiography was performed at baseline and after a mean follow-up of 3.1 y in 2243 coronary segments in 235 postmenopausal women with established coronary heart disease. Usual dietary intake was assessed at baseline. Results: The mean (±SD) total fat intake was 25 ± 6% of energy. In multivariate analyses, a higher saturated fat intake was associated with a smaller decline in mean minimal coronary diameter (P = 0.001) and less progression of coronary stenosis (P =0.002) during follow-up. Compared with a 0.22-mm decline in the lowest quartile of intake, there was a 0.10-mm decline in the second quartile (P = 0.002), a 0.07-mm decline in the third quartile (P = 0.002), and no decline in the fourth quartile (P <0.001); P for trend =0.001. This inverse association was more pronounced among women with lower monounsaturated fat (P for interaction =0.04) and higher carbohydrate (P for interaction =0.004) intakes and possibly lower total fat intake (P for interaction =0.09). Carbohydrate intake was positively associated with atherosclerotic progression (P =0.001), particularly when the glycemic index was high. Polyunsaturated fat intake was positively associated with progression when replacing other fats (P = 0.04) but not when replacing carbohydrate or protein. Monoun-saturated and total fat intakes were not associated with progression. Conclusions: In postmenopausal women with relatively low total fat intake, a greater saturated fat intake is associated with less progression of coronary atherosclerosis, whereas carbohydrate intake is associated with a greater progression. PMID:15531663