Sample records for irbesartan suppressing atherosclerosis

  1. Molecular mechanisms of irbesartan suppressing atherosclerosis in high cholesterol-diet apolipoprotein E knock-out mice

    Microsoft Academic Search

    Rui Yao; Xiang Cheng; Yong Chen; Jiang-Jiao Xie; Xian Yu; Meng-Yang Liao; Ying-Jun Ding; Ting-Ting Tang; Yu-Hua Liao

    2010-01-01

    ObjectiveAtherosclerosis is a chronic inflammatory disease in which the renin–angiotensin–aldosterone system plays an important role. Evidence indicate that the angiotensin type 1 receptor blockers can suppress atherogenesis, but the exact mechanisms have not been fully elucidated. The study was undertaken to investigate the potential effects and molecular mechanisms of an angiotensin type 1 receptor blocker irbesartan on atherogenesis in high

  2. Atherosclerosis

    Microsoft Academic Search

    Edward M Boyle; Sean T Lille; Eric Allaire; Alexander W Clowes; Edward D Verrier

    1997-01-01

    Most of the indications for cardiovascular operation and many of its complications are in large part due to advanced atherosclerosis. The pathogenesis of atherosclerosis involves inflammatory infiltration of the vessel wall, cellular proliferation, fibrous plaque formation, and ultimately plaque rupture and occlusive thrombosis. Many of these events are linked, at least initially, to chronic injury of the vascular endothelium. Endothelial

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

    SciTech Connect

    Kinoshita, Hiroyuki [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Ishii, Norio; Fukuda, Kazuki; Senokuchi, Takafumi; Motoshima, Hiroyuki; Kondo, Tatsuya; Taketa, Kayo; Kawasaki, Shuji; Hanatani, Satoko [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Takeya, Motohiro [Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Nishikawa, Takeshi; Araki, Eiichi [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)

    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.

  4. Effects of Ang II Receptor Blocker Irbesartan on Adipose Tissue Function in Mice with Metabolic Disorders

    PubMed Central

    Maeda, Akinobu; Tamura, Kouichi; Wakui, Hiromichi; Ohsawa, Masato; Azushima, Kengo; Uneda, Kazushi; Kobayashi, Ryu; Tsurumi-Ikeya, Yuko; Kanaoka, Tomohiko; Dejima, Toru; Ohki, Koji; Haku, Sona; Yamashita, Akio; Umemura, Satoshi

    2014-01-01

    Recent studies indicate that the functional renin-angiotensin system (RAS) exists in the adipose tissue. The adipose tissue RAS is proposed in the pathophysiology of metabolic disorders. In the present study, we examined therapeutic effects of irbesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders without any dietary loading, with our focus on the analysis on possible effect of irbesartan on the adipose tissue. The treatment with irbesartan significantly lowered systolic blood pressure with a concomitant decrease in body weight in KKAy mice. In addition, irbesartan significantly decreased the adipose leptin mRNA expression and tended to decrease IL-6 mRNA expression in the adipose tissue of KKAy mice. Furthermore irbesartan preserved the adipose gene expression of AT1R-associated protein (ATRAP), an endogenous inhibitory molecule of tissue AT1R signaling, with a concomitant tendency of up-regulation of adipose tissue ATRAP/AT1R ratio. Collectively, these results suggest that the irbesartan-induced beneficial suppressive effect on the leptin-IL-6 axis in the adipose tissue in KKAy mice is partly mediated by a trend of up-regulation of the adipose ATRAP/AT1R ratio as one of pleiotropic effects of irbesartan. PMID:24834011

  5. Effects of Ang II receptor blocker irbesartan on adipose tissue function in mice with metabolic disorders.

    PubMed

    Maeda, Akinobu; Tamura, Kouichi; Wakui, Hiromichi; Ohsawa, Masato; Azushima, Kengo; Uneda, Kazushi; Kobayashi, Ryu; Tsurumi-Ikeya, Yuko; Kanaoka, Tomohiko; Dejima, Toru; Ohki, Koji; Haku, Sona; Yamashita, Akio; Umemura, Satoshi

    2014-01-01

    Recent studies indicate that the functional renin-angiotensin system (RAS) exists in the adipose tissue. The adipose tissue RAS is proposed in the pathophysiology of metabolic disorders. In the present study, we examined therapeutic effects of irbesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders without any dietary loading, with our focus on the analysis on possible effect of irbesartan on the adipose tissue. The treatment with irbesartan significantly lowered systolic blood pressure with a concomitant decrease in body weight in KKAy mice. In addition, irbesartan significantly decreased the adipose leptin mRNA expression and tended to decrease IL-6 mRNA expression in the adipose tissue of KKAy mice. Furthermore irbesartan preserved the adipose gene expression of AT1R-associated protein (ATRAP), an endogenous inhibitory molecule of tissue AT1R signaling, with a concomitant tendency of up-regulation of adipose tissue ATRAP/AT1R ratio. Collectively, these results suggest that the irbesartan-induced beneficial suppressive effect on the leptin-IL-6 axis in the adipose tissue in KKAy mice is partly mediated by a trend of up-regulation of the adipose ATRAP/AT1R ratio as one of pleiotropic effects of irbesartan. PMID:24834011

  6. Pharmacologic Suppression of Hepcidin Increases Macrophage Cholesterol Efflux and Reduces Foam Cell Formation and Atherosclerosis

    PubMed Central

    Saeed, Omar; Otsuka, Fumiyuki; Polavarapu, Rohini; Karmali, Vinit; Weiss, Daiana; Davis, Talina; Rostad, Brad; Pachura, Kimberly; Adams, Lila; Elliott, John; Taylor, W. Robert; Narula, Jagat; Kolodgie, Frank; Virmani, Renu; Hong, Charles C.; Finn, Aloke V.

    2012-01-01

    Objectives We recently reported that lowering of macrophage free intracellular iron increases expression of cholesterol efflux transporters ABCA1 and ABCG1 by reducing generation of reactive oxygen species. In this study, we explore whether reducing macrophage intracellular iron levels via pharmacologic suppression of hepcidin can increase macrophage-specific expression of cholesterol efflux transporters and reduce atherosclerosis. Methods and Results To suppress hepcidin, increase expression of the iron exporter ferroportin (FPN), and reduce macrophage intracellular iron, we used a small molecule inhibitor of BMP signaling, LDN 193189 (LDN). LDN (10 mg/kg i.p. bid) was administered to mice and its effects on atherosclerosis, intracellular iron, oxidative stress, lipid efflux, and foam cell formation were measured in plaques and peritoneal macrophages. Long-term LDN administration to Apo E (-/-) mice increased ABCA1 immunoreactivity within intraplaque macrophages by 3.7-fold (n=8; p=0.03), reduced oil-red-o positive lipid area by 50% (n=8; p=0.02) and decreased total plaque area by 43% (n=8; p=0.001). LDN suppressed liver hepcidin transcription and increased macrophage FPN, lowering intracellular iron and hydrogen peroxide production. LDN treatment increased macrophage ABCA1 and ABCG1 expression, significantly raised cholesterol efflux to ApoA-1 and decreased foam cell formation. All preceding LDN-induced effects on cholesterol efflux were reversed by exogenous hepcidin administration, suggesting that modulation of intracellular iron levels within macrophages as the mechanism by which LDN triggers these effects. Conclusion These data suggest that pharmacologic manipulation of iron homeostasis may be a promising target to increase macrophage reverse cholesterol transport and limit atherosclerosis. PMID:22095982

  7. Inhibiting DNA Methylation by 5-Aza-2?-deoxycytidine Ameliorates Atherosclerosis Through Suppressing Macrophage Inflammation

    PubMed Central

    Cao, Qiang; Wang, Xianfeng; Jia, Lin; Mondal, Ashis K.; Diallo, Abdoulaye; Hawkins, Gregory A.; Das, Swapan K.; Parks, John S.; Yu, Liqing; Shi, Huidong

    2014-01-01

    Inflammation marks all stages of atherogenesis. DNA hypermethylation in the whole genome or specific genes is associated with inflammation and cardiovascular diseases. Therefore, we aimed to study whether inhibiting DNA methylation by DNA methyltransferase inhibitor 5-aza-2?-deoxycytidine (5-aza-dC) ameliorates atherosclerosis in low-density lipoprotein receptor knockout (Ldlr?/?) mice. Ldlr?/? mice were fed an atherogenic diet and adminisered saline or 5-aza-dC (0.25 mg/kg) for up to 30 weeks. 5-aza-dC treatment markedly decreased atherosclerosis development in Ldlr?/? mice without changes in body weight, plasma lipid profile, macrophage cholesterol levels and plaque lipid content. Instead, this effect was associated with decreased macrophage inflammation. Macrophages with 5-aza-dC treatment had downregulated expression of genes involved in inflammation (TNF-?, IL-6, IL-1?, and inducible nitric oxidase) and chemotaxis (CD62/L-selectin, chemokine [C-C motif] ligand 2/MCP-1 [CCL2/MCP-1], CCL5, CCL9, and CCL2 receptor CCR2). This resulted in attenuated macrophage migration and adhesion to endothelial cells and reduced macrophage infiltration into atherosclerotic plaques. 5-aza-dC also suppressed macrophage endoplasmic reticulum stress, a key upstream signal that activates macrophage inflammation and apoptotic pathways. Finally, 5-aza-dC demethylated liver X receptor ? (LXR?) and peroxisome proliferator-activated receptor ?1 (PPAR?1) promoters, which are both enriched with CpG sites. This led to overexpression of LXR? and PPAR?, which may be responsible for 5-aza-dC's anti-inflammatory and atheroprotective effect. Our findings provide strong evidence that DNA methylation may play a significant role in cardiovascular diseases and serve as a therapeutic target for prevention and treatment of atherosclerosis. PMID:25251587

  8. Irbesartan

    MedlinePLUS

    ... a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 ... Do not use salt substitutes containing potassium without talking to your doctor. If your doctor prescribes a low-salt or low-sodium diet, ...

  9. Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts

    Microsoft Academic Search

    Lisa Park; Kathleen G. Raman; Kenneth J. Lee; Yan Lu; Luis J. Ferran; Wing Sun Chow; David Stern; Ann Marie Schmidt

    1998-01-01

    Accelerated atherosclerosis in patients with diabetes is a major cause of their morbidity and mortality, and it is unresponsive to therapy aimed at restoring relative euglycemia. In hyperglycemia, nonenzymatic glycation and oxidation of proteins and lipids results in the accumulation of irreversibly formed advanced glycation endproducts. These advanced glycation endproducts engage their receptor in cells of the blood vessel wall,

  10. Investigation of RNA interference suppression of matrix metalloproteinase-9 in mouse model of atherosclerosis

    PubMed Central

    Jin, Zhe-Xiu; Xiong, Qiang; Jia, Fang; Sun, Chun-Ling; Zhu, Hong-Tao; Ke, Fu-Sheng

    2015-01-01

    Objective: To investigate the effect of RNA interference of matrix metalloproteinase (MMP)-9 on atherosclerosis on atherosclerosis in apolipoprotein E (ApoE)-/- mouse. Methods: ApoE-/- mouse strain and three cell lines (293T, NIH3T3 and Raw264.7) were used in the present study to investigate the effect of MMP-9 silencing by RNA interference. Thirty 10-week-old ApoE-/- mice were randomly assigned to a control group, lentiviruses with naked vector group and Lentiviruses-MMP-9 intervention group (n = 10). Aortic atherosclerotic plaques of the mice were stained with immunohistochemical techniques, the MMP-9 and high-sensitivity C-reactive protein levels of three groups were detected simultaneously. Expression of MMP-9 was significantly down-regulated in interference group. MMP-9 and high-sensitivity C-reactive protein levels in MMP-9 interference group were significantly lower than that of the control group. Conclusion: The expression of MMP-9 is closely related to vulnerability of atherosclerotic plaques. Silencing of MMP-9 expression acts as a positive role in maintenance of atherosclerotic plaque stability. The present study provides novel experimental insight for the treatment of vulnerable plaques in atherosclerosis.

  11. Acidic Polysaccharide Extracts from Gastrodia Rhizomes Suppress the Atherosclerosis Risk Index through Inhibition of the Serum Cholesterol Composition in Sprague Dawley Rats Fed a High-Fat Diet

    PubMed Central

    Kim, Kui-Jin; Lee, Ok-Hwan; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

    2012-01-01

    Obesity is associated with a broad spectrum of cardio-metabolic disturbances, including atherosclerosis and cardiovascular disease (CDV). A high-fat diet has been shown to cause an elevation of the plasma cholesterol levels in humans, and the control of serum cholesterol has been demonstrated to be important in the prevention of CVD and atherosclerosis. The aims of this study were to demonstrate that crude and acidic polysaccharide extracts from Gastrodia rhizomes suppress atherosclerosis through the regulation of serum lipids in Sprague Dawley (SD) rats fed a high-fat diet. We examined the concentrations of serum lipids, including total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and low-density lipoproteins (LDL) cholesterol, in SD rats fed a high-fat diet and evaluated the atherogenic index. Here, we show that both crude and acidic polysaccharide extracts from Gastrodia rhizomes inhibited the total cholesterol and LDL levels. Moreover, there was a significantly suppressed atherosclerosis risk due to the acidic polysaccharide extract from Gastrodia rhizome. Taken together, our results suggested that acidic polysaccharide extracts from Gastrodia rhizomes might be beneficial for lowering the incidence of CVD and atherosclerosis by reducing the de novo synthesis of total cholesterol and the LDL levels. PMID:22408412

  12. Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice.

    PubMed

    Tavori, Hagai; Fan, Daping; Giunzioni, Ilaria; Zhu, Lin; Linton, MacRae F; Fogo, Agnes B; Fazio, Sergio

    2014-10-01

    Lipoprotein glomerulopathy (LPG) is a renal disease often accompanied by dyslipidemia and increased serum apoE levels. apoESendai (Arg145Pro), a rare mutant based on the apoE3 sequence carrying an apoE2 charge, causes LPG in humans and transgenic mice, but its effects on the artery wall are unknown. Macrophage expression of apoESendai may also directly influence renal and arterial homeostasis. We investigated the effects of macrophage-expressed apoESendai in apoE(-/-) mice with or without LDL receptor (LDLR). Murine bone marrow transduced to express apoE2, apoE3, or apoESendai was transplanted into lethally irradiated mice. Macrophage apoESendai expression reduced aortic lesion size and inflammation by 32 and 28%, respectively, compared with apoE2 in apoE(-/-) recipients. No differences in lesion size or inflammation were found between apoESendai and apoE3 in apoE(-/-) recipients. Macrophage apoESendai expression also reduced aortic lesion size by 18% and inflammation by 29% compared with apoE2 in apoE(-/-)/LDLR(-/-) recipients. Glomerular lesions compatible with LPG with increased mesangial matrix, extracellular lipid accumulation, and focal mesangiolysis were only observed in apoE(-/-)/LDLR(-/-) mice expressing apoESendai. Thus, macrophage expression of apoESendai protects against atherosclerosis while causing lipoprotein glomerulopathy. This is the first demonstration of an apoprotein variant having opposing effects on vascular and renal homeostasis. PMID:25183802

  13. 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

  14. Resveratrol, Wine, and Atherosclerosis

    PubMed Central

    Prasad, Kailash

    2012-01-01

    This review emphasizes the effects of resveratrol on factors involved in the mechanism of atherosclerosis and risk factors for atherosclerosis. The effects of wine and resveratrol on atherosclerosis are also discussed. Resveratrol is a potent antioxidant and an anti-inflammatory agent. It reduces the expression of cell adhesion molecules, monocyte colony stimulating factors, matrix metalloproteinases, and growth factors; and inhibits platelet aggregation and vascular smooth muscle cell proliferation. It reduces the serum levels of total cholesterol, triglycerides (TG), and raises high-density lipoprotein cholesterol, inhibits expression of C-reactive protein and lowers the levels of advanced glycation end products and its receptor in the vascular tissue. It lowers the risk factors for plaque rupture. Epidemiological data show that moderate consumption of alcohol has an inverse association with carotid atherosclerosis while high consumption has a positive association with carotid atherosclerosis. Wine reduces the extent of atherosclerosis in animal model. The antiatherosclerotic effect of wine is mainly due to it resveratrol content. Resveratrol reduces the extent of atherosclerosis in animal model of atherosclerosis (apolipoprotein [Apo] E-deficient and Apo E?/?/low-density lipoprotein receptor-deficient mice and macrophage). In rabbit model of atherosclerosis, both reduction and acceleration of atherosclerosis have been reported with resveratrol. There are no data for regression and slowing of progression of atherosclerosis. Robust clinical trials for suppression of atherosclerosis are lacking. In conclusion, resveratrol has potential but experimental studies in depth and robust clinical trials are lacking for this agent to be of any value in the primary and secondary prevention of coronary and peripheral artery disease. PMID:23450206

  15. Irbesartan, an FDA approved drug for hypertension and diabetic nephropathy, is a potent inhibitor for hepatitis B virus entry by disturbing Na(+)-dependent taurocholate cotransporting polypeptide activity.

    PubMed

    Wang, Xue-Jun; Hu, Wei; Zhang, Ting-Yu; Mao, Ying-Ying; Liu, Nan-Nan; Wang, Sheng-Qi

    2015-08-01

    The liver-specific Na(+)-dependent taurocholate cotransporting polypeptide (NTCP) was recently identified as an entry receptor for hepatitis B virus (HBV) hepatotropic infection. In this study, an NTCP-overexpressing HepG2 cell line named HepG2.N9 susceptible to HBV infection was established using transcription activator-like effector nucleases (TALEN) technology. Using this cell line, irbesartan, the new NTCP-interfering molecule reported recently, was demonstrated here to effectively inhibit HBV infection with an IC50 of 3.3?M for hepatitis B e antigen (HBeAg) expression and exhibited no obvious cytotoxicity up to 1000?M. Irbesartan suppressed HBV uptake weakly but inhibited HBV covalently closed circular DNA (cccDNA) formation efficiently at physiological temperature. These results suggested that irbesartan targeted HBV infection at a post-uptake prior to cccDNA formation step such as the cell membrane fusion. Based on these findings, irbesartan, an FDA approved drug for hypertension and diabetic nephropathy, could be a potential candidate for treatment of HBV infection although further in vivo experiments are required. PMID:26086883

  16. Probucol Protects Against Atherosclerosis Through Lipid-lowering and Suppressing Immune Maturation of CD11c+ Dendritic Cells in STZ-induced Diabetic LDLR-/- Mice.

    PubMed

    Zhu, Hong; Jin, Xueting; Zhao, Jingjing; Dong, Zhen; Ma, Xin; Xu, Fang; Huang, Wei; Liu, George; Zou, Yunzeng; Wang, Keqiang; Hu, Kai; Sun, Aijun; Ge, Junbo

    2015-06-01

    Probucol, an agent characterized by lipid-lowering and antioxidant property, retards atherosclerosis effectively. To test the hypothesis that probucol might act its antiatherosclerotic role by suppressing immune maturation of dendritic cells (DCs), 7-week-old LDLR mice were rendered diabetic with streptozotocin (STZ) and then fed either a high-fat diet only or added with 0.5% (wt/wt) probucol for 4 months, and human monocyte-derived dendritic cells were preincubated with or without probucol and stimulated by oxidized low-density lipoprotein. In STZ-induced diabetic LDLR mice, probucol treatment significantly lowered plasma total cholesterol and high-density lipoprotein-cholesterol levels; regressed aortic atherosclerotic lesions; reduced splenic CD40, CD80, CD86, MHC-II expression, and plasma IL-12p70 production; and decreased the expression of CD11c DCs within atherosclerotic lesions. In vitro, oxidized low-density lipoprotein promoted human monocyte-derived dendritic cells maturation; stimulated CD40, CD86, CD1a, HLA-DR expression; increased tumor necrosis factor-? production; and decreased IL-4 production. However, these effects were obviously inhibited by probucol pretreatment. In conclusion, our study indicated that probucol effectively retarded atherosclerosis at least partly through lipid-lowering and inhibiting immune maturation of CD11c DCs in STZ-induced diabetic LDLR mice. PMID:25714599

  17. Probucol Protects Against Atherosclerosis Through Lipid-lowering and Suppressing Immune Maturation of CD11c+ Dendritic Cells in STZ-induced Diabetic LDLR?/? Mice

    PubMed Central

    Zhu, Hong; Jin, Xueting; Zhao, Jingjing; Dong, Zhen; Ma, Xin; Xu, Fang; Huang, Wei; Liu, George; Zou, Yunzeng; Wang, Keqiang; Hu, Kai; Sun, Aijun

    2015-01-01

    Abstract: Probucol, an agent characterized by lipid-lowering and antioxidant property, retards atherosclerosis effectively. To test the hypothesis that probucol might act its antiatherosclerotic role by suppressing immune maturation of dendritic cells (DCs), 7-week-old LDLR?/? mice were rendered diabetic with streptozotocin (STZ) and then fed either a high-fat diet only or added with 0.5% (wt/wt) probucol for 4 months, and human monocyte-derived dendritic cells were preincubated with or without probucol and stimulated by oxidized low-density lipoprotein. In STZ-induced diabetic LDLR?/? mice, probucol treatment significantly lowered plasma total cholesterol and high-density lipoprotein-cholesterol levels; regressed aortic atherosclerotic lesions; reduced splenic CD40, CD80, CD86, MHC-II expression, and plasma IL-12p70 production; and decreased the expression of CD11c+ DCs within atherosclerotic lesions. In vitro, oxidized low-density lipoprotein promoted human monocyte–derived dendritic cells maturation; stimulated CD40, CD86, CD1a, HLA-DR expression; increased tumor necrosis factor-? production; and decreased IL-4 production. However, these effects were obviously inhibited by probucol pretreatment. In conclusion, our study indicated that probucol effectively retarded atherosclerosis at least partly through lipid-lowering and inhibiting immune maturation of CD11c+ DCs in STZ-induced diabetic LDLR?/? mice. PMID:25714599

  18. Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction

    Microsoft Academic Search

    Barry M. Massie; Peter E. Carson; John J. McMurray; Michel Komajda; Robert McKelvie; Michael R. Zile; Susan Anderson; Mark Donovan; Erik Iverson; Christoph Staiger; Agata Ptaszynska; Ralph H. Johnson; Veterans Affairs

    2010-01-01

    Background Approximately 50% of patients with heart failure have a left ventricular ejection fraction of at least 45%, but no therapies have been shown to improve the outcome of these patients. Therefore, we studied the effects of irbesartan in patients with this syndrome. Methods We enrolled 4128 patients who were at least 60 years of age and had New York

  19. Safety and tolerability of fixed-dose irbesartan/hydrochlorothiazide for rapid control of severe hypertension.

    PubMed

    Neutel, Joel M; Franklin, Stanley S; Bhaumik, Amitabha; Lapuerta, Pablo; Oparil, Suzanne

    2009-10-01

    This prospective, double-blind, multicenter trial compared the safety and tolerability of irbesartan/hydrochlorothiazide (HCTZ) fixed-dose combination therapy with irbesartan monotherapy in patients with severe hypertension (seated diastolic blood pressure (SeDBP) >or=110 mm Hg, mean BP 172/113 mm Hg at baseline). Patients were randomized 2:1 to 7 weeks' irbesartan/HCTZ 150/12.5 mg to 300/25 mg (n = 468) or irbesartan 150 mg to 300 mg (n = 227). The incidence of treatment-related adverse events (AEs) was similar with combination and monotherapy (11.3% and 10.1%), and most AEs were mild-to-moderate. The combined incidence of prespecified AEs was lower with irbesartan/HCTZ than with irbesartan (8.8% vs. 11.5%). There were no treatment-related serious AEs or deaths. At week 5, more patients achieved SeDBP < 90 mm Hg compared to irbesartan (47% vs. 33%; P = 0.0005). Despite more rapid and aggressive BP lowering, initial fixed-dose irbesartan/HCTZ demonstrated a comparable AE profile to irbesartan monotherapy in patients with severe hypertension. PMID:19886855

  20. The effects of age and gender on the pharmacokinetics of irbesartan

    PubMed Central

    Vachharajani, Nimish N; Shyu, Wen Chyi; Smith, Robert A; Greene, Douglas S

    1998-01-01

    Aims Single dose pharmacokinetics and safety of irbesartan, an angiotensin II receptor antagonist, were evaluated in healthy young and elderly male and female subjects. Methods Irbesartan was administered as two 25 mg capsules after a 10 h fast to 12 young men, 12 young women, 12 elderly men and 12 elderly women. Serial blood and urine sample were collected up to 96 h after the dose. Plasma and urine samples were analysed for irbesartan by h.p.l.c./fluorescence methods. Results No statistically significant gender effects were observed in peak plasma concentration (Cmax), area under the curve (AUC), and terminal elimination half-life (t1/2) of irbesartan. The geometric mean AUC and Cmax increased by about 43% and 49%, respectively, in the elderly subjects. Also the time to peak was significantly shorter in the elderly subjects compared with that observed in the young subjects. Renal clearance of irbesartan was significantly reduced in the elderly females but this reduction is not likely to be of any clinical relevance since less than 3% of the administered dose of irbesartan is excreted unchanged in the urine. Conclusions Although there was an effect of age on the pharmacokinetics of irbesartan, based on the safety and efficacy profile, no adjustment in irbesartan dosage is necessary with respect to age or gender. PMID:9862252

  1. A comparison of the efficacy and safety of irbesartan/HCTZ combination therapy with irbesartan and HCTZ monotherapy in the treatment of moderate hypertension.

    PubMed

    Neutel, J M; Franklin, S S; Lapuerta, P; Bhaumik, A; Ptaszynska, A

    2008-04-01

    This prospective, double-blind, parallel-group study randomized patients with moderate hypertension (seated systolic blood pressure (SeSBP) 160-179 mm Hg when seated diastolic blood pressure (SeDBP) <110 mm Hg; or SeDBP 100-109 mm Hg when SeSBP <180 mm Hg) 3:1:1 to treatment with irbesartan 300 mg/hydrochlorothiazide (HCTZ) 25 mg combination therapy (n=328), irbesartan 300 mg monotherapy (n=106) or HCTZ monotherapy 25 mg (n=104). Treatment was initiated at half dose, with forced titration to full dose after two weeks followed by ten further weeks' treatment. The primary efficacy variable was the mean reduction in SeSBP from baseline to week 8. Baseline characteristics were similar between groups, with mean baseline blood pressure approximately 162/98 mm Hg; the mean age was 55 years. At week 8 there was a reduction in SeSBP of 27.1 mm Hg with irbesartan/HCTZ, compared with 22.1 mm Hg with irbesartan monotherapy (P=0.0016) and 15.7 mm Hg with HCTZ (P<0.0001). Both the rate of decline and the total degree of decline achieved were greatest with irbesartan/HCTZ and least with HCTZ. A significantly greater percentage of patients reached a treatment goal of SeSBP <140 mm Hg and SeDBP <90 mm Hg by week 8 with irbesartan/HCTZ (53.4%), compared with irbesartan (40.6%; P=0.0254) and HCTZ (20.2%; P<0.0001) alone. Treatment was well tolerated in all three-treatment groups with a slight increase in adverse events in the combination therapy group. In conclusion, irbesartan/HCTZ (300/25 mg) is well tolerated and achieves rapid and sustained reductions in both systolic blood pressure and diastolic blood pressure in patients with moderate hypertension. PMID:17928878

  2. Long-term use and tolerability of irbesartan for control of hypertension

    PubMed Central

    Forni, Valentina; Wuerzner, Grégoire; Pruijm, Menno; Burnier, Michel

    2011-01-01

    In this review, we discuss the pharmacological and clinical properties of irbesartan, a noncompetitive angiotensin II receptor type 1 antagonist, successfully used for more than a decade in the treatment of essential hypertension. Irbesartan exerts its antihypertensive effect through an inhibitory effect on the pressure response to angiotensin II. Irbesartan 150–300 mg once daily confers a lasting effect over 24 hours, and its antihypertensive efficacy is further enhanced by the coadministration of hydrochlorothiazide. Additionally and partially beyond its blood pressure-lowering effect, irbesartan reduces left ventricular hypertrophy, favors right atrial remodeling in atrial fibrillation, and increases the likelihood of maintenance of sinus rhythm after cardioversion in atrial fibrillation. In addition, the renoprotective effects of irbesartan are well documented in the early and later stages of renal disease in type 2 diabetics. Furthermore, both the therapeutic effectiveness and the placebo-like side effect profile contribute to a high adherence rate to the drug. Currently, irbesartan in monotherapy or combination therapy with hydrochlorothiazide represent a rationale pharmacologic approach for arterial hypertension and early-stage and late-stage diabetic nephropathy in hypertensive type II diabetics. PMID:21949635

  3. Effect of ?-cyclodextrin on solubilization and complexation of irbesartan: influence of pH and excipients.

    PubMed

    Muankaew, Chutimon; Jansook, Phatsawee; Stefánsson, Einar; Loftsson, Thorsteinn

    2014-10-20

    In effort to prepare an eye drop formulation of irbesartan, the effect of ?-cyclodextrin complexation on irbesartan solubilization in aqueous solutions was investigated. The optimum cyclodextrin concentration for formation of irbesartan/cyclodextrin inclusion complex was found to be 10% (w/v) and the solubility of ionized irbesartan/?-cyclodextrin complex (at pH 7.2) was shown to be three fold greater than that of the unionized complex (at pH 4.3). The irbesartan flux through semipermeable membranes increased with increasing ?-cyclodextrin concentration at both pH values. However, the ionized complex displayed decrease in the drug permeation coefficient with increasing cyclodextrin concentration. The effect of four pharmaceutical excipients on the cyclodextrin solubilization was investigated. EDTA, hydroxypropyl methylcellulose, and tyloxapol increased complexation efficiency of ?-cyclodextrin while benzalkonium chloride had negligible effect. The largest solubilization was observed in the eye drop vehicle that contained all four excipients in addition to ?-cyclodextrin. Dynamic light scattering measurements disclosed that excipients had impact on size of complex aggregates and consequently on the drug flux through the semipermeable membranes. Complex of irbesartan/?-cyclodextrin was characterized by FT-IR, (1)H NMR, XRPD, and TEM techniques. PMID:25128698

  4. A comparison of the efficacy and safety of irbesartan/hydrochlorothiazide combination therapy with irbesartan monotherapy in the treatment of moderate or severe hypertension in diabetic and obese hypertensive patients: a post-hoc analysis review.

    PubMed

    Neutel, Joel M

    2011-07-01

    Hypertension is difficult to treat in patients with type 2 diabetes mellitus (T2DM) or obesity. Combination therapies are often required to effectively lower blood pressure (BP) and attain BP goals. In this post-hoc analysis of 2 prospective, randomized, controlled studies in patients with uncontrolled or untreated moderate or severe hypertension, the efficacy and safety of treatment with irbesartan/hydrochlorothiazide (HCTZ) and irbesartan was assessed in 2 separate analyses: patients with diabetes (n=143) and by obesity status (n=1125). Patients received irbesartan/HCTZ (150 mg/12.5 mg titrated to 300 mg/25 mg) or irbesartan (150 mg titrated to 300 mg) for 7 (severe hypertension study) or 12 (moderate hypertension study) weeks. Efficacy comparisons between treatment groups were performed using Fisher's exact tests. After 7 to 8 weeks of treatment, systolic BP (SBP)/diastolic BP (DBP) decreased in patients with diabetes by 26.9/17.8 mm Hg and 21.8/15.8 mm Hg after irbesartan/HCTZ and irbesartan treatment, respectively (P [SBP]=0.09, P [DBP]=0.27). In obese patients (n=544), SBP/DBP decreased by 29.4/20.2 mm Hg and 20.1/15.9 mm Hg after irbesartan/HCTZ and irbesartan treatment, respectively (P<0.0001). More patients with T2DM reached the BP goal of <130/80 mm Hg at week 7 to 8 in the irbesartan/HCTZ group than in the irbesartan group (12% vs 5%), although not statistically significant (P=0.22). Significantly more obese patients reached their respective BP goals in the irbesartan/HCTZ group than in the irbesartan group (48% vs 23%; P<0.0001). Treatment-emergent adverse event rates were similar between treatment groups regardless of the presence of diabetes or body mass index (BMI) status. In patients with moderate or severe hypertension and with a BMI ? 30 kg/m(2), initial treatment with irbesartan/HCTZ combination therapy was more effective than irbesartan monotherapy. PMID:21680997

  5. CYP2C9*3 and *13 alleles significantly affect the pharmacokinetics of irbesartan in healthy Korean subjects

    Microsoft Academic Search

    Chang-Ik Choi; Mi-Jeong Kim; Eun-Kyung Chung; Hye-In Lee; Choon-Gon Jang; Jung-Woo Bae; Seok-Yong Lee

    Purpose  To evaluate the effects of two major polymorphisms of CYP2C9, CYP2C9*3 and CYP2C9*13, on the pharmacokinetics of irbesartan in healthy Korean volunteers.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A single 150-mg oral dose of irbesartan was given to 28 Korean volunteers, who had different CYP2C9 genotypes (12, 10, and 6 carriers of CYP2C9*1\\/*1, *1\\/*3, and *1\\/*13 genotypes respectively). Irbesartan levels were analyzed using HPLC fluorescence in

  6. A validated stability indicating HPTLC method for simultaneous estimation of irbesartan and hydrochlorothiazide

    PubMed Central

    Khodke, Amol S; Potale, Laxman V; Damle, Mrinalini C; Bothara, Kailash G

    2010-01-01

    Introduction: Irbesartan, a diazaspiro angiotensin II blocker, is marketed in combination with Hydrochlorothiazide, which is a diuretic acting on distal convoluted tubule; for synergistic anti-hypertensive action. The present study deals with development and validation of a stability indicating HPTLC method for simultaneous estimation of Irbesartan and Hydrochlorothiazide using TLC plates precoated with Silica gel 60F254 and the mobile phase comprising Acetonitrile: Chloroform in the ratio of 5:6 v/v. Irbesartan and Hydrochlorothiazide were well resolved with Rf 0.27 ± 0.03 and 0.45 ± 0.03, respectively. Wavelength selected for the quantization was 270 nm. Inherent stability of these drugs was studied by exposing both drugs to various stress conditions as per ICH guidelines viz. Dry heat, oxidative, photolysis (UV and cool white fluorescent light) and hydrolytic conditions under different pH values. Results: Both the drugs were not degraded under dry heat and photolytic conditions, but showed degradation under hydrolytic condition. The degraded products of Irbesartan and hydrochlorothiazide were well resolved from the individual bulk drug response. Conclusion: The developed method is found to be simple, specific, precise and stability indicating. The specificity of the method was confirmed by peak purity profile of the resolved peaks. PMID:23781414

  7. What Causes Atherosclerosis?

    MedlinePLUS

    ... insulin resistance or diabetes Plaque may begin to build up where the arteries are damaged. Over time, plaque ... is atherosclerosis? 05/22/2014 Describes how the build-up of plaque over time causes atherosclerosis which can ...

  8. Efficacy and safety of irbesartan/HCTZ combination therapy as initial treatment for rapid control of severe hypertension.

    PubMed

    Neutel, Joel M; Franklin, Stanley S; Oparil, Suzanne; Bhaumik, Amitabha; Ptaszynska, Agata; Lapuerta, Pablo

    2006-12-01

    Severe hypertension is difficult to control. This prospective, randomized, double-blind, active-controlled, multicenter trial compared efficacy and safety of once-daily irbesartan/hydrochlorothiazide (HCTZ) combination therapy with irbesartan monotherapy in severe hypertension. Patients who were untreated or uncontrolled on monotherapy (seated diastolic blood pressure [BP] > or =110 mm Hg) received fixed-dose irbesartan 150 mg/HCTZ 12.5 mg combination therapy for 7 weeks, force-titrated to irbesartan 300 mg/HCTZ 25 mg at week 1 (n=468); or irbesartan 150 mg monotherapy, force-titrated to 300 mg at week 1 (n=269). Significantly more patients on combination therapy achieved seated diastolic BP <90 mm Hg at week 5 (primary end point) compared with monotherapy recipients (47.2% vs 33.2%; P=.0005). Likewise, significantly more patients attained goals per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) (<140/90 mm Hg) at week 5 (34.6% vs 19.2%, respectively; P<.0001), while the mean difference between combination and monotherapy in seated diastolic BP and seated systolic BP was 4.7 mm Hg and 9.7 mm Hg (P<.0001). Greater and more rapid BP reduction with irbesartan/HCTZ was achieved without additional side effects. PMID:17170610

  9. 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

  10. Efficacy and Safety of Fixed Combinations of Irbesartan/Hydrochlorothiazide in Hypertensive Women: The Inclusive Trial

    PubMed Central

    Cable, Greg; Neutel, Joel M.; Saunders, Elijah

    2008-01-01

    Abstract Objective This post hoc analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) in a diverse population of hypertensive women. Methods INCLUSIVE was a multicenter, prospective, open-label, single-arm trial. Adult subjects had uncontrolled systolic blood pressure (SBP 140–159 mm Hg; 130–159 mm Hg for those with type 2 diabetes mellitus [T2DM]) after ?4 weeks of antihypertensive monotherapy. Treatment was sequential: placebo (4–5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and irbesartan/HCTZ 300/25 mg (8 weeks). Mean changes from baseline to treatment end in SBP and diastolic blood pressure (DBP), BP goal attainment, and safety were assessed. Results Treatment with irbesartan/HCTZ was associated with significant mean reductions in BP (intent-to-treat population, n?=?370; SBP/DBP: ?22.9/?10.3 ± 14.7/8.8 mm Hg). Improvements in SBP were observed in all subgroups (p?Irbesartan/HCTZ treatment was effective and well tolerated in a diverse population of women whose BP was previously uncontrolled on monotherapy. PMID:18681815

  11. Irbesartan/hydrochlorothiazide for the treatment of isolated systolic hypertension: a subgroup analysis of the INCLUSIVE trial.

    PubMed

    Chrysant, Steven G; Neutel, Joel M; Ferdinand, Keith C

    2009-04-01

    This post hoc analysis of the Irbesartan/Hydrochlorothiazide (HCTZ) Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of fixed-dose irbesartan/HCTZ in patients with isolated systolic hypertension. Adults with uncontrolled systolic blood pressure (SBP) (140-179 mm Hg; 130-179 mm Hg in type 2 diabetes) after 4 weeks or more of antihypertensive monotherapy once-daily treatment with placebo for 4-5 weeks, followed by HCTZ 12.5 mg for 2 weeks, irbesartan/HCTZ 150/12.5 mg for 8 weeks, and then irbesartan/HCTZ 300/25 mg for 8 weeks, in a prospective, multicenter, open-label, single-arm study. In patients with isolated systolic hypertension (n = 443) and the total study population (n = 736), irbesartan/HCTZ treatment for 16 weeks provided comparable mean blood pressure (BP) reductions from baseline (21.4/10.1 mm Hg vs 21.5/10.4 mm Hg; p < .001 vs baseline) and high SBP control rates (74% vs 77%). Patients with isolated systolic hypertension and concomitant type 2 diabetes experienced smaller BP reductions (17.9/8.7 mm Hg vs 22.9/10.7 mm Hg) and lower rates of SBP control (< 130 mm Hg, 47%) than those without diabetes (< 140 mm Hg, 87%). BP reductions from baseline and SBP control rates were similar across isolated systolic hypertension subgroups (> or = 65 vs < 65 years, sex, race, and metabolic syndrome status). Irbesartan/HCTZ was well tolerated, with drug-related adverse events (dizziness, < or = 3%; upper respiratory tract infection, < or = 2%) occurring with similar rates in the isolated systolic hypertension and total population. Fixed-dose irbesartan/HCTZ combination treatment provided effective and well-tolerated BP lowering in a diverse population of patients with isolated systolic hypertension. PMID:19397219

  12. Genetic Variation and Atherosclerosis

    PubMed Central

    Biros, Erik; Karan, Mirko; Golledge, Jonathan

    2008-01-01

    A family history of atherosclerosis is independently associated with an increased incidence of cardiovascular events. The genetic factors underlying the importance of inheritance in atherosclerosis are starting to be understood. Genetic variation, such as mutations or common polymorphisms has been shown to be involved in modulation of a range of risk factors, such as plasma lipoprotein levels, inflammation and vascular calcification. This review presents examples of present studies of the role of genetic polymorphism in atherosclerosis. PMID:19424482

  13. Efficacy and safety of fixed combinations of irbesartan/hydrochlorothiazide in older vs younger patients with hypertension uncontrolled with monotherapy.

    PubMed

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

    2008-01-01

    Subgroup analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) fixed combinations in patients aged 65 years or older with uncontrolled systolic blood pressure (SBP) after >or= 4 weeks of antihypertensive monotherapy. The INCLUSIVE trial was a prospective, open-label, single-arm trial carried out in 119 sites. Of 844 patients completing placebo treatment, 212 were aged 65 years or older. Participants received treatment with placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and then irbesartan/HCTZ 300/25 mg (8 weeks). From baseline to week 18 (n=184, intent-to-treat population), mean change in SBP was -23.0+/-13.3 mm Hg (P<.001) and diastolic BP (DBP) was -10.9+/-7.7 mm Hg (P<.001). Mean SBP/DBP at study end was 134.0+/-14.7/75.1+/-8.4 mm Hg, and SBP, DBP, and SBP/DBP goal was achieved in 73%, 96%, and 72% of patients, respectively. Irbesartan/HCTZ combination therapy allowed SBP goal attainment in 73% of patients aged 65 years or older whose hypertension was previously uncontrolled with antihypertensive monotherapy. PMID:18174757

  14. 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.

  15. Vaccination to modulate atherosclerosis.

    PubMed

    Kimura, Takayuki; Tse, Kevin; Sette, Alessandro; Ley, Klaus

    2015-05-01

    Atherosclerosis is a chronic inflammatory disease of the artery wall. Adaptive immunity plays a key role in the pathogenesis of atherosclerosis. Recently, modulation of the immune response against atherosclerotic plaque antigen(s) has attracted attention as a potentially preventive and therapeutic approach. Here, we review a series of studies on immunization with various antigens targeting treatment and prevention of atherosclerosis. Atherosclerosis-related antigens include oxidized low-density lipoprotein (LDL), apolipoprotein B-100 (ApoB-100) and heat shock protein (HSP) 60/65. Accumulating evidence supports the idea that immunization with these antigenic proteins or peptides may reduce atherosclerosis. In this review, we discuss the current status of immunization studies and possible associated mechanisms of atheroprotection. PMID:25683179

  16. Vinpocetine attenuates lipid accumulation and atherosclerosis formation.

    PubMed

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

    2013-05-10

    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. PMID:23583194

  17. Vinpocetine Attenuates Lipid Accumulation and Atherosclerosis Formation

    PubMed Central

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

    2013-01-01

    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 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 PMID:23583194

  18. T cells in atherosclerosis

    PubMed Central

    2013-01-01

    Atherosclerosis is a chronic inflammatory disease of the artery wall. Atherosclerotic lesions contain monocytes, macrophages, smooth muscle cells and T lymphocytes. Here, we review the role of T-lymphocyte subsets in atherosclerosis. Among CD4+ T cells, Th1 cells are pro-atherogenic, Treg cells are athero-protective and the role of Th2 and Th17 cells remains unclear. The role of follicular helper T cells in atherosclerosis remains unknown, as is the role of CD8+ T cells. NKT cells bind glycolipid antigens and exert a pro-atherogenic role. The antigen specificity of T-cell responses in atherosclerosis is poorly understood. In order to enable antigen-specific prevention or therapy, a better understanding of these mechanisms is needed. PMID:24154816

  19. Chitinase Inhibition Promotes Atherosclerosis in Hyperlipidemic Mice

    PubMed Central

    Kitamoto, Shiro; Egashira, Kensuke; Ichiki, Toshihiro; Han, Xinbing; McCurdy, Sara; Sakuda, Shohei; Sunagawa, Kenji; Boisvert, William A.

    2014-01-01

    Chitinase 1 (CHIT1) is secreted by activated macrophages. Chitinase activity is raised in atherosclerotic patient sera and is present in atherosclerotic plaque. However, the role of CHIT1 in atherosclerosis is unknown. Preliminary studies of atherosclerosis in cynomolgous monkeys revealed CHIT1 to be closely correlated with areas of macrophage infiltration. Thus, we investigated the effects of a chitinase inhibitor, allosamidin, on macrophage function in vitro and on atherosclerotic development in vivo. In RAW264.7 cells, allosamidin elevated monocyte chemoattractant protein 1 and tumor necrosis factor alpha expression, and increased activator protein 1 and nuclear factor-?B transcriptional activity. Although inducible nitric oxide synthase, IL-6, and IL-1? expression were increased, Arg1 expression was decreased by chitinase inhibition, suggesting that suppression of CHIT1 activity polarizes macrophages into a M1 phenotype. Allosamidin decreased scavenger receptor AI, CD36, ABCA1, and ABCG1 expression which led to suppression of cholesterol uptake and apolipoprotein AI-mediated cholesterol efflux in macrophages. These effects were confirmed with CHIT1 siRNA transfection and CHIT1 plasmid transfection experiments in primary macrophages. Apolipoprotein E-deficient hyperlipidemic mice treated for 6 weeks with constant administration of allosamidin and fed an atherogenic diet showed aggravated atherosclerotic lesion formation. These data suggest that CHIT1 exerts protective effects against atherosclerosis by suppressing inflammatory responses and polarizing macrophages toward an M2 phenotype, and promoting lipid uptake and cholesterol efflux in macrophages. PMID:23685110

  20. Efficacy and safety of irbesartan/HCTZ in severe hypertension according to cardiometabolic factors.

    PubMed

    Franklin, Stanley S; Neutel, Joel M

    2010-07-01

    This post hoc analysis of a 7-week, randomized, double-blind trial evaluated the efficacy and safety of initial irbesartan/hydrochlorothiazide treatment in 468 patients with severe, uncontrolled, hypertension (diastolic blood pressure [DBP] > or =100 mm Hg) at high cardiovascular risk. Systolic blood pressure (SBP)/DBP reductions ranged from 28.0 to 42.9/22.9 to 27.2 mm Hg in patients with obesity, diabetes, baseline SBP > or =180 mm Hg, and in the elderly. Blood pressure control to <140/90 mm Hg in the age and obesity subgroups ranged from 32.1% to 39.2% while control to <130/80 mm Hg in patients with diabetes was 11.5%. After 1 week of therapy, 72.5% of patients no longer had SBP > or =180 mm Hg; by 7 weeks, 51.3% had SBP 140 to 159 mm Hg and 26.5% had SBP <140 mm Hg. Treatment was well tolerated regardless of the subgroup. No excess of prespecified events was noted. Thus, initial treatment with irbesartan/hydrochlorothiazide was rapidly effective in high-risk, difficult-to-treat, severely hypertensive patients. PMID:20629810

  1. Antihypertensive efficacy of Irbesartan/HCTZ in men and women with the metabolic syndrome and type 2 diabetes.

    PubMed

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

    2006-07-01

    This subgroup analysis of the Irbesartan/Hydrochlorothiazide (HCTZ) Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/HCTZ fixed combinations in adults with uncontrolled systolic blood pressure (SBP) (140-159 mm Hg; 130-159 mm Hg for type 2 diabetes mellitus [T2DM]) after >or=4 weeks of antihypertensive monotherapy. Treatment was sequential: placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and irbesartan/HCTZ 300/25 mg (8 weeks). In the intent-to-treat analysis, mean change from baseline (end of placebo phase) off all previous therapy to Week 18 (study end) in T2DM patients (n=227) was -18.2+/-14.1 mm Hg for SBP (primary end point; p<0.001) and -8.7+/-8.2 mm Hg for diastolic blood pressure (p<0.001). Mean SBP/diastolic blood pressure changes in patients with the metabolic syndrome (n=345) were -21.0+/-14.3/-10.4+/-8.5 mm Hg (p<0.001). Overall, 56% (95% confidence interval, 49%-62%) of T2DM and 73% (95% confidence interval, 68%-77%) of metabolic syndrome patients achieved SBP goal (<140 mm Hg; <130 mm Hg for T2DM). Goal attainment rates were significantly higher among women with the metabolic syndrome than men. Treatments appeared to be well tolerated. Irbesartan/HCTZ fixed combinations achieved SBP goals in over half of the T2DM patients and nearly three quarters of patients with the metabolic syndrome, with SBP uncontrolled on antihypertensive monotherapy. PMID:16849900

  2. Irbesartan Ameliorates Diabetic Nephropathy by Reducing the Expression of Connective Tissue Growth Factor and Alpha-Smooth-Muscle Actin in the Tubulointerstitium of Diabetic Rats

    Microsoft Academic Search

    Xiaojun Ren; Guangju Guan; Gang Liu; Gaohong Liu

    2009-01-01

    The effect of irbesartan on the expression of connective tissue growth factor (CTGF) and ?-smooth-muscle actin (?-SMA) in the renal tubulointerstitium of diabetic rats was investigated in our study. Diabetes was induced in male Wistar rats by intraperitoneal administration of streptozotocin (STZ), 60 mg·kg–1 body weight. The rats were then randomized to a diabetic group (DM) and an irbesartan therapy

  3. Inflammation in atherosclerosis

    Microsoft Academic Search

    Peter Libby

    2002-01-01

    Abundant data link hypercholesterolaemia to atherogenesis. However, only recently have we appreciated that inflammatory mechanisms couple dyslipidaemia to atheroma formation. Leukocyte recruitment and expression of pro-inflammatory cytokines characterize early atherogenesis, and malfunction of inflammatory mediators mutes atheroma formation in mice. Moreover, inflammatory pathways promote thrombosis, a late and dreaded complication of atherosclerosis responsible for myocardial infarctions and most strokes. The

  4. Macrophage Apoptosis in Advanced Atherosclerosis

    PubMed Central

    Tabas, Ira; Seimon, Tracie; Timmins, Jenelle; Li, Gang; Lim, Wahseng

    2009-01-01

    Plaque necrosis in advanced atheromata, which triggers acute atherothrombotic vascular events, is caused by the apoptosis of lesional macrophages coupled with defective phagocytic clearance of the dead cells. The central enabling event in macrophage apoptosis relevant to advanced atherosclerosis is the unfolded protein response (UPR), an endoplasmic reticulum (ER) stress pathway. The UPR effector CHOP (GADD153) amplifies release of ER Ca2+ stores, which activates a central integrator of apoptosis signaling, calcium/calmodulin-dependent protein kinase II (CaMKII). CaMKII, in turn, leads to activation of pro-apoptotic STAT1, induction of the death receptor Fas, and stimulation of the mitochondria-cytochrome c pathway of apoptosis. While these pathways are necessary for apoptosis, apoptosis occurs only when the cells are also exposed to one or more additional “hits.” These hits amplify pro-apoptotic pathways and/or suppress compensatory cell-survival pathways. A second hit relevant to atherosclerosis is activation of pattern recognition receptors (PRRs), such as scavenger and toll-like receptors. In vivo relevance is suggested by the fact that advanced human lesions express markers of UPR activation that correlate closely with the degree of plaque vulnerability and macrophage apoptosis. Moreover, studies with genetically altered mice have shown that ER stress and PRR activation are causative for advanced lesional macrophage apoptosis and plaque necrosis. In summary, a key cellular event in the conversion of benign to vulnerable atherosclerotic plaques is ER stress-induced macrophage apoptosis. Further understanding of the mechanisms and consequences of this event may lead to novel therapies directed at preventing the clinical progression of atheromata. PMID:19751413

  5. Macrophage death and defective inflammation resolution in atherosclerosis

    Microsoft Academic Search

    Ira Tabas

    2009-01-01

    A key event in atherosclerosis is a maladaptive inflammatory response to subendothelial lipoproteins. A crucial aspect of this response is a failure to resolve inflammation, which normally involves the suppression of inflammatory cell influx, effective clearance of apoptotic cells and promotion of inflammatory cell egress. Defects in these processes promote the progression of atherosclerotic lesions into dangerous plaques, which can

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

    PubMed

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

    2006-04-01

    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

  7. 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

  8. Insulin Resistance and Atherosclerosis

    PubMed Central

    Razani, Babak; Chakravarthy, Manu V.; Semenkovich, Clay F.

    2008-01-01

    Synopsis Insulin resistance characterizes type 2 diabetes and the metabolic syndrome, disorders associated with an increased risk of death due to macrovascular disease. In the past few decades, research from both the basic science and clinical arenas has enabled evidenced-based use of therapeutic modalities such as statins and angiotensin converting enzyme inhibitors to reduce cardiovascular (CV) mortality in insulin resistant patients. Recently, promising drugs such as the thiazolidinediones have come under scrutiny for possible deleterious CV effects. Ongoing research has broadened our understanding of the pathophysiology of atherosclerosis, implicating detrimental effects of inflammation and the cellular stress response on the vasculature. In this review, we address current thinking that is shaping our molecular understanding of insulin resistance and atherosclerosis. PMID:18775354

  9. Insulin resistance and atherosclerosis.

    PubMed

    Razani, Babak; Chakravarthy, Manu V; Semenkovich, Clay F

    2008-09-01

    Insulin resistance characterizes type 2 diabetes and the metabolic syndrome, disorders associated with an increased risk of death due to macrovascular disease. In the past few decades, research from both the basic science and clinical arenas has enabled evidence-based use of therapeutic modalities such as statins and angiotensin-converting enzyme inhibitors to reduce cardiovascular (CV) mortality in insulin-resistant patients. Recently, promising drugs such as the thiazolidinediones have come under scrutiny for possible deleterious CV effects. Ongoing research has broadened our understanding of the pathophysiology of atherosclerosis, implicating detrimental effects of inflammation and the cellular stress response on the vasculature. In this review, we address current thinking that is shaping our molecular understanding of insulin resistance and atherosclerosis. PMID:18775354

  10. Gene therapy for atherosclerosis

    Microsoft Academic Search

    D. J. Rader

    1997-01-01

    Although considerable progress has been made in the prevention and treatment of atherosclerotic cardiovascular disease, new\\u000a therapeutic strategies are still needed. Atherosclerosis is a systemic disease and represents an attractive target for the\\u000a development of somatic gene transfer intended to modulate systemic factors with the goal of inhibiting disease progression.\\u000a This approach should be differentiated from localized vascular gene delivery

  11. Inflammation and atherosclerosis

    Microsoft Academic Search

    Mehdi H. Shishehbor; Deepak L. Bhatt

    2004-01-01

    Inflammation plays a pivotal role in all stages of atherogenesis, from foam cell to plaque formation to rupture and ultimately\\u000a to thrombosis. Insight gained from recent basic and clinical data linking inflammation to atherosclerosis has yielded important\\u000a diagnostic and prognostic information. Low-grade chronic inflammation as measured by high sensitivity C-reactive protein predicts\\u000a future risk of acute coronary syndrome independent of

  12. Vascular Endothelium and Atherosclerosis

    Microsoft Academic Search

    P. Libby; M. Aikawa; M. K. Jain

    Atherosclerosis depends critically on altered behavior of the intrinsic cells of the artery wall, the endothelial cells and\\u000a smooth muscle cells, and inflammatory leukocytes that join them in the arterial intima during the atherogenic process. The\\u000a homeostatic properties of the normal endothelium contribute importantly to maintenance of aspects of arterial health including\\u000a the appropriate regulation of blood flow, a basal

  13. Macrophage death and defective inflammation resolution in atherosclerosis

    PubMed Central

    Tabas, Ira

    2010-01-01

    A key event in atherosclerosis is a maladaptive inflammatory response to subendothelial lipoproteins. A critical aspect of this response is failure of inflammation resolution, which normally consists of suppression of inflammatory cell influx, effective clearance of apoptotic cells (efferocytosis), and promotion of inflammatory cell egress. Defects in these processes promote the progression of atherosclerotic lesions into dangerous plaques, which can trigger atherothrombotic vascular disease, the leading cause of death in industrialized societies. This review will provide an overview of these concepts, with a focus on macrophage death, defective efferocytosis, and novel therapeutic strategies designed to boost inflammation resolution in atherosclerosis. PMID:19960040

  14. Endothelial progenitor cells in atherosclerosis

    PubMed Central

    Du, Fuyong; Zhou, Jun; Gong, Ren; Huang, Xiao; Pansuria, Meghana; Virtue, Anthony; Li, Xinyuan; Wang, Hong; Yang, Xiao-Feng

    2012-01-01

    Endothelial progenitor cells (EPCs) are involved in the maintenance of endothelial homoeostasis and in the process of new vessel formation. Experimental and clinical studies have shown that atherosclerosis is associated with reduced numbers and dysfunction of EPCs; and that medications alone are able to partially reverse the impairment of EPCs in patients with atherosclerosis. Therefore, novel EPC-based therapies may provide enhancement in restoring EPCs’ population and improvement of vascular function. Here, for a better understanding of the molecular mechanisms underlying EPC impairment in atherosclerosis, we provide a comprehensive overview on EPC characteristics, phenotypes, and the signaling pathways underlying EPC impairment in atherosclerosis. PMID:22652782

  15. 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

  16. Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan.

    PubMed

    Patel, Jaydeep; Patel, Anjali; Raval, Mihir; Sheth, Navin

    2011-01-01

    Irbesartan (IRB) is an angiotensin II receptor blocker antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of poorly water-soluble IRB. The solubility of IRB in various oils was determined to identify the oil phase of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. The optimized SNEDDS formulation contained IRB (75 mg), Cremophor(®) EL (43.33%), Carbitol(®) (21.67%) and Capryol(®) 90 (32%). SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size and zeta potential. The optimized formulation of IRB-loaded SNEDDS exhibited complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug solution by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of IRB from SNEDDS compared with the pure drug solution. These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability of poorly water-soluble IRB. PMID:22171286

  17. Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan

    PubMed Central

    Patel, Jaydeep; Patel, Anjali; Raval, Mihir; Sheth, Navin

    2011-01-01

    Irbesartan (IRB) is an angiotensin II receptor blocker antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of poorly water-soluble IRB. The solubility of IRB in various oils was determined to identify the oil phase of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. The optimized SNEDDS formulation contained IRB (75 mg), Cremophor® EL (43.33%), Carbitol® (21.67%) and Capryol® 90 (32%). SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size and zeta potential. The optimized formulation of IRB-loaded SNEDDS exhibited complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug solution by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of IRB from SNEDDS compared with the pure drug solution. These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability of poorly water-soluble IRB. PMID:22171286

  18. Pathogenesis of atherosclerosis.

    PubMed

    Moore, S

    1985-12-01

    There is abundant evidence that changes in diet and various types of vessel wall injury can independently induce the growth of arterial lesions in experimental animals. These lesions closely resemble those found in humans with atherosclerosis. Whether endothelial injury or accumulation of lipoprotein in the arterial intima is the initial event, the progression of the disease is characterized by changes in the neointima that favor the deposition of lipid. The metabolism of proteoglycans may be especially important in this process; this is relevant to diabetes because changes in proteoglycan metabolism are associated with this disease. Insulin and growth hormone may favor the proliferation of smooth muscle cells in the arteries of diabetic patients. Many agents, which are potentially injurious to the endothelium, accentuate the response of the vessel wall to injury. Modifications of the thrombotic process, such as increased production of thromboxane by platelets, decreased production of prostacyclin by the endothelium, and increased production of von Willebrand factor further enhance the thrombotic process and may be important in the initiation and subsequent progression of atherosclerosis in diabetics. Alterations in lipoprotein metabolism may also facilitate the development of endothelial injury. PMID:3906356

  19. Atherosclerosis imaging and the Canadian Atherosclerosis Imaging Network.

    PubMed

    Tardif, Jean-Claude; Spence, J David; Heinonen, Therese M; Moody, Alan; Pressacco, Josephine; Frayne, Richard; L'allier, Philippe; Chow, Benjamin J W; Friedrich, Matthias; Black, Sandra E; Fenster, Aaron; Rutt, Brian; Beanlands, Rob

    2013-03-01

    Atherosclerosis exacts a large toll on society in the form of cardiovascular morbidity, mortality, and resource use and is exacerbated by the epidemics of obesity and diabetes. Consequently, there is a critical need for more-effective methods of diagnosis, treatment, and prevention of the complications of atherosclerosis. Careful and well-conducted large population studies are needed in order to truly understand the natural history of the disease, its imaging biomarkers, and their links to patient outcomes. The Canadian Atherosclerosis Imaging Network (CAIN) is a unique research network funded by the Canadian Institutes of Health Research and the Canada Foundation for Innovation and designed to address these needs and to enable large population-based imaging studies. The central objective of CAIN is to move innovations in imaging toward their broad application in clinical research and clinical practice for the improved evaluation of cardiac and neurologic vascular disease. CAIN is established as an international resource for studying the natural history, progression, and regression of atherosclerosis, as well as novel therapeutic interventions aimed at atherosclerosis. The network represents Canada's leading atherosclerosis imaging experts, embodying both basic imaging science and clinical imaging research. The network is improving methods of detection and treatment of atherosclerosis and, through a better understanding of the underlying disease itself, improving strategies for disease prevention. The benefits are expected to appear in the next 2 to 3 years. CAIN will drive innovation in imaging technology within the field of cardiology and neurology and improve health outcomes in Canada and worldwide. PMID:23245557

  20. [Dyslipidemia and atherosclerosis].

    PubMed

    Koba, Shinji; Hirano, Tsutomu

    2011-01-01

    Dyslipidemia is the most important risk factor for atherosclerosis. LDL, VLDL remnants, chylomicron remnants, small dense LDL(sdLDL), Lp(a), and oxidized LDL are pro-atherogenic and HDLs are anti-atherogenic lipoproteins. Not native LDL but modified LDL causes to the formation of foam cells. Among LDL particles, smaller denser LDLs are more susceptible to oxidation, and have longer residence time and higher affinity to the extracellular matrix. Delayed clearance of triglyceride-rich lipoproteins results in the formation of sdLDL which is associated with insulin resistance and postprandial hyperlipidemia. HDL plays an important role in the reverse cholesterol transport as well as having antiinflammatory and antioxidative effects. Dysfunction of HDL is an independent pro-atherogenic factor. In addition, decreased HDL-cholesterol is a feature of the metabolic dyslipidemia. PMID:21226274

  1. MicroRNAs and atherosclerosis

    PubMed Central

    Madrigal-Matute, Julio; Rotllan, Noemi; Aranda, Juan F.; Fernández-Hernando, Carlos

    2014-01-01

    MicroRNAs (miRNAs) are small (~22nucleotide) sequences of RNA that regulate gene expression at posttranscriptional level. MiRNA/mRNA base pairing complementarity provokes mRNA decay and consequent gene silencing. These endogenous gene expression inhibitors were primarily described in cancer but recent exciting findings have also demonstrated a key role in cardiovascular diseases (CVDs) including atherosclerosis. MiRNAs controls endothelial cell (EC), vascular smooth muscle cell (VSMC) and macrophage functions, and thereby regulate the progression of atherosclerosis. MiRNAs expression is modulated by different stimuli involved in every stage of atherosclerosis and conversely miRNAs modulates several pathways implicated in plaque development such as cholesterol metabolism. In the present review, we focus on the importance of miRNAs in atherosclerosis and we further discuss their potential use as biomarkers and therapeutic targets in CVDs. PMID:23512606

  2. Ultrasound imaging for risk assessment in atherosclerosis.

    PubMed

    Steinl, David C; Kaufmann, Beat A

    2015-01-01

    Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is rapidly rising in developing countries. Atherosclerosis is a disease that progresses silently over several decades before it results in the aforementioned clinical consequences. Therefore, there is a clinical need for imaging methods to detect the early stages of atherosclerosis and to better risk stratify patients. In this review, we will discuss how ultrasound imaging can contribute to the detection and risk stratification of atherosclerosis by (a) detecting advanced and early plaques; (b) evaluating the biomechanical consequences of atherosclerosis in the vessel wall; PMID:25938969

  3. Is atherosclerosis an autoimmune disease?

    PubMed Central

    2014-01-01

    Immunologic research into pathogenic mechanisms operating in autoimmune-mediated atherosclerosis initially focused on adaptive immunity. Current interest is directed to more basic inflammatory mechanisms. Chronic inflammation (innate immunity-associated) may trigger initial events that can lead to atherosclerotic cardiovascular disease. This chronic inflammation may start early in life and be perpetuated by classic atherosclerosis risk factors. Lipid peroxidation of low-density lipoprotein seems to be a key event in the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein triggers inflammatory and immunogenic events that promote endothelial dysfunction and the synthesis and secretion of pro-inflammatory cytokines, leading to an autoimmune response capable of accelerating the intracellular accumulation of lipids within atherosclerotic plaques. Oxidized low-density lipoprotein binds ?2-glycoprotein I to form circulating complexes found in both autoimmune and non-autoimmune atherosclerosis. It is likely that ?2-glycoprotein I and/or these complexes contribute to early atherogenesis by stimulating pro-inflammatory innate immunity through endogenous sensors and inflammasome/interleukin-1 pathways. We discuss the chronic inflammatory (innate) and autoimmune (adaptive) responses operating in atherosclerosis to discern the role of autoimmunity in atherosclerotic cardiovascular disease. PMID:24642015

  4. Who Is at Risk for Atherosclerosis?

    MedlinePLUS

    ... increases. Genetic or lifestyle factors cause plaque to build up in your arteries as you age. By the ... is atherosclerosis? 05/22/2014 Describes how the build-up of plaque over time causes atherosclerosis which can ...

  5. Atherosclerosis in parrots. A review.

    PubMed

    Bavelaar, F J; Beynen, A C

    2004-06-01

    Atherosclerosis is a common disease in parrots. The disease is found in all common parrot species, but especially in African Grey parrots and Amazons. It is a disease of older birds that is seen in both males and females. The most common sign is sudden death, but clinical symptoms that can be found include dyspnea, lethargy and nervous signs, such as paresis and collapses. Because the clinical signs are seldomly seen, it is difficult to diagnose atherosclerosis and therefore it is mostly an unexpected finding at necropsy. Age and species are determinants of atherosclerosis in parrots. Suggested risk factors include an elevated plasma cholesterol level, diet composition, social stress and inactivity, but research is needed to confirm this. PMID:15230050

  6. Chemokines in atherosclerosis: proceedings resumed.

    PubMed

    Zernecke, Alma; Weber, Christian

    2014-04-01

    Chemokines play important roles in atherosclerotic vascular disease. Expressed by not only cells of the vessel wall but also emigrated leukocytes, chemokines were initially discovered to direct leukocytes to sites of inflammation. However, chemokines can also exert multiple functions beyond cell recruitment. Here, we discuss novel and recently emerging aspects of chemokines and their involvement in atherosclerosis. While reviewing newly identified roles of chemokines and their receptors in monocyte and neutrophil recruitment during atherogenesis and atheroregression, we also revisit homeostatic functions of chemokines, including their roles in cell homeostasis and foam cell formation. The functional diversity of chemokines in atherosclerosis warrants a clear-cut mechanistic dissection and stage-specific assessment to better appreciate the full scope of their actions in vascular inflammation and to identify pathways that harbor the potential for a therapeutic targeting of chemokines in atherosclerosis. PMID:24436368

  7. Oxidative Stress, AntioxidantVitamins, and Atherosclerosis

    Microsoft Academic Search

    Charalambos Antoniades; Dimitris Tousoulis; Costas Tentolouris; Pavlos Toutouzas; Christodoulos Stefanadis

    2003-01-01

    Oxidative stress is involved in the pathogenesis of atherosclerosis, while a variety of antioxidants has been used in clinical studies, during the past few years, for the prevention and treatment of atherosclerosis. In small clinical studies it was found that both vitamins C and E may improve endothelial function in patients with risk factors for atherosclerosis such as diabetes mellitus,

  8. Intracranial Atherosclerosis: Incidence, Diagnosis and Treatment

    Microsoft Academic Search

    Jong S. Kim; Dong-Wha Kang; Sun U. Kwon

    2005-01-01

    Intracranial atherosclerosis is considered a cause of approximately 8% of all strokes in the western society. However, its frequency is much higher in Asian countries. In our hospital-based study, among the patients who had angiographic abnormalities, the frequency of intracranial atherosclerosis was approximately 70% far exceeding that of extratracranial atherosclerosis. Symptomatic atherosclerotic diseases were most often found in the middle

  9. Transmission of atherosclerosis susceptibility with gut microbial transplantation.

    PubMed

    Gregory, Jill C; Buffa, Jennifer A; Org, Elin; Wang, Zeneng; Levison, Bruce S; Zhu, Weifei; Wagner, Matthew A; Bennett, Brian J; Li, Lin; DiDonato, Joseph A; Lusis, Aldons J; Hazen, Stanley L

    2015-02-27

    Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n = 22 strains, r = 0.38; p = 0.0001). An atherosclerosis-prone and high TMAO-producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO-producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. Trimethylamine (TMA) and TMAO levels were initially higher in recipients on choline diet that received cecal microbes from C57BL/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden as compared with recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients and that tended to show coincident proportions with TMAO levels. Proportions of specific taxa were also identified that correlated with plasma TMAO levels in donors and recipients and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility. PMID:25550161

  10. ATP-binding cassette transporters, atherosclerosis, and inflammation.

    PubMed

    Westerterp, Marit; Bochem, Andrea E; Yvan-Charvet, Laurent; Murphy, Andrew J; Wang, Nan; Tall, Alan R

    2014-01-01

    Although recent genome-wide association studies have called into question the causal relationship between high-density lipoprotein (HDL) cholesterol levels and cardiovascular disease, ongoing research in animals and cells has produced increasing evidence that cholesterol efflux pathways mediated by ATP-binding cassette (ABC) transporters and HDL suppress atherosclerosis. These differing perspectives may be reconciled by a modified HDL theory that emphasizes the antiatherogenic role of cholesterol flux pathways, initiated in cells by ABC transporters. ABCA1 and ABCG1 control the proliferation of hematopoietic stem and multipotential progenitor cells in the bone marrow and hematopoietic stem and multipotential progenitor cell mobilization and extramedullary hematopoiesis in the spleen. Thus, activation of cholesterol efflux pathways by HDL infusions or liver X receptor activation results in suppression of hematopoietic stem and multipotential progenitor cell mobilization and extramedullary hematopoiesis, leading to decreased production of monocytes and neutrophils and suppression of atherosclerosis. In addition, macrophage-specific knockout of transporters has confirmed their role in suppression of inflammatory responses in the arterial wall. Recent studies have also shown that ABCG4, a close relative of ABCG1, controls platelet production, atherosclerosis, and thrombosis. ABCG4 is highly expressed in megakaryocyte progenitors, where it promotes cholesterol efflux to HDL and controls the proliferative responses to thrombopoietin. Reconstituted HDL infusions act in an ABCG4-dependent fashion to limit hypercholesterolemia-driven excessive platelet production, thrombosis, and atherogenesis, as occurs in human myeloproliferative syndromes. Activation of ABC transporter-dependent cholesterol efflux pathways in macrophages, hematopoietic stem and multipotential progenitor cells, or platelet progenitors by reconstituted HDL infusion or liver X receptor activation remain promising approaches to the treatment of human atherothrombotic diseases. PMID:24385509

  11. HDL and Inflammation in Atherosclerosis

    Microsoft Academic Search

    Lukas E. Spieker; Frank Ruschitzka; Thomas F. Luscher; Georg Noll

    2004-01-01

    Inflammation plays a major role in all phases of atherosclerosis. Stable plaques are characterized by a chronic inflammatory infil- trate, whereas vulnerable and ruptured plaques are character- ized by an ''active'' inflammation involved in the thinning of the fibrous cap, predisposing the plaque to rupture. Although a sin- gle vulnerable atherosclerotic plaque rupture may cause the event, there are many

  12. Atherosclerosis in parrots. A review

    Microsoft Academic Search

    F. J. Bavelaar; A. C. Beynen

    2004-01-01

    Atherosclerosis is a common disease in parrots. The disease is found in all common parrot species, but especially in African Grey parrots and Amazons. It is a disease of older birds that is seen in both males and females. The most common sign is sudden death, but clinical symptoms that can be found include dyspnea, lethargy and nervous signs, such

  13. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation. A prospective and randomized study

    Microsoft Academic Search

    Antonio H. Madrid; Manuel G. Bueno; Jose M. G. Rebollo

    2002-01-01

    Background—Data from studies of angiotensin-converting enzyme inhibitors provide evidence that the renin-angioten- sin-aldosterone system plays a role as a mediator of atrial remodeling in atrial fibrillation. The present study has evaluated the effect of treatment with the angiotensin I type 1 receptor blocker irbesartan on maintaining sinus rhythm after conversion from persistent atrial fibrillation. Methods and Results—To be included in

  14. Irbesartan is projected to be cost and life saving in a Spanish setting for treatment of patients with type 2 diabetes, hypertension, and microalbuminuria

    Microsoft Academic Search

    Andrew J. Palmer; LIEVEN ANNEMANS; STÉPHANE ROZE; PABLO LAPUERTA; ROLAND CHEN; SYLVIE GABRIEL; PAULO CARITA; Roger A. Rodby; DICK DE ZEEUW; HANS-HENRIK PARVING; FERNANDO DE ALVARO

    2005-01-01

    Irbesartan is projected to be cost and life saving in a Spanish setting for treatment of patients with type 2 diabetes, hypertension, and microalbuminuria.ObjectivesThe purpose of this study was to project the cumulative incidence of end-stage renal disease (ESRD), life expectancy, and costs in a Spanish setting of treating patients with diabetes, hypertension, and microalbuminuria with either standard hypertension treatment

  15. Insights into Atherosclerosis Using Nanotechnology

    PubMed Central

    Linton, MacRae F.; Fazio, Sergio; Haselton, Frederick R.

    2010-01-01

    A developing forefront in vascular disease research is the application of nanotechnology, the engineering of devices at the molecular scale, for diagnostic and therapeutic applications in atherosclerosis. Promising research in this field over the past decade has resulted in the preclinical validation of nanoscale devices that target cellular and molecular components of the atherosclerotic plaque, including one of its prominent cell types, the macrophage. Nanoscale contrast agents targeting constituents of plaque biology have been adapted for application in multiple imaging modalities, leading toward more detailed diagnostic readouts, whereas nanoscale drug delivery devices can be tailored for site-specific therapeutic activity. This review highlights recent progress in utilizing nanotechnology for the clinical management of atherosclerosis, drawing upon recent preclinical studies relevant to diagnosis and treatment of the plaque and promising future applications. PMID:20425261

  16. Atherosclerosis: immune and inflammatory aspects.

    PubMed

    Reiss, Allison B; Glass, Amy D

    2006-04-01

    This review article discusses the historical origin of our continuously evolving model of the etiology of atherosclerotic cardiovascular disease. The basic molecular biologic concepts underlying the development of coronary artery disease and the dynamic connection between the immune system and arterial integrity are explored. Emphasis is placed on the role of inflammation as a driving force in the process of atherosclerosis and vascular endothelium as a modulating factor in the pathogenesis of coronary artery disease. PMID:16948395

  17. Suppressor of cytokine signaling and accelerated atherosclerosis in kidney disease.

    PubMed

    Wesoly, Joanna; Sikorski, Krzysztof; Lee, Chien-Kuo; Bluyssen, Hans A R

    2010-01-01

    The prevalence of cardiovascular disease in patients with renal failure is extremely high and accounts for a large part of the morbidity and mortality. Inflammation participates importantly in host defense against infectious agents and injury, but also contributes to the pathophysiology of many diseases, including cardiovascular atherosclerosis, which is a main problem in patients with renal failure. Recruitment of blood leukocytes to the injured vascular endothelium characterizes the initiation and progression of atherosclerosis and involves many inflammatory mediators, modulated by cells of both innate and adaptive immunity. Excessive inflammatory and immune responses, communicated by these different cell types, are driven by inflammatory cytokines that promote associated tissue damage if cytokine signaling pathways remain unregulated. Thus, pathways capable of suppressing proinflammatory cytokine signaling hold the potential to limit life-threatening cardiovascular events caused by atherogenesis. Suppressor of cytokine signaling (SOCS) are a family of intracellular proteins, several of which have emerged as key physiological regulators of cytokine-mediated homeostasis, including innate and adaptive immunity. Accumulating evidence supports the idea that dysregulation of cytokine signaling by differential SOCS expression is involved in the pathogenesis of various inflammatory, and immunological diseases, including atherosclerosis. Based on recent observations, in which SOCS expression levels are profoundly altered in kidney disease, we discuss the possibilities of SOCS as new intracellular markers of inflammation as well as their potential atherogenic properties in renal failure related cardiovascular disease. PMID:20725646

  18. Plasmacytoid dendritic cells in atherosclerosis.

    PubMed

    Döring, Yvonne; Zernecke, Alma

    2012-01-01

    Atherosclerosis, a chronic inflammatory disease of the vessel wall and the underlying cause of cardiovascular disease, is initiated and maintained by innate and adaptive immunity. Accumulating evidence suggests an important contribution of autoimmune responses to this disease. Plasmacytoid dendritic cells (pDCs), a specialized cell type known to produce large amounts of type I interferons (IFNs) in response to bacterial and viral infections, have recently been revealed to play important roles in atherosclerosis. For example, the development of autoimmune complexes consisting of self-DNA and antimicrobial peptides, which trigger chronic type I IFN production by pDCs, promote early atherosclerotic lesion formation. pDCs and pDC-derived type I IFNs can also induce the maturation of conventional DCs and macrophages, and the development of autoreactive B cells and antibody production. These mechanisms, known to play a role in the pathogenesis of other autoimmune diseases such as systemic lupus erythematosus and psoriasis, may also affect the development and progression of atherosclerotic lesion formation. This review discusses emerging evidence showing a contribution of pDCs in the onset and progression of atherosclerosis. PMID:22754539

  19. Ultrasound Imaging for Risk Assessment in Atherosclerosis

    PubMed Central

    Steinl, David C.; Kaufmann, Beat A.

    2015-01-01

    Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is rapidly rising in developing countries. Atherosclerosis is a disease that progresses silently over several decades before it results in the aforementioned clinical consequences. Therefore, there is a clinical need for imaging methods to detect the early stages of atherosclerosis and to better risk stratify patients. In this review, we will discuss how ultrasound imaging can contribute to the detection and risk stratification of atherosclerosis by (a) detecting advanced and early plaques; (b) evaluating the biomechanical consequences of atherosclerosis in the vessel wall; (c) assessing plaque neovascularization and (d) imaging the expression of disease-relevant molecules using molecular imaging. PMID:25938969

  20. Novel markers of inflammation in atherosclerosis

    Microsoft Academic Search

    Salim S. Virani; Venkateshwar R. Polsani; Vijay Nambi

    2008-01-01

    Inflammation plays a key role in the pathogenesis of atherosclerosis. Understanding the process of inflammation as it pertains\\u000a to atherosclerosis has provided researchers with multiple opportunities to identify novel markers for use in cardiovascular\\u000a disease management. This article discusses the inflammatory cascade as it pertains to atherosclerosis and some of the well-studied\\u000a markers of inflammation. It also discusses the limitations

  1. Cathepsin G activity lowers plasma LDL and reduces atherosclerosis.

    PubMed

    Wang, Jing; Sjöberg, Sara; Tang, Ting-Ting; Oörni, Katariina; Wu, Wenxue; Liu, Conglin; Secco, Blandine; Tia, Viviane; Sukhova, Galina K; Fernandes, Cleverson; Lesner, Adam; Kovanen, Petri T; Libby, Peter; Cheng, Xiang; Shi, Guo-Ping

    2014-11-01

    Cathepsin G (CatG), a serine protease present in mast cells and neutrophils, can produce angiotensin-II (Ang-II) and degrade elastin. Here we demonstrate increased CatG expression in smooth muscle cells (SMCs), endothelial cells (ECs), macrophages, and T cells from human atherosclerotic lesions. In low-density lipoprotein (LDL) receptor-deficient (Ldlr(-/-)) mice, the absence of CatG reduces arterial wall elastin degradation and attenuates early atherosclerosis when mice consume a Western diet for 3months. When mice consume this diet for 6months, however, CatG deficiency exacerbates atherosclerosis in aortic arch without affecting lesion inflammatory cell content or extracellular matrix accumulation, but raises plasma total cholesterol and LDL levels without affecting high-density lipoprotein (HDL) or triglyceride levels. Patients with atherosclerosis also have significantly reduced plasma CatG levels that correlate inversely with total cholesterol (r=-0.535, P<0.0001) and LDL cholesterol (r=-0.559, P<0.0001), but not with HDL cholesterol (P=0.901) or triglycerides (P=0.186). Such inverse correlations with total cholesterol (r=-0.504, P<0.0001) and LDL cholesterol (r=-0.502, P<0.0001) remain significant after adjusting for lipid lowering treatments among this patient population. Human CatG degrades purified human LDL, but not HDL. This study suggests that CatG promotes early atherogenesis through its elastinolytic activity, but suppresses late progression of atherosclerosis by degrading LDL without affecting HDL or triglycerides. PMID:25092171

  2. 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.

  3. 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 and specifically in atherogenesis, be- cause apoptosis is a prominent feature of late lesions. KEYWORDS: scavenger-534- 2005. dsteinberg@ucsd.edu #12;215BOULLIER et al.: SCAVENGER RECEPTORS, LDL, AND ATHEROSCLEROSIS

  4. 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

  5. Vitamin D Deficiency Induces High Blood Pressure and Accelerates Atherosclerosis in Mice

    PubMed Central

    Oh, Jisu; Riek, Amy E.; Chin, Kathleen; Garcia, Miguel; Bernal-Mizrachi, Carlos

    2013-01-01

    Multiple epidemiological studies link vitamin D deficiency to increased cardiovascular disease (CVD), but causality and possible mechanisms underlying these associations are not established. To clarify the role of vitamin D-deficiency in CVD in vivo, we generated mouse models of diet-induced vitamin D deficiency in two backgrounds (LDL receptor- and ApoE-null mice) that resemble humans with diet-induced hypertension and atherosclerosis. Mice were fed vitamin D-deficient or -sufficient chow for 6 weeks and then switched to high fat (HF) vitamin D-deficient or –sufficient diet for 8–10 weeks. Mice with diet-induced vitamin D deficiency showed increased systolic and diastolic blood pressure, high plasma renin, and decreased urinary sodium excretion. Hypertension was reversed and renin was suppressed by returning chow-fed vitamin D-deficient mice to vitamin D-sufficient chow diet for 6 weeks. On a HF diet, vitamin D-deficient mice had ?2-fold greater atherosclerosis in the aortic arch and ?2–8-fold greater atherosclerosis in the thoracic and abdominal aorta compared to vitamin D-sufficient mice. In the aortic root, HF-fed vitamin D-deficient mice had increased macrophage infiltration with increased fat accumulation and endoplasmic reticulum (ER) stress activation, but a lower prevalence of the M1 macrophage phenotype within atherosclerotic plaques. Similarly, peritoneal macrophages from vitamin D-deficient mice displayed an M2-predominant phenotype with increased foam cell formation and ER stress. Treatment of vitamin D-deficient mice with the ER stress reliever PBA during HF feeding suppressed atherosclerosis, decreased peritoneal macrophage foam cell formation, and downregulated ER stress proteins without changing blood pressure. Thus, we suggest that vitamin D deficiency activates both the renin angiotensin system and macrophage ER stress to contribute to the development of hypertension and accelerated atherosclerosis, highlighting vitamin D replacement as a potential therapy to reduce blood pressure and atherosclerosis. PMID:23349943

  6. 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.

  7. 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 ...

  8. Vasoprotective Effects of Urocortin 1 against Atherosclerosis In Vitro and In Vivo

    PubMed Central

    Shirai, Remina; Watanabe, Rena; Yamamoto, Keigo; Watanabe, Kaho; Nohtomi, Kyoko; Hirano, Tsutomu; Watanabe, Takuya

    2014-01-01

    Aim Atherosclerosis is the complex lesion that consists of endothelial inflammation, macrophage foam cell formation, vascular smooth muscle cell (VSMC) migration and proliferation, and extracellular matrix production. Human urocortin 1 (Ucn1), a 40-amino acid peptide member of the corticotrophin-releasing factor/urotensin I family, has potent cardiovascular protective effects. This peptide induces potent and long-lasting hypotension and coronary vasodilation. However, the relationship of Ucn1 with atherosclerosis remains unclear. The present study was performed to clarify the effects of Ucn1 on atherosclerosis. Methods We assessed the effects of Ucn1 on the inflammatory response and proliferation of human endothelial cells (ECs), human macrophage foam cell formation, migration and proliferation of human VSMCs, extracellular matrix expression in VSMCs, and the development of atherosclerosis in apolipoprotein E-deficient (Apoe?/?) mice. Results Ucn1 significantly suppressed cell proliferation without inducing apoptosis, and lipopolysaccharide-induced up-regulation of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 in human ECs. Ucn1 significantly reduced oxidized low-density lipoprotein-induced foam cell formation with a significant down-regulation of CD36 and acyl-CoA:cholesterol acyltransferase 1 in human monocyte-derived macrophages. Ucn1 significantly suppressed the migration and proliferation of human VSMCs and increased the activities of matrix metalloproteinase-2 (MMP2) and MMP9 in human VSMCs. Intraperitoneal injection of Ucn1 into Apoe?/? mice for 4 weeks significantly retarded the development of aortic atherosclerotic lesions. Conclusions This study provided the first evidence that Ucn1 prevents the development of atherosclerosis by suppressing EC inflammatory response and proliferation, macrophage foam cell formation, and VSMC migration and proliferation. Thus, Ucn1 could serve as a novel therapeutic target for atherosclerotic cardiovascular diseases. PMID:25462164

  9. Perivascular Adipose Tissue-Derived Adiponectin Inhibits Collar-Induced Carotid Atherosclerosis by Promoting Macrophage Autophagy

    PubMed Central

    Li, Changlong; Wang, Zhijian; Wang, Chunxiao; Ma, Qian; Zhao, Yingxin

    2015-01-01

    Objectives Adiponectin (APN) secreted from perivascular adipose tissue (PVAT) is one of the important anti-inflammatory adipokines to inhibit the development of atherosclerosis, but the underlying mechanism has not been clarified. In this study, we aimed to elucidate how APN regulates plaque formation in atherosclerosis. Methods and Results To assess the role of APN secreted by PVAT in atherosclerosis progression, we performed PVAT transplantation experiments on carotid artery atherosclerosis model: ApoE knockout (ApoE?/?) mice with a perivascular collar placement around the left carotid artery in combination with a high-fat diet feeding. Our results show that the ApoE?/? mice with PVAT derived from APN knockout (APN?/?) mice exhibited accelerated plaque volume formation compared to ApoE?/? mice transplanted with wild-type littermate tissue. Conversely, autophagy in macrophages was significantly attenuated in ApoE?/? mice transplanted with APN-/- mouse-derived PVAT compared to controls. Furthermore, in vitro studies indicate that APN treatment increased autophagy in primary macrophages, as evidenced by increased LC3-I processing and Beclin1 expression, which was accompanied by down-regulation of p62. Moreover, our results demonstrate that APN promotes macrophage autophagy via suppressing the Akt/FOXO3a signaling pathway. Conclusions Our results indicate that PVAT-secreted APN suppresses plaque formation by inducing macrophage autophagy. PMID:26020520

  10. A proteomic portrait of atherosclerosis.

    PubMed

    Eberini, Ivano; Wait, Robin; Calabresi, Laura; Sensi, Cristina; Miller, Ingrid; Gianazza, Elisabetta

    2013-04-26

    We have arranged in this review the main evidence about proteome alterations in different cell and body fluid compartments along the progression of atherosclerosis. With time the description of the molecular phenomena is becoming more and more detailed yet the complex interrelationships among different factors are still elusive and previously neglected aspects (such as size for lipoprotein particles) emerge as not less relevant than the absolute abundance of individual proteins. Physiological limits to the kinetics of protein distribution through the biological fluids seem to hinder the early diagnosis of acute conditions through plasma analysis but suggest urine analysis as a workable alternative for the assessment of chronic conditions. The survey of literature data is complemented with a few unpublished results from our laboratories, featuring 2DE maps of the proteins extracted from human thrombi. PMID:23435058

  11. Atherosclerosis in Systemic Lupus Erythematosus

    PubMed Central

    Stojan, George; Petri, Michelle

    2015-01-01

    Accelerated atherosclerosis and its long-term sequelae are a major cause of late mortality among patients with systemic lupus erythematosus (SLE). Traditional Framingham risk factors such as hypertension, hypercholesterolemia, diabetes, and smoking do not account in entirety for this risk. SLE specific factors like disease activity and duration, use of corticosteroids, presence of antiphospholipid antibodies, and others are important risk factors. SLE is considered a coronary heart disease; equivalent and aggressive management of all traditional risk factors is recommended. Despite their role in primary and secondary prevention in the general population, statins seem to have no effect on cardiovascular outcomes in adult or pediatric SLE populations. The use of hydroxychloroquine has a cardioprotective effect, and mycophenolate mofetil may reduce cardiovascular events based on basic science data and data from the transplant population. The role of vitamin D supplementation and treatment of hyperhomocysteinemia remain controversial, but due to the safety of therapy and the potential benefit, they remain as optional therapies. PMID:23792700

  12. [¹?F]-fluorodeoxyglucose PET imaging of atherosclerosis.

    PubMed

    Blomberg, Björn A; Høilund-Carlsen, Poul Flemming

    2015-01-01

    [(18)F]-fluorodeoxyglucose PET ((18)FDG PET) imaging has emerged as a promising tool for assessment of atherosclerosis. By targeting atherosclerotic plaque glycolysis, a marker for plaque inflammation and hypoxia, (18)FDG PET can assess plaque vulnerability and potentially predict risk of atherosclerosis-related disease, such as stroke and myocardial infarction. With excellent reproducibility, (18)FDG PET can be a surrogate end point in clinical drug trials, improving trial efficiency. This article summarizes key findings in the literature, discusses limitations of (18)FDG PET imaging of atherosclerosis, and reports recommendations to optimize imaging protocols. PMID:25455876

  13. Neutrophils in atherosclerosis. A brief overview.

    PubMed

    Hartwig, H; Silvestre Roig, C; Daemen, M; Lutgens, E; Soehnlein, O

    2015-05-01

    Atherosclerosis is a chronic inflammation of the arterial wall and the continuous infiltration of leukocytes into the plaque enhances the progression of the lesion. Because of the scarce detection of neutrophils in atherosclerotic plaques compared to other immune cells, their contribution was largely neglected. However, in the last years studies have accumulated pointing towards the contribution of neutrophils to atherogenesis. In addition, studies are emerging implying a role for neutrophils in advanced atherosclerosis and/or plaque destabilization. Thus, this brief review delivers an overview of the role of neutrophils during early and late stage atherosclerosis. PMID:25385255

  14. Predictors of blood pressure response to angiotensin receptor blocker/diuretic combination therapy: a secondary analysis of the irbesartan/hydrochlorothiazide blood pressure reductions in diverse patient populations (INCLUSIVE) study.

    PubMed

    Saunders, Elijah; Cable, Greg; Neutel, Joel

    2008-01-01

    The secondary analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) clinical trial investigated whether baseline demographic and clinical variables are predictive of different degrees of blood pressure reduction following an angiotensin II receptor blocker/diuretic treatment regimen. Irbesartan/hydrochlorothiazide and other angiotensin receptor blocker combinations with a diuretic have been shown to be effective in reducing systolic blood pressure in a diverse patient population previously uncontrolled on monotherapy. Ordinary least squares regression analysis was performed on the intent-to-treat population of the INCLUSIVE study to identify variables predictive of variations in blood pressure changes in response to irbesartan/hydrochlorothiazide combination therapy. Higher baseline systolic blood pressure, female sex, type 2 diabetes, and statin therapy were found to be predictive of additional blood pressure lowering with this combination. The impact of higher baseline systolic blood pressure and diabetic state on changes in systolic blood pressure were diminished in female patients compared with male patients. In conclusion, a significant correlation may exist between certain clinical/demographic characteristics and the extent of the therapeutic response with irbesartan/hydrochlorothiazide treatment. PMID:18174768

  15. The efficacy and safety of initial use of irbesartan/hydrochlorothiazide fixed-dose combination in hypertensive patients with and without high cardiovascular risk.

    PubMed

    Weir, Matthew R; Neutel, Joel M; Bhaumik, Amitabha; De Obaldia, Maria Elena; Lapuerta, Pablo

    2007-12-01

    A post hoc pooled analysis of 2 multicenter, randomized, double-blind, active-controlled force-titration studies assessed the antihypertensive efficacy and tolerability of 7 to 8 weeks' once-daily fixed-dose irbesartan/hydrochlorothiazide (HCTZ) 300/25 mg in 796 stage 1 or 2 hypertensive patients according to age (65 years or older or younger than 65) (n=121 or 675) and presence or absence of obesity (n=378 or 414), type 2 diabetes (n=99 or 697), and high World Health Organization-defined cardiovascular risk (n=593 or 202). Systolic/diastolic blood pressure reductions (27-31/16-22 mm Hg) were similar regardless of age, obesity, and type 2 diabetes status and were greater in high- vs low-risk patients. Dizziness (2.0%-3.7%), hypotension (0%-0.7%), and syncope (0%) were rare and not centered in any subgroup. There was no hypotension in the elderly or in type 2 diabetics. Irbesartan/HCTZ provided consistent blood pressure lowering and tolerability regardless of age, obesity, and type 2 diabetes and greater efficacy in patients with high cardiovascular risk. PMID:18046109

  16. Metabolic Syndrome: The Danger Signal in Atherosclerosis

    PubMed Central

    Mathieu, Patrick; Pibarot, Philippe; Després, Jean-Pierre

    2006-01-01

    Atherosclerosis is a chronic inflammatory disease characterized by infiltration of blood vessels by lipids and leukocytes. There is a growing body of evidence that among risk factors that promote atherosclerosis, the metabolic syndrome is a powerful and prevalent predictor of cardiovascular events. The systemic inflammatory process associated with the metabolic syndrome has numerous deleterious effects that promote plaque activation, which is responsible for clinical events. Interactions between the innate immune system with lipid-derived products seem to play a major role in the pathophysiology of atherosclerosis in relation with the metabolic syndrome. The multiple links among adipose tissue, the vascular wall, and the immune system are the topics of this review, which examines the roles of oxidized low-density lipoprotein, inflammatory cytokines, and adipokines in triggering and perpetuating a danger signal response that promotes the development of atherosclerosis. Furthermore, therapeutic options that specifically target the metabolic syndrome components are reviewed in light of recent developments. PMID:17326334

  17. Neutrophils in atherosclerosis: from mice to man.

    PubMed

    Döring, Yvonne; Drechsler, Maik; Soehnlein, Oliver; Weber, Christian

    2015-02-01

    Infiltration of leukocyte subsets is a driving force of atherosclerotic lesion growth, and during the past decade, neutrophils have received growing attention in chronic inflammatory processes, such as atherosclerosis. Equipped with various ready to be released mediators, evolved to fight invading pathogens, neutrophils may also hold key functions in affecting sterile inflammation, such as in atherosclerosis. Many of their secretion products might instruct or activate other immune cells (particularly monocytes) to, for example, enter atherosclerotic lesions or release proinflammatory mediators. Despite the emerging evidence for the mechanistic contribution of neutrophils to early atherosclerosis in mice, their role in human atherogenesis, atheroprogression, and atherosclerotic plaque destabilization is still poorly understood. This brief review will summarize latest findings on the role of neutrophils in atherosclerosis and will pay special attention to studies describing a translation approach by combining measurements in mouse and human. PMID:25147339

  18. 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

  19. Increased blood plasminogen activator inhibitor-1 and intercellular adhesion molecule-1 as possible risk factors of atherosclerosis in Werner syndrome.

    PubMed

    Murano, S; Nakazawa, A; Saito, I; Masuda, M; Morisaki, N; Akikusa, B; Tsuboyama, T; Saito, Y

    1997-01-01

    Werner syndrome is a rare premature aging syndrome accompanied by severe atherosclerosis. The etiology of atherosclerosis is suspected to be due to its complications, namely diabetes mellitus, hyperinsulinemia and hyperlipidemia. But from an autopsy case we found that some other risk factors may be involved in the mechanism of atherosclerosis in this syndrome. Previously we revealed that the plasminogen activator inhibitor-1 (PAI-1) gene was being overexpressed in skin fibroblasts from a patient with this syndrome. PAI-1 is a potent inhibitor of tissue plasminogen activator and a possible risk factor of atherosclerosis. This led us to assess the plasma concentration of PAI-1. Our working hypothesis was that the PAI-1 gene was upregulated or not fully suppressed in cells responsible for the production of PAI-1 in plasma as well as in fibroblasts. The results show a high concentration of plasma PAI-1. One of the well-known physiological substances that induce the PAI-1 gene is tumor necrosis factor-alpha, which also induces other possible risk factors of atherosclerosis, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1. We found the serum concentrations of ICAM-1 to be elevated in patients with this syndrome. We conclude that high concentrations of PAI-1 and ICAM-1 in blood may be one of the potent causes of severe atherosclerosis in Werner syndrome. PMID:9187938

  20. Hyperimmunization of apo-E-deficient mice with homologous malondialdehyde low-density lipoprotein suppresses early atherogenesis

    Microsoft Academic Search

    Jacob George; Arnon Afek; Boris Gilburd; Hana Levkovitz; Aviv Shaish; Iris Goldberg; Yuri Kopolovic; Georg Wick; Yehuda Shoenfeld; Dror Harats

    1998-01-01

    The role of the immune system in modulating atherosclerosis has recently been the subject of intensive research. Several previous authors have put forward a paradigm of the autoimmune process occurring in the vicinity of the plaque. Two recent studies have shown that immunization of rabbits with homologous modified low-density lipoprotein (LDL) led to suppression of atherosclerosis. In the current study

  1. Antioxidant Status in Peripheral Vascular Atherosclerosis

    Microsoft Academic Search

    B. Porcelli; L. Terzuoli; B. Frosi; C. Felici; L. Barabesi; S. Naddeo; S. Meini; D. Pieragalli; I. Baldi; G. de Donato; E. Marinello; M Giubbolini; C. Setacci

    2005-01-01

    Although involvement of free radicals in atherosclerosis is well researched, few parameters indicative of the body’s antioxidant\\u000a capacity have been analyzed in this disease. We analyzed total antioxidant capacity and a series of antioxidants in the plasma\\u000a of subjects with atherosclerosis. The information obtained could help to understand the role of antioxidants in this disorder\\u000a and to evaluate their potential

  2. Complications of aortic atherosclerosis: Atheroemboli and thromboemboli

    Microsoft Academic Search

    Theresa A. Molisse; Paul A. Tunick; Itzhak Kronzon

    2007-01-01

    Opinion statement  Patients with severe aortic atherosclerosis are at high risk for stroke and other embolic complications. Therapy to prevent\\u000a emboli from aortic plaque is not yet established. Therefore, patients with atherosclerosis or risk factors for embolic disease\\u000a should be identified and treated aggressively. Aspirin, smoking cessation, and control of blood pressure and glucose are important.\\u000a Retrospective data in patients with

  3. Homocysteine: Role and implications in atherosclerosis

    Microsoft Academic Search

    Sasidhar Guthikonda; William G. Haynes

    2006-01-01

    Hyperhomocysteinemia promotes atherosclerosis and is most commonly caused by B-vitamin deficiencies, especially folic acid,\\u000a B6, and B12; genetic disorders; certain drugs; and renal impairment. Elevated homocysteine promotes atherosclerosis through increased\\u000a oxidant stress, impaired endothelial function, and induction of thrombosis. Prospective studies have shown that elevated plasma\\u000a homocysteine concentrations increase risk of cardiovascular disease by twofold and risk of cerebrovascular disease

  4. Environmental carcinogens and mutational pathways in atherosclerosis.

    PubMed

    Pulliero, A; Godschalk, R; Andreassi, M G; Curfs, D; Van Schooten, F J; Izzotti, A

    2015-05-01

    Atherosclerosis is associated with DNA damage in both circulating and vessel-wall cells and DNA adducts derived from exposure to environmental mutagens are abundant in atherosclerotic vessels. Environmental chemical carcinogens identified as risk factor for atherosclerosis include polycyclic aromatic hydrocarbons (benzo(a)pyrene, dimethylbenz(a)anthracene, beta-naphthoflavone, pyrene, 3-methylcolanthrene), arsenic, cadmium, 1,3-butadiene, cigarette smoke. Accordingly, polymorphisms of genes encoding for phase I/II metabolic reaction and DNA repair are risk factor for cardiovascular diseases, although their role is negligible as compared to other risk factors. The pathogenic relevance of mutation-related molecular damage in atherosclerosis has been demonstrated in experimental animal models involving the exposure to chemical mutagens. The relevance of mutation-related events in worsening atherosclerosis prognosis has been demonstrated in human clinical studies mainly as referred to mitochondrial DNA damage. Atherosclerosis is characterized by the occurrence of high level of oxidative damage in blood vessel resulting from both endogenous and exogenous sources. Mitochondrial damage is a main endogenous source of oxidative stress whose accumulation causes activation of intrinsic apoptosis through BIRC2 inhibition and cell loss contributing to plaque development and instability. Environmental physical mutagens, including ionizing radiation, are a risk factor for atherosclerosis even at the low exposure dose occurring in case of occupational exposure or the high exposure doses occurring during radiotherapy. Conversely, the role of exciting UV radiation in atherosclerosis is still uncertain. This review summarizes the experimental and clinical evidence supporting the pathogenic role of mutation-related pathway in atherosclerosis examining the underlying molecular mechanisms. PMID:25704189

  5. Positron emission tomography imaging of atherosclerosis.

    PubMed

    Orbay, Hakan; Hong, Hao; Zhang, Yin; Cai, Weibo

    2013-01-01

    Atherosclerosis-related cardiovascular events are the leading causes of death in the industrialized world. Atherosclerosis develops insidiously and the initial manifestation is usually sudden cardiac death, stroke, or myocardial infarction. Molecular imaging is a valuable tool to identify the disease at an early stage before fatal manifestations occur. Among the various molecular imaging techniques, this review mainly focuses on positron emission tomography (PET) imaging of atherosclerosis. The targets and pathways that have been investigated to date for PET imaging of atherosclerosis include: glycolysis, cell membrane metabolism (phosphatidylcholine synthesis), integrin ?v?3, low density lipoprotein (LDL) receptors (LDLr), natriuretic peptide clearance receptors (NPCRs), fatty acid synthesis, vascular cell adhesion molecule-1 (VCAM-1), macrophages, platelets, etc. Many PET tracers have been investigated clinically for imaging of atherosclerosis. Early diagnosis of atherosclerotic lesions by PET imaging can help to prevent the premature death caused by atherosclerosis, and smooth translation of promising PET tracers into the clinic is critical to the benefit of patients. PMID:24312158

  6. Superoxide and Peroxynitrite in Atherosclerosis

    NASA Astrophysics Data System (ADS)

    White, C. Roger; Brock, Tommy A.; Chang, Ling-Yi; Crapo, James; Briscoe, Page; Ku, David; Bradley, William A.; Gianturco, Sandra H.; Gore, Jeri; Freeman, Bruce A.; Tarpey, Margaret M.

    1994-02-01

    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 (O^-_2), 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 O^-_2. 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 ? 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 O^-_2 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.

  7. [Arterial elastin in atherosclerosis and hypertensive disease].

    PubMed

    Anestiadi, V Kh; Zota, E G

    1975-01-01

    Elasticity and elastin of arteries in 106 dead people aged 14--74 years were investigated using physico-chemical methods. Depending on the character of morphological manifestations, aortas and arteries were divided into following groups: 1) without morphological manifestations of atherosclerosis; 2) affected by atherosclerosis; 3) vessels of patients who had suffered from atherosclerosis and hypertensive disease; 4) aortas and arteries of patients with atherosclerosis in combination with other somatic diseases. In atherosclerosis and hypertensive disease there were observed specific shifts in the character and intensity of fluorescence of elastin and elasticity as a whole. The intensity of primary fluorescence as an atherosclerotic process progressed and in concomitant hypertensive disease gradually changed. In atherosclerosis there were noted changes in transversal bands in elastin. The growth of transversal bands and intensity of fluorescence were found to be interrelated. Optical density of dissolved elastin with wave lengths (lambda) 240, 260, 280, 300, 320, 360, 400, 490 nm and pH 7.7 and 8.6 was studied. The peak of intensity of absorption of the solution of elastin in all groups referred to above was noted at the wave length lambda=240 nm. Amino-acid composition of dissolved elastin was also studied. It was established that as the process of atherosclerosis progressed, the content of lysine in the wall increased depending on the phase of the process -- lipoidosis, atheromatosis, etc. In the vascular wall there were observed changes in monoamino-oxidase, the latter being of particular importance for maintaining the level of cuprum in tissues. PMID:1180699

  8. Nanoparticles containing a liver X receptor agonist inhibit inflammation and atherosclerosis.

    PubMed

    Zhang, Xue-Qing; Even-Or, Orli; Xu, Xiaoyang; van Rosmalen, Mariska; Lim, Lucas; Gadde, Suresh; Farokhzad, Omid C; Fisher, Edward A

    2015-01-28

    Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, it is demonstrated that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP-LXR) exert anti-inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs are engineered through self-assembly of a biodegradable diblock poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) copolymer. NP-LXR is significantly more effective than free GW3965 at inducing LXR-target gene expression and suppressing inflammatory factors in macrophages in vitro and in vivo. Additionally, the NPs elicit negligible lipogenic gene stimulation in the liver. Using the Ldlr (-/-) mouse model of atherosclerosis, abundant colocalization of fluorescently labeled NPs within plaque macrophages following systemic administration is seen. Notably, six intravenous injections of NP-LXR over 2 weeks markedly reduce the CD68-positive cell (macrophage) content of plaques (by 50%) without increasing total cholesterol or triglycerides in the liver and plasma. Together, these findings identify GW3965-encapsulated PLGA-b-PEG NPs as a promising nanotherapeutic approach to combat atherosclerosis, providing the benefits of LXR agonists without their adverse effects on hepatic and plasma lipid metabolism. PMID:25156796

  9. 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

  10. Atherosclerosis and tumor suppressor molecules (review).

    PubMed

    Suzuki, Miho; Minami, Akari; Nakanishi, Atsuko; Kobayashi, Keiko; Matsuda, Satoru; Ogura, Yasunori; Kitagishi, Yasuko

    2014-10-01

    Atherosclerosis, the major cause of heart attack and stroke, is a chronic inflammatory disease characterized by the formation of atherosclerotic plaque. Oxidized low-density lipoprotein through increased oxidative stress has been identified as one of the primary factors responsible for atherogenesis. Cell proliferation and death are key processes in the progression of atherosclerosis. The oxidative environment in areas of lipid accumulation is mainly created by the production of reactive oxygen species, which are assumed to mediate vascular tissue injury. Oxidative DNA damage and levels of DNA repair are reduced during dietary lipid lowering. The tumor suppressor molecules play a pivotal role in regulating cell proliferation, DNA repair and cell death, which are important processes in regulating the composition of atherosclerotic plaque. Accordingly, in this review, we discuss the fundamental role of tumor suppressor molecules in regulating atherogenesis. In particular, we discuss how tumor suppressor molecules are activated in the complex environment of atherosclerotic plaque, and regulate growth arrest, cell senescence and the apoptosis of vascular smooth muscle cells, which may protect against the progression of atherosclerosis. In addition, we discuss promising alternatives to the use of medications (such as statin) against atherosclerosis, namely diet, with the use of plant-derived supplements to modulate the expression and/or activity of tumor suppressor molecules. We also summarize the progress of research made on herbs with a focus on the modulatory roles of tumor suppressors, and on the molecular mechanisms underlying the prevention if atherosclerosis, supporting designs for further research in this field. PMID:25069568

  11. Genetic Modifiers of Atherosclerosis in Mice

    PubMed Central

    Knowles, Joshua W.; Maeda, Nobuyo

    2009-01-01

    Atherosclerosis is a complex, multifactorial disease with both genetic and environmental determinants. Experimental investigation of the effects of these determinants on the development and progression of atherosclerosis has been greatly facilitated by the use of targeted mouse models of the disease, particularly those resulting from the absence of functional genes for apolipoprotein E or the low density lipoprotein receptor (LDLR). This review focuses on the influence on atherosclerosis of combining apoE or LDLR deficiencies with factors affecting atherogenesis, including (1) inflammatory processes, (2) glucose metabolism, (3) blood pressure, and (4) coagulation and fibrinolysis. We also discuss the general problem of using the mouse to test the effects on atherogenesis of human polymorphic variations and future ways of enhancing the usefulness of these mouse models. PMID:11073835

  12. Role of endothelial lipase in atherosclerosis.

    PubMed

    Huang, Ji; Qian, Hai-Yan; Li, Zhi-Zhong; Zhang, Jing-Mei; Wang, Su; Tao, Ying; Gao, Yu-Long; Yin, Cheng-Qian; Que, Bin; Sun, Tao; Zhao, Zhan-Yong; Li, Zhao

    2010-07-01

    Endothelial lipase, which is a newly identified member of the lipase family, plays an important role in high-density lipoprotein metabolism, which catalyzes the hydrolysis of high-density lipoprotein phospholipids and facilitates the clearance of high-density lipoprotein from the circulation. In addition, inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), upregulate endothelial lipase expression, and endothelial lipase also affects the expression of cytokines, which in turn play an important role in atherogenesis. Endothelial lipase expression has been associated with macrophages within human atherosclerotic lesions. However, an important challenge is to determine how endothelial lipase alters the progression of atherosclerosis. Although few data are available from human studies, it seems that plasma endothelial lipase levels in individuals with atherosclerosis might be higher than that measured in healthy individuals. Therefore, we believe that endothelial lipase might be a promising marker for atherosclerosis in clinical settings in the future. PMID:20621031

  13. [Prelipid stage of the morphogenesis of atherosclerosis].

    PubMed

    Zota, E G

    1986-01-01

    On the basis of presented data it can be concluded, that in the preclinical stage of atherosclerosis development when macroscopically observable arterial lesions are still undetectable, a complex process of structural-functional changes takes place in the arterial wall. Under modern methods of investigation it was shown that the concept of "pre lipid" stage of atherosclerosis morphogenesis is somewhat conventional. The infiltration of atherogenic lipoproteids in the arterial wall, their modification and interaction with cell elements of vascular wall serve the basis for complex cell reactions directed to adaptation to new conditions and expelling of excessive lipoproteids. The obtained data introduce a new level of knowledge about patho- and morphogenesis of atherosclerosis. PMID:3530202

  14. Leukocyte activation in atherosclerosis: correlation with risk factors

    Microsoft Academic Search

    A. M Elneihoum; P Falke; B Hedblad; F Lindgärde; K Ohlsson

    1997-01-01

    Leukocytes have been implicated in the development of atherosclerotic vascular diseases, and numerous abnormalities of leukocytes in conjunction with atherosclerosis have been reported. The aim of this study of middle-aged asymptomatic subjects with early atherosclerosis was to determine whether a relationship exists between the levels of plasma markers of leukocyte activation, i.e. cytokines and proteases and risk factors for atherosclerosis

  15. Self-eating in the plaque: what macrophage autophagy reveals about atherosclerosis.

    PubMed

    Sergin, Ismail; Razani, Babak

    2014-05-01

    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 are 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 these 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

  16. Insulin resistance, metabolic stress, and atherosclerosis

    PubMed Central

    Pansuria, Meghana; Xi, Hang; Li, Le; Yang, Xiao-Feng; Wang, Hong

    2012-01-01

    Atherosclerosis, a pathological process that underlies the development of cardiovascular disease, is the primary cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). T2DM is characterized by hyperglycemia and insulin resistance (IR), in which target tissues fail to respond to insulin. Systemic IR is associated with impaired insulin signaling in the metabolic tissues and vasculature. Insulin receptor is highly expressed in the liver, muscle, pancreas, and adipose tissue. It is also expressed in vascular cells. It has been suggested that insulin signaling in vascular cells regulates cell proliferation and vascular function. In this review, we discuss the association between IR, metabolic stress, and atherosclerosis with focus on 1) tissue and cell distribution of insulin receptor and its differential signaling transduction and 2) potential mechanism of insulin signaling impairment and its role in the development of atherosclerosis and vascular function in metabolic disorders including hyperglycemia, hypertension, dyslipidemia, and hyperhomocysteinemia. We propose that insulin signaling impairment is the foremost biochemical mechanism underlying increased cardiovascular morbidity and mortality in atherosclerosis, T2DM, and metabolic syndrome. PMID:22202099

  17. Monocytes in atherosclerosis: subsets and functions

    Microsoft Academic Search

    Frederic Geissmann; Kevin J. Woollard

    2010-01-01

    Chronic inflammation drives atherosclerosis, the leading cause of cardiovascular disease. Over the past two decades, data have emerged showing that immune cells are involved in the pathogenesis of atherosclerotic plaques. The accumulation and continued recruitment of leukocytes are associated with the development of 'vulnerable' plaques. These plaques are prone to rupture, leading to thrombosis, myocardial infarction or stroke, all of

  18. Atherosclerosis: current pathogenesis and therapeutic options

    Microsoft Academic Search

    Heidi Noels; Christian Weber

    2011-01-01

    Coronary artery disease (CAD) arising from atherosclerosis is a leading cause of death and morbidity worldwide. The underlying pathogenesis involves an imbalanced lipid metabolism and a maladaptive immune response entailing a chronic inflammation of the arterial wall. The disturbed equilibrium of lipid accumulation, immune responses and their clearance is shaped by leukocyte trafficking and homeostasis governed by chemokines and their

  19. Interleukins and atherosclerosis: a dysfunctional family grows.

    PubMed

    Spears, Larry D; Razani, Babak; Semenkovich, Clay F

    2013-11-01

    Atherosclerosis is driven by the release of cytokines from macrophages, and the ? isoform of interleukin-1 (IL-1?) is a prime suspect in disease progression. Freigang et al. (2013) now suggest that IL-1?, a close relative, is selectively induced by fatty acids independent of the inflammasome to promote vascular inflammation. PMID:24206661

  20. Interleukins and Atherosclerosis: a Dysfunctional Family Grows

    PubMed Central

    Spears, Larry D.; Razani, Babak; Semenkovich, Clay F.

    2013-01-01

    Atherosclerosis is driven by the release of cytokines from macrophages, and the ? isoform of interleukin 1 (IL-1?) is a prime suspect in disease progression. Freigang et al. (2013) now suggest that IL-1?, a close relative, is selectively induced by fatty acids independent of the inflammasome to promote vascular inflammation. PMID:24206661

  1. 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...

  2. Myeloperoxidase-generated oxidants and atherosclerosis

    Microsoft Academic Search

    Eugene A. Podrez; Husam M. Abu-Soud; Stanley L. Hazen

    2000-01-01

    Atherosclerosis is a chronic inflammatory process where oxidative damage within the artery wall is implicated in the pathogenesis of the disease. Mononuclear phagocytes, an inflammatory cell capable of generating a variety of oxidizing species, are early components of arterial lesions. Their normal functions include host defense and surveillance through regulated generation of diffusible radical species, reactive oxygen or nitrogen species,

  3. Cannabinoids for therapeutic use in atherosclerosis 1

    Microsoft Academic Search

    Sabine Steffens

    2006-01-01

    Summary Atherosclerosis remains the primary cause of heart disease and stroke that causes about 50% of all deaths in Western countries. The identification of promising novel anti-athero- sclerotic therapeutics is therefore of great interest and represents a continued challenge to the medical community. Cannabinoids, such as D9-tetrahydro- cannabinol (THC), the major psychoactive compound of marijuana, their synthetic ana- logs and

  4. Metabolomic analyses for atherosclerosis, diabetes, and obesity

    PubMed Central

    2013-01-01

    Insulin resistance associated with type 2 diabetes mellitus (T2DM), obesity, and atherosclerosis is a global health problem. A portfolio of abnormalities of metabolic and vascular homeostasis accompanies T2DM and obesity, which are believed to conspire to lead to accelerated atherosclerosis and premature death. The complexity of metabolic changes in the diseases presents challenges for a full understanding of the molecular pathways contributing to the development of these diseases. The recent advent of new technologies in this area termed “Metabolomics” may aid in comprehensive metabolic analysis of these diseases. Therefore, metabolomics has been extensively applied to the metabolites of T2DM, obesity, and atherosclerosis not only for the assessment of disease development and prognosis, but also for the biomarker discovery of disease diagnosis. Herein, we summarize the recent applications of metabolomics technology and the generated datasets in the metabolic profiling of these diseases, in particular, the applications of these technologies to these diseases at the cellular, animal models, and human disease levels. In addition, we also extensively discuss the mechanisms linking the metabolic profiling in insulin resistance, T2DM, obesity, and atherosclerosis, with a particular emphasis on potential roles of increased production of reactive oxygen species (ROS) and mitochondria dysfunctions. PMID:24252331

  5. Transgenic rabbits as models for atherosclerosis research

    Microsoft Academic Search

    Margaret E. Brousseau; Jeffrey M. Hoeg

    Several characteristics of the rabbit make it an excellent model for the study of lipoprotein metabolism and atherosclerosis. New Zealand White (NZW) rabbits have low plasma total cholesterol concentrations, high cho- lesteryl ester transfer protein activity, low hepatic lipase (HL) activity, and lack an analogue of human apolipopro- tein (apo) A-II, providing a unique system in which to assess the

  6. Inflammation, Atherosclerosis, and Coronary Artery Disease

    Microsoft Academic Search

    Göran K. Hansson

    2005-01-01

    ecent research has shown that inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Immune cells dominate early atherosclerotic lesions, their effector molecules accelerate progression of the lesions, and activation of inflammation can elicit acute coronary syndromes. This review highlights the role of inflammation in the pathogen- esis of atherosclerotic CAD. It will recount

  7. Chronic Uremia Stimulates LDL Carbamylation and Atherosclerosis

    PubMed Central

    Ray, Debarti; Savenka, Alena V.; Shah, Sudhir V.; Basnakian, Alexei G.

    2010-01-01

    Carbamylated LDL (cLDL) is a potential atherogenic factor in chronic kidney disease (CKD). However, whether elevated plasma cLDL associates with atherosclerosis in vivo is unknown. Here, we induced CKD surgically in apolipoprotein E–deficient (ApoE?/?) mice fed a high-fat diet to promote the development of atherosclerosis. These mice had two- to threefold higher plasma levels of both oxidized LDL (oxLDL) and cLDL compared with control mice. Oral administration of urea increased cLDL approximately eightfold in ApoE?/? mice subjected to unilateral nephrectomy and a high-fat diet, but oxLDL did not rise. Regardless of the model, the uremic mice with high plasma cLDL had more severe atherosclerosis as measured by intravital ultrasound echography and en face aortic staining of lipid deposits. Furthermore, cLDL accumulated in the aortic wall and colocalized with ICAM-1 and macrophage infiltration. In summary, these data demonstrate that elevated plasma cLDL may represent an independent risk factor for uremia-induced atherosclerosis. PMID:20947625

  8. Mutations of mitochondrial genome in carotid atherosclerosis

    PubMed Central

    Sazonova, Margarita A.; Zhelankin, Andrey V.; Barinova, Valeria A.; Sinyov, Vasily V.; Khasanova, Zukhra B.; Postnov, Anton Y.; Orekhov, Alexander N.; Bobryshev, Yuri V.; Sobenin, Igor A.

    2015-01-01

    With aim of detection the spectrum of mitochondrial DNA mutations in patients with carotid atherosclerosis from Moscow Region, we used a Roche 454 high-throughput sequencing of the whole mitochondrial genome. We have found that the presence of a number of homoplasmic mitochondrial DNA mutations in genes of 16S ribosomal RNA, subunits 2, 4, and 5 NADH dehydrogenase, subunits 1 and 2 cytochrome C oxidase, subunit 6 ATP-synthase, tRNA- Leu 2 and cytochrome B differed between conventionally healthy participants of the study and patients with carotid atherosclerosis. We also found heteroplasmic mutations, including insertions one or several nucleotides, that occurred more frequently in mitochondrial DNA of conventionally healthy participants of the study or patients with atherosclerotic lesions. PMID:25852749

  9. Coronary atherosclerosis: Significance of autophagic armour

    PubMed Central

    Arora, Mansi; Kaul, Deepak

    2012-01-01

    Autophagy is a lysosomal degradation pathway of cellular components such as organelles and long-lived proteins. Though a protective role for autophagy has been established in various patho-physiologic conditions such as cancer, neurodegeneration, aging and heart failure, a growing body of evidence now reveals a protective role for autophagy in atherosclerosis, mainly by removing oxidatively damaged organelles and proteins and also by promoting cholesterol egress from the lipid-laden cells. Recent studies by Razani et al and Liao et al unravel novel pathways that might be involved in autophagic protection and in this commentary we highlight the importance of autophagy in atherosclerosis in the light of these two recent papers. PMID:23024838

  10. Innate immune system cells in atherosclerosis.

    PubMed

    Chávez-Sánchez, Luis; Espinosa-Luna, Jose E; Chávez-Rueda, Karina; Legorreta-Haquet, María V; Montoya-Díaz, Eduardo; Blanco-Favela, Francisco

    2014-01-01

    Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by innate and adaptive immune system involvement. A key component of atherosclerotic plaque inflammation is the persistence of different innate immune cell types including mast cells, neutrophils, natural killer cells, monocytes, macrophages and dendritic cells. Several endogenous signals such as oxidized low-density lipoproteins, and exogenous signals such as lipopolysaccharides, trigger the activation of these cells. In particular, these signals orchestrate the early and late inflammatory responses through the secretion of pro-inflammatory cytokines and contribute to plaque evolution through the formation of foam cells, among other events. In this review we discuss how innate immune system cells affect atherosclerosis pathogenesis. PMID:24326322

  11. 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

  12. Emerging, noninvasive surrogate markers of atherosclerosis

    Microsoft Academic Search

    Samir N. Patel; Venkataraman Rajaram; Sanjay Pandya; Benjamin M. Fiedler; Charlotte J. Bai; Rachel Neems; Matt Feinstein; Marshall Goldin; Steven B. Feinstein

    2004-01-01

    Noninvasive surrogate markers of atherosclerosis allow the physician to identify subclinical disease before the occurrence\\u000a of adverse cardiovascular events, thereby limiting the need to perform invasive diagnostic procedures. Imaging modalities,\\u000a such as carotid artery ultrasound, two-dimensional echocardiography, coronary artery calcium imaging, cardiac magnetic resonance\\u000a imaging, ankle-brachial indices, brachial artery reactivity testing, and epicardial coronary flow reserve measurements, provide\\u000a information that

  13. Cyclooxygenase2 and inflammation in atherosclerosis

    Microsoft Academic Search

    MacRae F Linton; Sergio Fazio

    2004-01-01

    By regulating the production of eicosanoids, cyclooxygenase (COX) modulates processes contributing to atherosclerosis and thrombosis, including platelet aggregation and the local inflammatory response. COX-2, a key mediator of inflammation, is upregulated in activated monocyte\\/macrophages, suggesting that COX-2 inhibition might reduce atherogenesis through its anti-inflammatory effects. In mouse models, selective inhibition of COX-2 or its deletion in macrophages protects against early

  14. [Enterosorbents in the treatment of atherosclerosis].

    PubMed

    Piskun, R P; Pentiuk, A A; Serkova, V K; Polesia, T L; Savitskaia, E A

    1998-01-01

    The article lists, characterizes, and discusses the mechanism of the action of endosorbents possessing hypocholesteremic and hypolipidemic effects. Among them are natural endosorbents--food fibers (cellulose, hemicellulose, pectins, gum, mucus, lignin and chitin compounds, etc.); artificial specific affinin and nonspecific carbonic enterosorbents (carbonitrate family, granulated, fibrous), as well as silica (aerosil, polysorb). The effectiveness and pathogenetic expediency of correcting disorders of lipid metabolism in atherosclerosis with enterosorbents is substantiated. PMID:9621181

  15. ?-Defensin: Link between inflammation and atherosclerosis

    Microsoft Academic Search

    Hisham Nassar; Ehud Lavi; Sa’ed Akkawi; Khalil Bdeir; Samuel N. Heyman; P. N. Raghunath; John Tomaszewski; Abd Al-Roof Higazi

    2007-01-01

    BackgroundSeveral markers of inflammation predict the risk of thrombotic cardiovascular events in patients with atherosclerosis. However, the mechanism by which vascular inflammation promotes atherothrombotic disease is incompletely understood. Human neutrophil peptides 1–3, also known as ?-defensins, are found in human atherosclerotic arteries, inhibit LDL metabolism and fibrinolysis and promote Lp(a) binding. We asked, therefore, if ?-defensins are risk factors for

  16. Pathophysiology of atherosclerosis: Development, regression, restenosis

    Microsoft Academic Search

    Mark R. Adams; Scott Kinlay; Gavin J. Blake; James L. Orford; Peter Ganz; Andrew P. Selwyn

    2000-01-01

    There is now a very large number of patients with coronary artery disease who have also undergone percutaneous interventions\\u000a such as coronary angioplasty. Atherosclerosis and restenosis are two distinct pathologic processes with different underlying\\u000a pathophysiologic mechanisms, different natural histories, different clinical presentations, and treatment strategies. Management\\u000a strategies to target both processes are currently poorly applied in clinical practice. The development

  17. [Mitogen-activated protein kinases in atherosclerosis].

    PubMed

    Bryk, Dorota; Olejarz, Wioletta; Zapolska-Downar, Danuta

    2014-01-01

    Intracellular signalling cascades, in which MAPK (mitogen-activated protein kinases) intermediate, are responsible for a biological response of a cell to an external stimulus. MAP kinases, which include ERK1/2 (extracellular signalling-regulated kinase), JNK (c-Jun N-terminal kinase) and p 38 MAPK, regulate the activity of many proteins, enzymes and transcription factors and thus have a wide spectrum of biological effects. Many basic scientific studies have defined numerous details of their pathway organization and activation. There are also more and more studies suggesting that individual MAP kinases probably play an important role in the pathogenesis of atherosclerosis. They may mediate inflammatory processes, endothelial cell activation, monocyte/macrophage recruitment and activation, smooth muscle cell proliferation and T-lymphocyte differentiation, all of which represent crucial mechanisms involved in pathogenesis of atherosclerosis. The specific inhibition of an activity of the respective MAP kinases may prove a new therapeutic approach to attenuate atherosclerotic plaque formation in the future. In this paper, we review the current state of knowledge concerning MAP kinase-dependent cellular and molecular mechanisms underlying atherosclerosis. PMID:24491891

  18. Increased atherosclerosis in myeloperoxidase-deficient mice

    PubMed Central

    Brennan, Marie-Luise; Anderson, Melissa M.; Shih, Diana M.; Qu, Xiao-Dan; Wang, Xuping; Mehta, Asha C.; Lim, Lesley L.; Shi, Weibin; Hazen, Stanley L.; Jacob, Jason S.; Crowley, Jan R.; Heinecke, Jay W.; Lusis, Aldons J.

    2001-01-01

    Myeloperoxidase (MPO), a heme enzyme secreted by activated phagocytes, generates an array of oxidants proposed to play critical roles in host defense and local tissue damage. Both MPO and its reaction products are present in human atherosclerotic plaque, and it has been proposed that MPO oxidatively modifies targets in the artery wall. We have now generated MPO-deficient mice, and show here that neutrophils from homozygous mutants lack peroxidase and chlorination activity in vitro and fail to generate chlorotyrosine or to kill Candida albicans in vivo. To examine the potential role of MPO in atherosclerosis, we subjected LDL receptor–deficient mice to lethal irradiation, repopulated their marrow with MPO-deficient or wild-type cells, and provided them a high-fat, high-cholesterol diet for 14 weeks. White cell counts and plasma lipoprotein profiles were similar between the two groups at sacrifice. Cross-sectional analysis of the aorta indicated that lesions in MPO-deficient mice were about 50% larger than controls. Similar results were obtained in a genetic cross with LDL receptor–deficient mice. In contrast to advanced human atherosclerotic lesions, the chlorotyrosine content of aortic lesions from wild-type as well as MPO-deficient mice was essentially undetectable. These data suggest an unexpected, protective role for MPO-generated reactive intermediates in murine atherosclerosis. They also identify an important distinction between murine and human atherosclerosis with regard to the potential involvement of MPO in protein oxidation. PMID:11181641

  19. [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

  20. Experimental models investigating the inflammatory basis of atherosclerosis

    Microsoft Academic Search

    Ahmed Soliman; Patrick Kee

    2008-01-01

    Inflammation is considered an important aspect in the development of atherosclerosis. Genetic manipulations of animal models\\u000a susceptible to atherosclerosis have unraveled the contribution of various inflammatory pathways implicated in the development\\u000a of atherosclerosis. These inflammatory pathways not only lead to the recruitment and entry of inflammatory cells into the\\u000a arterial wall, they also modify the morphology and composition of atherosclerotic

  1. Relationship between leukocyte count and angiographical characteristics of coronary atherosclerosis

    Microsoft Academic Search

    En-zhi Jia; Zhi-jian Yang; Biao Yuan; Xiao-ling Zang; Rong-hu Wang; Tie-bing Zhu; Lian-sheng Wang; Bo Chen; Wen-zhu Ma

    2005-01-01

    Aim:To explore the relationship between differential leucocyte count and coronary atherosclerosis.Methods:The study population consisted of 507 consecutive patients (376 male and 131 female) who underwent coronary angiography for suspected or known coronary atherosclerosis. The patients' smoking and drinking habits were investigated, and anthropometric measurements, serum measurements, and hematological measurements were conducted for every patient. The severity of coronary atherosclerosis was

  2. 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

  3. Beyond the joint: Subclinical atherosclerosis in rheumatoid arthritis

    PubMed Central

    Scarno, Antongiulio; Perrotta, Fabio Massimo; Cardini, Francesca; Carboni, Alessia; Annibali, Gianmarco; Lubrano, Ennio; Spadaro, Antonio

    2014-01-01

    Rheumatoid arthritis is a chronic autoimmune inflammatory disease associated with increased cardiovascular risk and higher mortality in respect to general population. Beyond joint disease, inflammation is the major determinant of accelerated atherosclerosis observed in rheumatoid arthritis. We review the relationship between inflammation, atherosclerosis and cardiovascular risk in rheumatoid arthritis, focusing on the assessment of subclinical atherosclerosis by functional and morphological methods. These tools include flow mediated dilatation, carotid intima-media thickness, ankle/brachial index, coronary calcium content, pulse wave analysis and serum biomarker of subclinical atherosclerosis. PMID:25035836

  4. Fire Suppression

    Microsoft Academic Search

    C. Presser; J. C. Yang

    \\u000a Water sprinkler sprays (with relatively large droplet sizes) in residential and commercial structures are probably the most\\u000a well-known application of sprays in fire suppression. In more recent years, water mists (characterized by reduced droplet\\u000a sizes, which may contain additives) have been considered as a replacement for Halon 1301, the most common fire suppressant\\u000a chemical aboard aircraft and ships, but banned

  5. 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

  6. The Metabolic Syndrome, LDL Particle Size, and Atherosclerosis The Atherosclerosis and Insulin Resistance (AIR) Study

    Microsoft Academic Search

    Johannes Hulthe; Lena Bokemark; John Wikstrand; Bjorn Fagerberg

    An operative definition of the metabolic syndrome has been suggested by a working group associated with the World Health Organization in 1998. The aim of this study was to examine whether small, low density lipoprotein (LDL) particle size was associated with the metabolic syndrome and with subclinical atherosclerosis as measured by ultrasound in the carotid and femoral arteries. The study

  7. Impact of Prediabetic Status on Coronary Atherosclerosis

    PubMed Central

    Kurihara, Osamu; Takano, Masamichi; Yamamoto, Masanori; Shirakabe, Akihiro; Kimata, Nakahisa; Inami, Toru; Kobayashi, Nobuaki; Munakata, Ryo; Murakami, Daisuke; Inami, Shigenobu; Okamatsu, Kentaro; Ohba, Takayoshi; Ibuki, Chikao; Hata, Noritake; Seino, Yoshihiko; Mizuno, Kyoichi

    2013-01-01

    OBJECTIVE To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity. RESEARCH DESIGN AND METHODS Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups. RESULTS Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ?2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09–55.6], P = 0.005; and OR 4.13 [95% CI 1.01–17.0], P = 0.049, respectively). CONCLUSIONS Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself. PMID:23223344

  8. Lipid homeostasis in macrophages - implications for atherosclerosis.

    PubMed

    Schmitz, G; Grandl, M

    2008-01-01

    In industrialized societies with excess food supply, obesity is an expanding problem. As a result of metabolic overload, besides obesity, insulin resistance, type-2 diabetes, dyslipidemia, hypertension, and atherosclerosis develop, which together make up the metabolic syndrome. The imbalance of lipid uptake, metabolism, and removal in many organs such as the liver, muscle, adipose tissue, vessel wall, and macrophages triggers organ transdifferentiation toward lipid storage phenotypes. Macrophages, foam cells, and osteoclasts in calcifying lesions are a hallmark of atherosclerosis and the metabolic syndrome, and must be regarded as an important therapeutic target. In this review, pathways regulating lipid homeostasis in macrophages are updated. These include lipid influx through different receptor entry pathways, the role of membrane microdomains, endolysosomal and cytosolic lipid storage leading to phospholipidosis, and lipid droplet accumulation or activation of lipid efflux either through the Golgi system or bypassing this organelle on the way to the plasma membrane. The interdependence of these pathways and pharmacological modifications are described. The monocyte innate immunity receptor complex in defining monocyte subpopulations and their role in cardiovascular disease is taken into account. The composition of certain molecular lipid species in membrane microdomains and other organelles is essential for cellular functions affecting raft dynamics, signal transduction, and membrane and organelle trafficking. It is very likely that the underlying defects in lipid-associated rare genetic diseases such as ABCA1 deficiency, Niemann-Pick disease type C, as well as the more frequent complex disorders associated with atherosclerosis and phospholipidosis are related to disturbances in membrane homeostasis, signal transduction, and cellular lipid metabolism. PMID:18425439

  9. Internal Carotid Artery Stenting for Intracranial Atherosclerosis

    PubMed Central

    Osbun, Joshua W.; Kim, Louis J.

    2014-01-01

    Intracranial atherosclerotic disease is a significant cause of stroke in the United States. Much like coronary atherosclerosis, this disease leads to arterial stenosis secondary to the buildup of lipid-based plaques in intracranial vessels. Ischemic stroke may occur following thromboembolic events near the site of stenosis or from watershed ischemia secondary to cerebral hypoperfusion. While this disease has been treated with intracranial angioplasty and stenting and cerebrovascular bypass surgery, the current literature supports aggressive medical management with dual antiplatelet therapy, treatment of comorbidities such as hypertension, diabetes, and hyperlipidemia, and lifestyle modification. Intracranial angioplasty and stenting is reserved for cases of medical failure. PMID:25624980

  10. Susceptibility to Spontaneous Atherosclerosis in Pigeons: An Autosomal Recessive Trait

    Microsoft Academic Search

    S. C. Smith; E. C. Smith; R. L. Taylor

    2001-01-01

    The inheritance pattern for susceptibility to spontaneous (noninduced) aortic athero- sclerosis in pigeons was determined by crossbreeding and backcrossing experi- ments with atherosclerosis-susceptible White Carneau and atherosclerosis-resis- tant Show Racer breeds. Susceptibility, assessed by the presence of grossly visi- ble lesions at the celiac bifurcation of the aorta at 3 years of age, demonstrated an inheritance pattern consistent with an

  11. Endothelial therapy of atherosclerosis and its risk factors

    Microsoft Academic Search

    T. Traupe; J. Ortmann; K. Munter; M. Barton

    2003-01-01

    Atherosclerosis is a chronic systemic disease of the vasculature with an inflammatory component. It accounts for the majority of cardiovascular morbidity and mortality in industrialized countries and its incidence is increasing in developing countries. The impairment of vascular endothelial cell function in atherosclerosis and in conditions associated with increased cardiovascular risk is an important determinant of disease progression. The reduction

  12. Photoangioplasty: new applications of photodynamic therapy in atherosclerosis

    NASA Astrophysics Data System (ADS)

    Rockson, Stanley G.

    2000-05-01

    Atherosclerosis has traditionally held appeal as a pathologic entity in which photodynamic therapy might arrest or reverse the manifestations of disease. Earlier attempts to bring photodynamic therapy to the human clinical arena were hampered by the limitations of the photosensitizers under investigation, including the propensity to phototoxic manifestations and light-induced trauma to surrounding, normal vascular tissues. Many of these inherent limitations may be circumvented by newer photosensitizers that are activated at longer, more optimal wavelengths of light energy. Advances in fiberoptic catheter design for the endovascular delivery of light have also contributed to the greater applicability of photodynamic therapy to human atherosclerosis. Initial experiences with one family of photosensitizers, the texaphyrins, indicate that photodynamic therapy of human peripheral arterial atherosclerosis is feasible, safe, and well-tolerated. Photodynamic therapy of atherosclerosis holds promise for the treatment of de novo atherosclerosis and may have future applicability in the treatment, and perhaps prevention, of restenosis.

  13. [Key laboratory diagnostic biomarkers of coronary atherosclerosis].

    PubMed

    Ragino, Iu I; Cherniavski?, A M; Eremenko, N V; Shakhtshne?der, E V; Polonskaia, Ia V; Tsymbal, S Iu; Ivanova, M V; Voevoda, M I

    2011-01-01

    Laboratory lipid and lipoprotein biomarkers (total cholesterol - CH, triglycerides - TG, low-density and high-density lipoprotein cholesterol- LDL-CH, HDL-CH, apolipoproteins B and A1 - apoB, apoA1), carbohydrate biomarkers (plasma glucose, basal insulin), high sensitive C-reactive protein (hsCRP) and oxidative biomarkers (basal level of lipid peroxidation [LPO] products in LDL, LDL resistance to oxidation in vitro, oxidative modification of apoLDL and level of LDL lipophilic antioxidants) were studied in 388 men aged 42-70 years: 96 citizens of Western Siberia with angiographically documented coronary atherosclerosis and coronary heart disease (CHD); 292 men of population sample of citizens of Novosibirsk, including 44 men with CHD confirmed by standardized criteria and methods. Significant associations were found of coronary atherosclerosis and CHD with laboratory diagnostic biomarkers like blood levels of HDL-CH, TG, apoB, apoA1, basal insulin, hsCRP and basal level of LPO products in LDL and LDL resistance to oxidation. PMID:21627612

  14. Mechanisms that regulate macrophage burden in atherosclerosis

    PubMed Central

    Randolph, Gwendalyn J.

    2014-01-01

    Mononuclear phagocytes (MPs) relevant to atherosclerosis include monocytes, macrophages, and dendritic cells (DCs). A decade ago, studies on macrophage behavior in atherosclerotic lesions were often limited to quantification of total macrophage area in cross-sections of plaques. While technological advances are still needed to examine plaque MP populations in an increasingly dynamic and informative manner, innovative methods to interrogate the biology of MPs in atherosclerotic plaques developed in the last few years point to a number of mechanisms that regulate the accumulation and function of MPs within plaques. Here, I review the evolution of atherosclerotic plaques with respect to changes in the MP compartment from the initiation of plaque to its progression and regression, discussing the roles that recruitment, proliferation, and retention of MPs play at these different disease stages. Additional work in the future will be needed to better distinguish macrophages and DCs in plaque and to address some basic unknowns in the field, including just how cholesterol drives accumulation of macrophages in lesions to build plaques in the first place and how macrophages as major effectors of innate immunity work together with components of the adaptive immune response to drive atherosclerosis. Answers to these questions are sought with the goal in mind of reversing disease where it exists and preventing its development where it does not. PMID:24855200

  15. Quantum dot mediated imaging of atherosclerosis

    NASA Astrophysics Data System (ADS)

    Jayagopal, Ashwath; Su, Yan Ru; Blakemore, John L.; Linton, MacRae F.; Fazio, Sergio; Haselton, Frederick R.

    2009-04-01

    The progression of atherosclerosis is associated with leukocyte infiltration within lesions. We describe a technique for the ex vivo imaging of cellular recruitment in atherogenesis which utilizes quantum dots (QD) to color-code different cell types within lesion areas. Spectrally distinct QD were coated with the cell-penetrating peptide maurocalcine to fluorescently-label immunomagnetically isolated monocyte/macrophages and T lymphocytes. QD-maurocalcine bioconjugates labeled both cell types with a high efficiency, preserved cell viability, and did not perturb native leukocyte function in cytokine release and endothelial adhesion assays. QD-labeled monocyte/macrophages and T lymphocytes were reinfused in an ApoE-/- mouse model of atherosclerosis and age-matched controls and tracked for up to four weeks to investigate the incorporation of cells within aortic lesion areas, as determined by oil red O (ORO) and immunofluorescence ex vivo staining. QD-labeled cells were visible in atherosclerotic plaques within two days of injection, and the two cell types colocalized within areas of subsequent ORO staining. Our method for tracking leukocytes in lesions enables high signal-to-noise ratio imaging of multiple cell types and biomarkers simultaneously within the same specimen. It also has great utility in studies aimed at investigating the role of distinct circulating leukocyte subsets in plaque development and progression.

  16. Histopathologic Evaluation of Basilar Artery Atherosclerosis

    PubMed Central

    Labadzhyan, Artak; Csiba, Laszlo; Narula, Navneet; Zhou, Jun; Narula, Jagat; Fisher, Mark

    2011-01-01

    Introduction There has been limited attention to pathological features of basilar artery atherosclerosis. It has been assumed that pathology of basilar artery atherosclerosis mimics that of other vascular beds. Methods To define the nature of the basilar artery atherosclerotic lesions we analyzed postmortem intracranial artery samples from eight subjects with history of stroke. Results Atherosclerotic lesions were present in 7/8 arteries examined, with a mean estimated stenosis of 34%. Lumen thrombus with a disrupted fibrous cap was seen in 1 lesion; the remaining 6 lesions revealed a thick fibrous cap. Neovascularity and calcification were seen in 1 lesion and mild to moderate inflammation was seen in 3 lesions. Necrotic core was present in 4/7 lesions, and was associated with plaque rupture in the only disrupted lesion. Conclusions Basilar artery atherosclerotic lesions were relatively benign in this series of patients presenting with stroke. While confirmation is needed with larger sample size, the relative paucity of neovascularity suggests a possibly distinctive histopathological profile. PMID:21624622

  17. Insulin and atherosclerosis: how are they related?

    PubMed

    Monnier, L; Hanefeld, M; Schnell, O; Colette, C; Owens, D

    2013-04-01

    The relationship between insulin and atherosclerosis is complex. People with type 2 diabetes are affected by three main glycaemic disorders: chronic hyperglycaemia; glycaemic variability; and iatrogenic hypoglycaemia. In addition to this triumvirate, the diabetic condition is characterized by lipid disorders, chronic low-grade inflammation and activation of oxidative stress. All these associated disorders reflect the insulin-resistant nature of type 2 diabetes and contribute to the development and progression of cardiovascular (CV) diseases. By both lowering plasma glucose and improving the lipid profile, insulin exerts beneficial effects on CV outcomes. In addition, insulin has several pleiotropic effects such as anti-inflammatory, antithrombotic and antioxidant properties. Insulin per se exerts an inhibitory effect on the activation of oxidative stress and seems able to counteract the pro-oxidant effects of ambient hyperglycaemia and glycaemic variability. However, insulin actions remain a subject of debate with respect to the risk of adverse CV events, which can increase in individuals exposed to high insulin doses. Evidence from the large-scale, long-term ORIGIN trial suggests that early implementation of insulin supplementation therapy in the course of glycaemic disorders, including type 2 diabetes, has a neutral impact on CV outcomes compared with standard management. Thus, the answer to the question "What impact does insulin have on atherosclerosis?" remains unclear, even though it is logical to deduce that insulin should be initiated as soon as possible and that small doses of insulin early on are better than higher doses later in the disease process. PMID:23507269

  18. Periodontitis as a Risk Factor of Atherosclerosis

    PubMed Central

    Bartova, Jirina; Sommerova, Pavla; Lyuya-Mi, Yelena; Mysak, Jaroslav; Janatova, Tatjana; Podzimek, Stepan

    2014-01-01

    Over the last two decades, the amount of evidence corroborating an association between dental plaque bacteria and coronary diseases that develop as a result of atherosclerosis has increased. These findings have brought a new aspect to the etiology of the disease. There are several mechanisms by which dental plaque bacteria may initiate or worsen atherosclerotic processes: activation of innate immunity, bacteremia related to dental treatment, and direct involvement of mediators activated by dental plaque and involvement of cytokines and heat shock proteins from dental plaque bacteria. There are common predisposing factors which influence both periodontitis and atherosclerosis. Both diseases can be initiated in early childhood, although the first symptoms may not appear until adulthood. The formation of lipid stripes has been reported in 10-year-old children and the increased prevalence of obesity in children and adolescents is a risk factor contributing to lipid stripes development. Endothelium damage caused by the formation of lipid stripes in early childhood may lead to bacteria penetrating into blood circulation after oral cavity procedures for children as well as for patients with aggressive and chronic periodontitis. PMID:24741613

  19. Ginseng Extracts Restore High-Glucose Induced Vascular Dysfunctions by Altering Triglyceride Metabolism and Downregulation of Atherosclerosis-Related Genes

    PubMed Central

    Chan, Gabriel Hoi-huen; Law, Betty Yuen-kwan; Chu, John Man-tak; Yue, Kevin Kin-man; Jiang, Zhi-hong; Lau, Chi-wai; Huang, Yu; Chan, Shun-wan; Ying-kit Yue, Patrick; Wong, Ricky Ngok-shun

    2013-01-01

    The king of herbs, Panax ginseng, has been used widely as a therapeutic agent vis-à-vis its active pharmacological and physiological effects. Based on Chinese pharmacopeia Ben Cao Gang Mu and various pieces of literature, Panax ginseng was believed to exert active vascular protective effects through its antiobesity and anti-inflammation properties. We investigated the vascular protective effects of ginseng by administrating ginseng extracts to rats after the induction of diabetes. We found that Panax ginseng can restore diabetes-induced impaired vasorelaxation and can reduce serum triglyceride but not cholesterol level in the diabetic rats. The ginseng extracts also suppressed the expression of atherosclerosis-related genes and altered the expression of lipid-related genes. The results provide evidence that Panax ginseng improves vascular dysfunction induced by diabetes and the protective effects may possibly be due to the downregulation of atherosclerosis-related genes and altered lipid metabolism, which help to restore normal endothelium functions. PMID:24194784

  20. P2X7R is involved in the progression of atherosclerosis by promoting NLRP3 inflammasome activation

    PubMed Central

    PENG, KUANG; LIU, LUSHAN; WEI, DANGHENG; LV, YUNCHENG; WANG, GANG; XIONG, WENHAO; WANG, XIAOQING; ALTAF, AFRASYAB; WANG, LILI; HE, DAN; WANG, HONGYAN; QU, PENG

    2015-01-01

    Purinergic 2X7 receptor (P2X7R) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) are expressed in macrophages in atherosclerotic lesions. However, the mechanisms through which P2X7R participates in the inflammatory response in atherosclerosis remain largely unknown. The aim of the present study was to investigate the role of P2X7R in atherosclerosis and the mechanisms of action of the NLRP3 inflammasome following stimulation with oxidized low-density lipoprotein (oxLDL). We observed the expression and distribution of P2X7R in the atherosclerotic plaque in the coronary arteries from an autopsy specimen and in that of the aortic sinuses of apoE?/? mice by immunohistochemistry and immunofluorescence staining. The specificity of short interfering RNA (siRNA) was used to suppress P2X7R and NLRP3 mRNA expression. RT-qPCR and western blot analysis were used to analyze mRNA and protein expression, respectively. Co-immunoprecipitation was used to examine the interaction between protein kinase R (PKR) phosphorylation and NLRP3. P2X7R and NLRP3 were expressed at high levels in the atherosclerotic plaque in the coronary arteries. Stimulation with oxLDL upregulated P2X7R, NLRP3 and interleukin (IL)-1? expression. P2X7R knockdown by siRNA suppressed NLRP3 inflammasome activation by inhibiting the PKR phosphorylation mediated by oxLDL. In the atherosclerotic lesions in the aortic sinuses of apoE?/? mice, P2X7R expression was found at high levels. Moreover, P2X7R siRNA attenuated the development of atherosclerosis in the apoE?/? mice. In conclusion, our results demonstrate that P2X7R plays a significant role in the development of atherosclerosis and regulates NLRP3 inflammasome activation by promoting PKR phosphorylation. PMID:25761252

  1. Association of plasma lipid levels with atherosclerosis prevalence in psittaciformes.

    PubMed

    Beaufrère, Hugues; Vet, Dr Med; Cray, Carolyn; Ammersbach, Mélanie; Tully, Thomas N

    2014-09-01

    The prevalence of atherosclerosis is high in the captive psittacine population and increases with age and female sex. The genera Psittacus, Amazona, and Nymphicus are predisposed to atherosclerosis, whereas the genera Cacatua and Ara are less susceptible. Plasma cholesterol and lipoprotein abnormalities have been suggested as risk factors in the development of atherosclerosis as observed in mammals. To investigate whether the psittacine genera susceptibility to atherosclerosis and the known risk factors of age and sex could be associated with differences in the lipid profile, a retrospective analysis was conducted on blood lipid values from 5625 birds. Prevalence values were obtained from a previously published, large, case-control study and were compared with identified trends in plasma lipid profiles. Genus-specific differences were identified in plasma total cholesterol values that corresponded to observed trends in the prevalence of clinically important atherosclerotic lesions, which were also highly correlated. The effect of age was significant but was mild and may not account for the dramatic increase in atherosclerosis prevalence observed with age. In addition, Quaker parrots ( Myiopsitta monachus ), which were used as experimental models for psittacine atherosclerosis and dyslipidemia, were found to have the highest values in all lipid profile parameters. The results of this study suggest that the differences observed in prevalence among species of the psittacine genera may partly be explained by differences in plasma total cholesterol levels. Results also support the use of Quaker parrots as models for studying atherosclerosis and dyslipidemia. PMID:25843322

  2. Accelerated coronary atherosclerosis and H syndrome

    PubMed Central

    Shankarappa, Ravindranath K; Ananthakrishna, Rajiv; Math, Ravi S; Yalagudri, Sachin Dhareppa; Karur, Satish; Dwarakaprasad, Ramesh; Nanjappa, Manjunath C; Molho-Pessach, Vered

    2011-01-01

    A 12-year-old boy with insulin dependent diabetes mellitus, presented with acute myocardial infarction. Intracoronary thrombolysis with urokinase restored TIMI III flow in the culprit vessel. After stabilisation with medical therapy, unusual clinical findings in the form of cutaneous hyperpigmentation and hypertrichosis, affecting the lower extremities, were appreciated. These and other phenotypic features were consistent with H syndrome, a recently described autosomal recessive genodermatosis, and confirmed by mutation analysis. Despite being on optimal medical therapy for coronary artery disease, the patient presented 3 months thereafter, with unstable angina which was successfully managed with percutaneous coronary intervention. An unusual occurrence of coronary artery disease with accelerated atherosclerosis in a child with H syndrome is presented herein. Identification of further patients with this novel disorder will clarify the possible association, suggested here, with increased risk for coronary or other vascular events. PMID:22679148

  3. Sustained arterial injury and progression of atherosclerosis.

    PubMed

    Sueishi, K; Yasunaga, C; Castellanos, E; Kumamoto, M; Tanaka, K

    1990-01-01

    In this paper the following findings were described: 1) Murine arteriosclerosis induced by immune challenge was ultrastructurally characterized by intimal monocyte-macrophage recruitment and minor endothelial alterations; 2) Atherosclerotic lesions of human coronary arteries exhibited frequently segmental or patchy neovascularization, probably representing a response to intimal injury as an example of repair process. Newly formed blood vessels in the intima were derived from both adventitial and luminal endothelial growth; 3) Angiogenesis in vitro was related to the activation of fibrinolytic system especially via the autocrine production of u-PA from endothelial cells, and this process was modulated by cytokines and TGF beta. These findings add more evidence for the hypothesis that the chronic inflammation-repair process plays an essential role in the initiation and progression of atherosclerosis. PMID:1701074

  4. Chemokines: established and novel targets in atherosclerosis

    PubMed Central

    Koenen, Rory R; Weber, Christian

    2011-01-01

    In their role as small chemotactic cytokines, chemokines are crucial mediators and regulators of leukocyte trafficking during immune surveillance and inflammation. Their involvement in the development and progression of inflammatory diseases has been subject of intense investigation. Concordantly, the chemokine system has been explored in search for therapeutic targets to prevent or treat inflammatory disorders, such as atherosclerosis. Targeting the chemokine system offers various entry points for a causative treatment of this widespread and chronic illness. Although this approach has encountered some setbacks, several innovative compounds are currently in an advanced stage of development. In this review, the current standing of this dynamic field is highlighted and the potential advantages and drawbacks of particular strategies are discussed. PMID:22038924

  5. Effects and mechanisms of icariin on atherosclerosis

    PubMed Central

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

    2015-01-01

    Purpose: Icariin, a flavonoid isolated from the traditional Chinese herbal medicine Epimedium brevicornum Maxim, has been shown to process anti-inflammatory, antioxidative actions and anti-atherosclerosis activity in vivo and in vitro. The purpose of this study was to investigate the effects and mechanisms of icariin on atherosclerosis by human umbilical vein endothelial cells (HUVECs). Methods: The effects of icariin on the activity of HUVECs induced by oxidized low-density lipoprotein (ox-LDL) were detected by MTT assay. Then we studied the effects of icariin on the adhesion of monocyte with HUVECs induced by ox-LDL. The secretion of E-selectin, intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) by HUVECs were measured by enzyme-linked immunosorbent assay (ELISA) method. Finally the mRNA levels of ICAM-1, VCAM-1, E-selectin of HUVECs were analyzed by real time RT-PCR. Results: MTT result indicated that icariin (10, 20, 40 ?mol/L) could inhibit HUVECs injury induced by ox-LDL in a concentration-dependent manner (P < 0.05). The adhesion of monocyte with HUVECs induced by ox-LDL was inhibited by icariin in a concentration-dependent manner (P < 0.05). The levels of ICAM-1, VCAM-1, E-selectin of icariin groups were significantly decreased in a concentration-dependent manner compared with ox-LDL-simulated group (P < 0.05). The mRNA expressions of ICAM-1, VCAM-1, E-selectin of icariin groups were also downregulated significantly compared with ox-LDL-simulated group (P < 0.05). Conclusions: Icariin can prevent atherosclerotic lesion. Its mechanism may be that it can defend against the oxidation damage to HUVECs, inhibit the adhesion of monocyte to HUVECs, and reduce the secretion and expression of adhesion molecules including ICAM-1, VCAM-1, E-selectin.

  6. Inflammatory and Autoimmune Reactions in Atherosclerosis and Vaccine Design Informatics

    PubMed Central

    Jan, Michael; Meng, Shu; Chen, Natalie C.; Mai, Jietang; Wang, Hong; Yang, Xiao-Feng

    2010-01-01

    Atherosclerosis is the leading pathological contributor to cardiovascular morbidity and mortality worldwide. As its complex pathogenesis has been gradually unwoven, the regime of treatments and therapies has increased with still much ground to cover. Active research in the past decade has attempted to develop antiatherosclerosis vaccines with some positive results. Nevertheless, it remains to develop a vaccine against atherosclerosis with high affinity, specificity, efficiency, and minimal undesirable pathology. In this review, we explore vaccine development against atherosclerosis by interpolating a number of novel findings in the fields of vascular biology, immunology, and bioinformatics. With recent technological breakthroughs, vaccine development affords precision in specifying the nature of the desired immune response—useful when addressing a disease as complex as atherosclerosis with a manifold of inflammatory and autoimmune components. Moreover, our exploration of available bioinformatic tools for epitope-based vaccine design provides a method to avoid expenditure of excess time or resources. PMID:20414374

  7. 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 ...

  8. Mechanics of Atherosclerosis, Hypertension Induced Growth, and Arterial Remodeling 

    E-print Network

    Hayenga, Heather Naomi

    2012-07-16

    In order to create informed predictive models that capture artery dependent responses during atherosclerosis progression and the long term response to hypertension, one needs to know the structural, biochemical and mechanical ...

  9. Mechanics of Atherosclerosis, Hypertension Induced Growth, and Arterial Remodeling

    E-print Network

    Hayenga, Heather Naomi

    2012-07-16

    In order to create informed predictive models that capture artery dependent responses during atherosclerosis progression and the long term response to hypertension, one needs to know the structural, biochemical and mechanical properties as a...

  10. Oxidized low density lipoprotein, stem cells, and atherosclerosis

    PubMed Central

    2012-01-01

    Oxidized low density lipoprotein (ox-LDL), a risk factor of atherosclerosis, facilitates the formation and vulnerability of atherosclerotic plaque, thus contributing to several clinical complications. Stem cells participate in vascular repair after damage and atherosclerosis is a process of inflammation accompanied with vascular injury. Researchers have proposed that stem cells participate in the formation of atherosclerotic plaque. Also, because ox-LDL is capable of inducing toxic effects on stem cells, it is reasonable to postulate that ox-LDL promotes the progress of atherosclerosis via acting on stem cells. In the present article, we review the relationship between ox-LDL, stem cells, and atherosclerosis and a portion of the associated mechanisms. PMID:22747902

  11. OxLDL-pulsed dendritic cells: an immunotherapy in atherosclerosis

    Microsoft Academic Search

    Kim Habets; Gijs van Puijvelde; Leonie van Duivenvoorde; Eva van Wanrooij; Paula de Vos; Jan Willem; Cohen Tervaert; Theo van Berkel

    Abstract Background. Modification of lipoproteins plays an important role in the development,of atherosclerosis. Oxidatively modified low-density lipoprotein (oxLDL) has a number of pro-inflammatory effects, whereas immunization,with various forms of oxLDL is able to reduce,atherosclerosis. The uptake of modified LDL by dendritic cells (DCs) and the presentation of epitopes thereof may form an important step in the immunomodulatoryeffects of LDL. In

  12. Prevention and Treatment of Atherosclerosis: A Practitioner's Guide for 2008

    Microsoft Academic Search

    Sandra J. Lewis

    2009-01-01

    Atherosclerosis causes nearly 75% of cardiovascular-related deaths and is found in 80% to 90% of adults ?30 years old in the United States. Successful treatment minimizes lifetime chances of cardiovascular events, morbidity, and mortality. Risk factors for atherosclerosis should be monitored, beginning in childhood, even in asymptomatic patients. Modifiable factors (e.g., blood pressure, smoking, serum lipids) and nonmodifiable factors (e.g.,

  13. Cytokine network and T cell immunity in atherosclerosis

    Microsoft Academic Search

    Hafid Ait-Oufella; Soraya Taleb; Ziad Mallat; Alain Tedgui

    2009-01-01

    Atherosclerosis is a chronic inflammatory disease of the arterial wall where both innate and adaptive immune responses contribute\\u000a to disease initiation and progression. Recent studies established that subtypes of T cells, regulatory T cells (Tregs), actively\\u000a involved in the maintenance of immunological tolerance, inhibit the development and progression of atherosclerosis. Here,\\u000a we review the current knowledge on the Treg response

  14. Advanced Glycation End Product Interventions Reduce Diabetes-Accelerated Atherosclerosis

    Microsoft Academic Search

    Josephine M. Forbes; Louis Teo; Loon Yee; Vicki Thallas; Markus Lassila; Riccardo Candido; Karin A. Jandeleit-Dahm; Merlin C. Thomas; Wendy C. Burns; Elizabeth K. Deemer; Susan M. Thorpe; Mark E. Cooper; Terri J. Allen

    2004-01-01

    Advanced glycation end product (AGE) formation may contribute to the progression of atherosclerosis, particularly in diabetes. The present study explored atherosclerosis in streptozotocin-induced diabetic apo- lipoprotein E- deficient (apoE\\/) mice that were ran- domized (n 20) to receive for 20 weeks no treatment, the AGE cross-link breaker ALT-711, or the inhibitor of AGE formation aminoguanidine (AG). A sixfold in- crease

  15. Genetic markers of oxidative stress and coronary atherosclerosis

    Microsoft Academic Search

    Nageswara R. Madamanchi; Igor Tchivilev; Marschall S. Runge

    2006-01-01

    Atherosclerosis, the primary cause of coronary artery disease (CAD), is a multifactorial disease, the molecular etiology of\\u000a which involves interaction of many genes and environmental factors. Reactive oxygen species are integral to many cellular\\u000a and biomolecular processes that are active in the transition of incipient fatty streaks into acute coronary syndromes. Animal\\u000a models of atherosclerosis and correlative data from human

  16. Effect of Clarithromycin on Inflammatory Markers in Patients with Atherosclerosis

    Microsoft Academic Search

    Hans F. Berg; Boulos Maraha; Gert-Jan Scheffer; Marcel F. Peeters; Jan A. J. W. Kluytmans

    2003-01-01

    Atherosclerosis can to a certain extent be regarded as an inflammatory disease. Also, inflammatory markers may provide information about cardiovascular risk. Whether macrolide antibiotics, especially clarithromycin, have an anti-inflammatory effect in patients with atherosclerosis is not exactly known. To study this phenom- enon, a placebo-controlled, randomized, double-blind study was performed. A total of 231 patients with documented coronary artery disease

  17. Cholesterol and hematopoietic stem cells: inflammatory mediators of atherosclerosis.

    PubMed

    Lang, Jennifer K; Cimato, Thomas R

    2014-05-01

    Atherosclerosis causing heart attack and stroke is the leading cause of death in the modern world. Therapy for end-stage atherosclerotic disease using CD34(+) hematopoietic cells has shown promise in human clinical trials, and the in vivo function of hematopoietic and progenitor cells in atherogenesis is becoming apparent. Inflammation plays a central role in the pathogenesis of atherosclerosis. Cholesterol is a modifiable risk factor in atherosclerosis, but in many patients cholesterol levels are only mildly elevated. Those with high cholesterol levels often have elevated circulating monocyte and neutrophil counts. How cholesterol affects inflammatory cell levels was not well understood. Recent findings have provided new insight into the interaction among hematopoietic stem cells, cholesterol, and atherosclerosis. In mice, high cholesterol levels or inactivation of cholesterol efflux transporters have multiple effects on hematopoietic stem cells (HSPCs), including promoting their mobilization into the bloodstream, increasing proliferation, and differentiating HSPCs to the inflammatory monocytes and neutrophils that participate in atherosclerosis. Increased levels of interleukin-23 (IL-23) stimulate IL-17 production, resulting in granulocyte colony-stimulating factor (G-CSF) secretion, which subsequently leads to HSPC release into the bloodstream. Collectively, these findings clearly link elevated cholesterol levels to increased circulating HSPC levels and differentiation to inflammatory cells that participate in atherosclerosis. Seminal questions remain to be answered to understand how cholesterol affects HSPC-mobilizing cytokines and the role they play in atherosclerosis. Translation of findings in animal models to human subjects may include HSPCs as new targets for therapy to prevent or regress atherosclerosis in patients. PMID:24646491

  18. 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

  19. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

    PubMed Central

    Koeth, Robert A.; Wang, Zeneng; Levison, Bruce S.; Buffa, Jennifer A.; Org, Elin; Sheehy, Brendan T.; Britt, Earl B.; Fu, Xiaoming; Wu, Yuping; Li, Lin; Smith, Jonathan D.; DiDonato, Joseph A.; Chen, Jun; Li, Hongzhe; Wu, Gary D.; Lewis, James D.; Warrier, Manya; Brown, J. Mark; Krauss, Ronald M.; Tang, W. H. Wilson; Bushman, Frederic D.; Lusis, Aldons J.; Hazen, Stanley L.

    2013-01-01

    Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk. PMID:23563705

  20. A major role for RCAN1 in atherosclerosis progression

    PubMed Central

    Méndez-Barbero, Nerea; Esteban, Vanesa; Villahoz, Silvia; Escolano, Amelia; Urso, Katia; Alfranca, Arantzazu; Rodríguez, Cristina; Sánchez, Susana A; Osawa, Tsuyoshi; Andrés, Vicente; Martínez-González, José; Minami, Takashi; Redondo, Juan Miguel; Campanero, Miguel R

    2013-01-01

    Atherosclerosis is a complex inflammatory disease involving extensive vascular vessel remodelling and migration of vascular cells. As RCAN1 is implicated in cell migration, we investigated its contribution to atherosclerosis. We show RCAN1 induction in atherosclerotic human and mouse tissues. Rcan1 was expressed in lesional macrophages, endothelial cells and vascular smooth muscle cells and was induced by treatment of these cells with oxidized LDLs (oxLDLs). Rcan1 regulates CD36 expression and its genetic inactivation reduced atherosclerosis extension and severity in Apoe?/? mice. This effect was mechanistically linked to diminished oxLDL uptake, resistance to oxLDL-mediated inhibition of macrophage migration and increased lesional IL-10 and mannose receptor expression. Moreover, Apoe?/?Rcan1?/? macrophages expressed higher-than-Apoe?/? levels of anti-inflammatory markers. We previously showed that Rcan1 mediates aneurysm development and that its expression is not required in haematopoietic cells for this process. However, transplantation of Apoe?/?Rcan1?/? bone-marrow (BM) cells into Apoe?/? recipients confers atherosclerosis resistance. Our data define a major role for haematopoietic Rcan1 in atherosclerosis and suggest that therapies aimed at inhibiting RCAN1 expression or function might significantly reduce atherosclerosis burden. PMID:24127415

  1. Aortic Atherosclerosis in Systemic Lupus Erythematosus

    PubMed Central

    Roldan, Paola C; Ratliff, Michelle; Snider, Richard; Macias, Leonardo; Rodriguez, Rodrigo; Sibbitt, Wilmer; Roldan, Carlos A.

    2014-01-01

    Aortic atherosclerosis (AoA) defined as intima-media thickening or plaques and aortic stiffness (AoS) also considered an atherosclerotic process and defined as decreased vessel distensibility (higher pulse pressure to achieve similar degree of vessel distension) are common in patients with SLE. Immune-mediated inflammation, thrombogenesis, traditional atherogenic factors, and therapy-related metabolic abnormalities are the main pathogenic factors of AoA and AoS. Pathology of AoA and AoS suggests an initial subclinical endothelialitis or vasculitis, which is exacerbated by thrombogenesis and atherogenic factors and ultimately resulting in AoA and AoS. Computed tomography (CT) for detection of arterial wall calcifications and arterial tonometry for detection of increased arterial pulse wave velocity are the most common diagnostic methods for detecting AoA and AoS, respectively. MRI may become a more applicable and accurate technique than CT. Although transesophageal echocardiography accurately detects earlier and advanced stages of AoA and AoS, it is semi-invasive and cannot be used as a screening method. Although imaging techniques demonstrate highly variable prevalence rates, on average about one third of adult SLE patients may have AoA or AoS. Age at SLE diagnosis; SLE duration; activity and damage; corticosteroid therapy; metabolic syndrome; chronic kidney disease; and mitral annular calcification are common independent predictors of AoA and AoS. Also, AoA and AoS are highly associated with carotid and coronary atherosclerosis. Earlier stages of AoA and AoS are usually subclinical. However, earlier stages of disease may be causally related or contribute to peripheral or cerebral embolism, pre-hypertension and hypertension, and increased left ventricular afterload resulting in left ventricular hypertrophy and diastolic dysfunction. Later stages of disease predisposes to visceral ischemia, aortic aneurysms and aortic dissection. Even earlier stages of AoA and AoS have been associated with increased cardiovascular and cerebrovascular morbidity and mortality of SLE patients. Aggressive non-steroidal immunosuppressive therapy and non-pharmacologic and pharmacologic interventions for control of atherogenic risk factors may prevent the development or progression of AoA and AoS and may decrease cardiovascular and cerebrovascular morbidity and mortality in SLE. PMID:25593786

  2. Prevention of hypercholesterolemia and atherosclerosis in the hyperlipidemia and atherosclerosis-prone Japanese (LAP) quail by taurine supplementation

    Microsoft Academic Search

    Shigeru Murakami; T. Sakurai; H. Tomoike; M. Sakono; T. Nasu; N. Fukuda

    2010-01-01

    The effects of taurine supplementation on the serum cholesterol levels and the progression of atherosclerosis were investigated\\u000a in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail. The ingestion of a high-cholesterol diet containing\\u000a 1% cholesterol by LAP quails for 60 days resulted in a marked elevation in serum non-HDL cholesterol and triglyceride, as\\u000a well as severe aortic lesions with lipid droplets. An

  3. 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

  4. Diverse Roles of Macrophages in Atherosclerosis: From Inflammatory Biology to Biomarker Discovery

    PubMed Central

    Gui, Ting; Shimokado, Aiko; Sun, Yujing; Akasaka, Takashi; Muragaki, Yasuteru

    2012-01-01

    Cardiovascular disease, a leading cause of mortality in developed countries, is mainly caused by atherosclerosis, a chronic inflammatory disease. Macrophages, which differentiate from monocytes that are recruited from the blood, account for the majority of leukocytes in atherosclerotic plaques. Apoptosis and the suppressed clearance of apoptotic macrophages (efferocytosis) are associated with vulnerable plaques that are prone to rupture, leading to thrombosis. Based on the central functions of macrophages in atherogenesis, cytokines, chemokines, enzymes, or microRNAs related to or produced by macrophages have become important clinical prognostic or diagnostic biomarkers. This paper discusses the impact of monocyte-derived macrophages in early atherogenesis and advanced disease. The role and possible future development of macrophage inflammatory biomarkers are also described. PMID:22577254

  5. 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.

  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)

    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.

  7. Atherosclerosis: from biology to pharmacological treatment

    PubMed Central

    Riccioni, Graziano; Sblendorio, Valeriana

    2012-01-01

    A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter, and is pleiotropic since it affects blood pressure, lipid profiles, glucose metabolism, inflammation, and atherothrombotic disease progression. Given the current obstacles, success of primary prevention remains uncertain. At the same time, the consequences of delay and inaction will inevitably be disastrous, and the sense of urgency mounts. Pathological and epidemiological data confirm that atherosclerosis begins in early childhood, and advances seamlessly and inexorably throughout life. Risk factors in childhood are similar to those in adults, and track between stages of life. When indicated, aggressive treatment should begin at the earliest indication, and be continued for many years. For those patients at intermediate risk according to global risk scores, C-reactive protein, coronary artery calcium, and carotid intima-media thickness are available for further stratification. Using statins for primary prevention is recommended by guidelines, is prevalent, but remains under prescribed. Statin drugs are unrivaled, evidence-based, major weapons to lower cardiovascular risk. Even when low density lipoprotein cholesterol targets are attained, over half of patients continue to have disease progression and clinical events. Though clinical evidence is incomplete, altering or raising the blood high density lipoprotein cholesterol level continues to be pursued. The aim of this review is to point out the attention of key aspects of vulnerable plaques regarding their pathogenesis and treatment. PMID:23097661

  8. Coronary atherosclerosis in noncardiac deaths: An autopsy study

    PubMed Central

    Vyas, Priti; Gonsai, Ratigar Narangar; Meenakshi, Charu; Nanavati, Meeta G.

    2015-01-01

    Introduction: Atherosclerosis leading to ischemic heart disease (IHD) is the most common cause of cardiac deaths worldwide. To evaluate the prevalence of atherosclerosis, an autopsy-based study conducted on subjects who died of noncardiac causes can be a valuable tool. With this hypothesis, we conducted this study on the hearts of subjects who died of noncardiac causes. Materials and Methods: This study was conducted from August 2012 to February 2013 at Department of Pathology, BJ Medical College, Ahmedabad, Gujarat. The deceased patients who died of noncardiac causes and underwent autopsy at our hospital, their hearts were sent to our department for histopathological analysis. The hearts were fixed in 10% formalin, weighed, measured, and the three main coronary arteries were dissected out and carefully examined for any histological evidence of atherosclerotic plaques and associated pathological lesions and graded according to the classification given by American Heart Association. Results: A total of 250 autopsy cases were evaluated. Amongst them 113 were deaths due to noncardiac causes, of which 83 (73.45%) subjects had evidence of atherosclerosis. In the study, 68 (82%) were males and 15 (18%) were females. Left anterior descending artery (LADA; 69%) was the most commonly involved coronary artery. Triple vessel disease was found in 22% of subjects. Conclusion: The study showed alarmingly high prevalence of atherosclerosis. The pathogenesis of coronary atherosclerosis begins at a younger age in Indian population. Though the incidence of atherosclerosis is more common in males compared to females; coronary atherosclerosis is an important risk factor for IHDs in both sexes and screening for the same should begin at an early age. PMID:25861201

  9. Naoxintong protects against atherosclerosis through lipid-lowering and inhibiting maturation of dendritic cells in LDL receptor knockout mice fed a high-fat diet.

    PubMed

    Zhao, Jingjing; Zhu, Hong; Wang, Shijun; Ma, Xin; Liu, Xiangwei; Wang, Cong; Zhao, Hangtian; Fan, Shuxia; Jin, Xueting; Zhao, Buchang; Zhao, Tao; Jia, Lifu; Wang, Keqiang; Zou, Yunzeng; Hu, Kai; Sun, Aijun; Ge, Junbo

    2013-01-01

    Naoxintong (NXT), a Chinese Materia Medica standardized product, extracted from 16 various kinds of Chinese traditional herbal medicines including Salvia miltiorrhiza, Angelica sinennsis, Astragali Radix, is clinically effective in treating atherosclerosisrelated diseases. Here, we tested the hypothesis that the anti-atherosclerosis effects of NXT might be mediated by suppressing maturation of dendritic cells (DCs) in a mice model of atherosclerosis. LDLR(-/-) mice fed a high-fat diet were treated with placebo, NXT (0.7 g/kg/d, oral diet) or simvastatin (100mg/kg/d, oral diet) for 8 weeks, respectively. NXT treatment significantly reduced plasma triglyceride (112 ± 18 mg/dl vs. 192 ± 68 mg/dl, P<0.05) and total cholesterol (944 ± 158 mg/dl vs. 1387 ± 208 mg/dl, P<0.05) compared to placebo treatment. Vascular lesions were significantly smaller and macrophage content and amount of DCs in plaques were significantly less in NXT and simvastatin groups than in placebo group (all P<0.05). In addition, expressions of splenic DC membrane molecules (CD40, CD86 and CD80) and the plasma level of IL-12p70 were significantly lower in NXT and simvastatin groups than in placebo group. In conclusion, NXT protects against atherosclerosis through lipid-lowering and inhibiting DCs maturation in this mice model of atherosclerosis. PMID:23438960

  10. G Protein-coupled Estrogen Receptor Protects from Atherosclerosis

    PubMed Central

    Meyer, Matthias R.; Fredette, Natalie C.; Howard, Tamara A.; Hu, Chelin; Ramesh, Chinnasamy; Daniel, Christoph; Amann, Kerstin; Arterburn, Jeffrey B.; Barton, Matthias; Prossnitz, Eric R.

    2014-01-01

    Coronary atherosclerosis and myocardial infarction in postmenopausal women have been linked to inflammation and reduced nitric oxide (NO) formation. Natural estrogen exerts protective effects on both processes, yet also displays uterotrophic activity. Here, we used genetic and pharmacologic approaches to investigate the role of the G protein-coupled estrogen receptor (GPER) in atherosclerosis. In ovary-intact mice, deletion of gper increased atherosclerosis progression, total and LDL cholesterol levels and inflammation while reducing vascular NO bioactivity, effects that were in some cases aggravated by surgical menopause. In human endothelial cells, GPER was expressed on intracellular membranes and mediated eNOS activation and NO formation, partially accounting for estrogen-mediated effects. Chronic treatment with G-1, a synthetic, highly selective small molecule agonist of GPER, reduced postmenopausal atherosclerosis and inflammation without uterotrophic effects. In summary, this study reveals an atheroprotective function of GPER and introduces selective GPER activation as a novel therapeutic approach to inhibit postmenopausal atherosclerosis and inflammation in the absence of uterotrophic activity. PMID:25532911

  11. Role of mast cells in atherosclerosis: a classical inflammatory disease.

    PubMed

    Spinas, E; Kritas, S K; Saggini, A; Mobili, A; Caraffa, A; Antinolfi, P; Pantalone, A; Tei, M; Speziali, A; Saggini, R; Conti, P

    2014-01-01

    Atherosclerosis is an inflammatory disease and hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Variance in plasma LDL cholesterol concentration may be associated with differences in cardiovascular disease risk and high levels of lipids are associated with increased risk of developing atherosclerosis. Macrophages, which generate pro-inflammatory cytokines, mainly interleukin-1 (IL-1) and tumor necrosis factor-? (TNF-alpha), are deeply involved in atherosclerosis, as well as mast cells which generate several cytokines, including IL-6 and IFN-gamma, and chemokines such as eotaxin, MCP-1 and RANTES involved in monocyte recruitment and differentiation in the arterial wall. In addition, mast cells participate in lipid retention and vascular cell remodeling, and are mediators of innate and adaptive immunity during atherosclerosis. Mast cells which accumulate in the human arterial intima and adventitia during atherosclerotic plaque progression, release vasoactive and angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid metabolites, histamine, cytokines/chemokines, platelet activating factor (PAF) and proteolytic enzymes. Mast cells can be activated by pro-inflammatory stimuli, including cytokines, hypercholesterolemia, and hyperglycemia, and trigger the endothelial expression of adhesion molecules such as P-selection, vascular cell adhesion molecule-1 (VCAM-1) and chemokines which mediate the recruitment and adhesion of leukocytes. The participation of mast cells in atherosclerosis is still an enigma and it may be of therapeutic interest to clarify this process. PMID:25572731

  12. Ambulatory Hypercholesterolemia Management in Patients with Atherosclerosis

    PubMed Central

    Persell, Stephen D; Maviglia, Saverio M; Bates, David W; Ayanian, John Z

    2005-01-01

    OBJECTIVE To determine whether outpatient cholesterol management varies by gender or race among patients with atherosclerosis, and assess factors related to subsequent cholesterol control. DESIGN Retrospective cohort study. SETTING Primary care clinics affiliated with an academic medical center. PARTICIPANTS Two hundred forty-three patients with coronary heart disease, cerebrovascular disease, or peripheral vascular disease and low-density lipoprotein cholesterol (LDL-C)>130 mg/dl. MEASUREMENTS AND MAIN RESULTS The primary process of care assessed for 1,082 office visits was cholesterol management (medication intensification or LDL-C monitoring). Cholesterol management occurred at 31.2% of women's and 38.5% of men's visits (P =.01), and 37.3% of black and 31.7% of white patients' visits (P =.09). Independent predictors of cholesterol management included female gender (adjusted risk ratio [ARR], 0.77; 95% confidence interval [CI], 0.60 to 0.97), seeing a primary care clinician other than the patient's primary care physician (ARR, 0.23; 95% CI, 0.11 to 0.45), and having a new clinical problem addressed (ARR, 0.60; 95% CI, 0.48 to 0.74). After 1 year, LDL-C <130 mg/dl occurred less often for women than men (41% vs 61%; P =.003), black than white patients (39% vs 58%; P =.01), and patients with only Medicare insurance than with commercial insurance (37% vs 58%; P =.008). Adjustment for clinical characteristics and management attenuated the relationship between achieving an LDL-C <130 mg/dl and gender. CONCLUSIONS In this high-risk population with uncontrolled cholesterol, cholesterol management was less intensive for women than men but similar for black and white patients. Less intense cholesterol management accounted for some of the disparity in cholesterol control between women and men but not between black and white patients. PMID:15836544

  13. Cell-derived microparticles in atherosclerosis: biomarkers and targets for pharmacological modulation?

    E-print Network

    Paris-Sud XI, Université de

    Cell-derived microparticles in atherosclerosis: biomarkers and targets for pharmacological, the pathophysiological properties of MPs may contribute to atherosclerosis development. In addition, pharmacological com in thrombosis · Pharmacological modulation of plasma MP concentrations - Statins - Anti-oxidants - Peroxisome

  14. 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...

  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. Relative contributions of age and atherosclerosis to vascular stiffness.

    PubMed

    Santelices, Linda C; Rutman, Sarah J; Prantil-Baun, Rachelle; Vorp, David A; Ahearn, Joseph M

    2008-05-01

    To determine the relative contributions of aging and atherosclerosis to vascular stiffness, we studied aortic stiffness, plaque, and elastin in 8-, 16-, 25-, and 34-week-old male ApoE-KO and C57BL/6J control mice (N = 48). Stiffness increased gradually in both strains up to 25 weeks (p < 0.05), and dramatically between 25 and 34 weeks in ApoE-KO (p < 0.001). Aging ApoE-KO demonstrated increased plaque (p = 0.02), medial thickening (p < 0.001), and severe elastin fragmentation (p < 0.001). We conclude that the contribution of aging to vascular stiffness is relatively minor compared with the influence of atherosclerosis. However, the effect of atherosclerosis on stiffness is significant only with advanced stages of plaque formation. PMID:20443820

  17. Molecular pathways regulating macrophage polarization: implications for atherosclerosis.

    PubMed

    Hoeksema, Marten A; Stöger, J Lauran; de Winther, Menno P J

    2012-06-01

    Recent years have seen a tremendous development of our insight into the biology of atherosclerosis and its acute thrombotic manifestations. Inflammation now takes center stage among traditional risk factors as a decisive factor in cardiovascular risk. Consequently, its assessment and modulation have become key to clinical care and fundamental research alike. Plaque macrophages orchestrate many of the inflammatory processes that occur throughout atherogenesis. These cells are characteristically heterogeneous and adopt diverse activation states in response to micro-environmental triggers. In this review, macrophage-mediated inflammation in atherosclerosis sets the scene for a discussion of the gene regulatory mechanisms that facilitate and shape polarized macrophage phenotypes. When applicable, we consider these factors within the context of atherosclerosis and reflect on opportunities for future application. PMID:22407286

  18. Role of Helicobacter pylori infection in pathogenesis of atherosclerosis

    PubMed Central

    Vijayvergiya, Rajesh; Vadivelu, Ramalingam

    2015-01-01

    Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect. PMID:25810813

  19. Adipokines as a novel link between obesity and atherosclerosis

    PubMed Central

    Yoo, Hye Jin; Choi, Kyung Mook

    2014-01-01

    The traditional perception of adipose tissue as a storage organ of fatty acids has been replaced by the notion that adipose tissue is an active endocrine organ, releasing various adipokines that are involved in the pathogenesis of obesity-related metabolic disturbances. Obesity is a well-known risk factor for atherosclerosis, and accelerates atherosclerosis by many mechanisms such as increase in blood pressure and glucose level, abnormal lipid profiles, and systemic inflammation. Furthermore, growing evidence suggests that some adipokines directly mediate the process of atherosclerosis by influencing the function of endothelial cells, arterial smooth muscle cells, and macrophages in vessel walls. In obese patients, the secretion and coordination of such adipokines is abnormal, and the secretion of specific adipokines increases or decreases. Accordingly, the discovery of new adipokines and elucidation of their functions might lead to a new treatment strategy for metabolic disorders related to obesity, including cardiovascular diseases. PMID:24936256

  20. Regulation of IL-17 in atherosclerosis and related autoimmunity.

    PubMed

    Ryu, Heeju; Chung, Yeonseok

    2015-08-01

    Patients with systemic autoimmune diseases exhibit a higher incidence of atherosclerosis. Conversely, hyperlipidemia has been known to accelerate autoimmune diseases in humans as well as in experimental animal. How atherosclerosis impacts autoimmunity remains poorly understood. Importantly, recent studies showed that several pro-atherogenic factors including cholesterol, oxidized low-density lipoprotein and fatty acids regulate the production of IL-17 and IL-17-promoting cytokines from innate and adaptive immune cells. Given that IL-17 is associated with a number of autoimmune diseases in humans, dissecting the mechanisms beyond the mutual regulation of pro-atherogenic factors and IL-17 might provide a novel pathophysiology between atherosclerosis and autoimmune diseases. In this review, we discuss our current understanding related to the role of pro-atherogenic factors in IL-17 production and autoimmune diseases. PMID:25890878

  1. The Influence of Innate and Adaptive Immune Responses on Atherosclerosis

    PubMed Central

    Witztum, Joseph L.; Lichtman, Andrew H.

    2014-01-01

    Both the chronic development of atherosclerotic lesions and the acute changes in lesion phenotype that lead to clinical cardiovascular events are significantly influenced by the innate and adaptive immune responses to lipoprotein deposition and oxidation in the arterial wall. The rapid pace of discovery of mechanisms of immunologic recognition, effector functions, and regulation has significantly influenced the study of atherosclerosis, and our new knowledge is beginning to affect how we treat this ubiquitous disease. In this review, we discuss recent advances in our understanding of how innate and adaptive immunity contribute to atherosclerosis, as well as therapeutic opportunities that arise from this knowledge. PMID:23937439

  2. Characterization of Platelet Gamma Glutamyltransferase and Its Alteration in Cases of Atherosclerosis

    Microsoft Academic Search

    Turay Yardimci; Azize Yaman; Orhan Ulutin

    1995-01-01

    Among the various functional and biochemical alterations in the platelets of cases of atherosclerosis, the membrane alterations occupy an important place. The platelet intrinsic membrane protein gamma glutamyltransferase (GGT), which is involved in glutathione metabolism, has shown decreased activity in cases of atherosclerosis. To add new insights into the pathogenesis of atherosclerosis, GGT is characterized and correlated with other alterations.

  3. Promotion of Vascular Smooth Muscle Cell Growth by Homocysteine: A Link to Atherosclerosis

    Microsoft Academic Search

    Jer-Chia Tsai; Mark A. Perrella; Masao Yashizumi; Chung-Ming Hsieh; Edgar Haber; Robert Schlegel; Mu-En Lee

    1994-01-01

    Plasma homocysteine levels are elevated in 20-30% of all patients with premature atherosclerosis. Although elevated homocysteine levels have been recognized as an independent risk factor for myocardial infarction and stroke, the mechanism by which these elevated levels cause atherosclerosis is unknown. To understand the role of homocysteine in the pathogenesis of atherosclerosis, we examined the effect of homocysteine on the

  4. Correlations between peripheral differential leukocyte counts and carotid atherosclerosis in non-smokers

    Microsoft Academic Search

    Zei-Shung Huang; Jiann-Shing Jeng; Chiu-Hwa Wang; Ping-Keung Yip; Tzy-Haw Wu; Ti-Kai Lee

    2001-01-01

    Substantial evidence clearly indicates the immuno-inflammatory nature of atherosclerosis and the important roles of monocytes and other leukocytes in atherogenesis. The relationship between atherosclerosis and the peripheral monocyte count, however, has been equivocal and uncertain so far. One possible reason may be an opposing effect of different major risk factors of atherosclerosis on the monocyte count, e.g. smoking increases the

  5. 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

  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. Changes in transcriptome of macrophages in atherosclerosis.

    PubMed

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

    2015-06-01

    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

  8. Heme oxygenase-1, oxidation, inflammation, and atherosclerosis.

    PubMed

    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

  9. IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic dysfunction in a mouse model of lupus-associated atherosclerosis.

    PubMed

    Watkins, Amanda A; Yasuda, Kei; Wilson, Gabriella E; Aprahamian, Tamar; Xie, Yao; Maganto-Garcia, Elena; Shukla, Prachi; Oberlander, Lillian; Laskow, Bari; Menn-Josephy, Hanni; Wu, Yuanyuan; Duffau, Pierre; Fried, Susan K; Lichtman, Andrew H; Bonegio, Ramon G; Rifkin, Ian R

    2015-02-15

    Premature atherosclerosis is a severe complication of lupus and other systemic autoimmune disorders. Gain-of-function polymorphisms in IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing lupus, and IRF5 deficiency in lupus mouse models ameliorates disease. However, whether IRF5 deficiency also protects against atherosclerosis development in lupus is not known. In this study, we addressed this question using the gld.apoE(-/-) mouse model. IRF5 deficiency markedly reduced lupus disease severity. Unexpectedly, despite the reduction in systemic immune activation, IRF5-deficient mice developed increased atherosclerosis and also exhibited metabolic dysregulation characterized by hyperlipidemia, increased adiposity, and insulin resistance. Levels of the atheroprotective cytokine IL-10 were reduced in aortae of IRF5-deficient mice, and in vitro studies demonstrated that IRF5 is required for IL-10 production downstream of TLR7 and TLR9 signaling in multiple immune cell types. Chimera studies showed that IRF5 deficiency in bone marrow-derived cells prevents lupus development and contributes in part to the increased atherosclerosis. Notably, IRF5 deficiency in non-bone marrow-derived cells also contributes to the increased atherosclerosis through the generation of hyperlipidemia and increased adiposity. Together, our results reveal a protective role for IRF5 in lupus-associated atherosclerosis that is mediated through the effects of IRF5 in both immune and nonimmune cells. These findings have implications for the proposed targeting of IRF5 in the treatment of autoimmune disease as global IRF5 inhibition may exacerbate cardiovascular disease in these patients. PMID:25595782

  10. Vitamin E suppresses isoprostane generation in vivo and reduces atherosclerosis in ApoE-deficient mice

    Microsoft Academic Search

    Domenico Praticò; Rajendra K. Tangirala; Daniel J. Rader; Joshua Rokach; Garret A. FitzGerald

    1998-01-01

    Oxidative modification of low density lipoprotein (LDL) has been implicated in atherogenesis. Evidence consistent with this hypothesis includes the presence of oxidized lipids in atherosclerotic lesions, the newly discovered biological properties conferred on LDL by oxidation and the acceleration of atherogenesis by in vivo delivery of the gene for 15-lipoxygenase, an oxidizing enzyme present in atherosclerotic lesions. However, it is

  11. Atherosclerosis in chronic kidney disease: the role of macrophages

    Microsoft Academic Search

    Valentina Kon; MacRae F. Linton; Sergio Fazio

    2010-01-01

    Patients with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease and loss of renal parenchyma accelerates atherosclerosis in animal models. Macrophages are central to atherogenesis because they regulate cholesterol traffic and inflammation in the arterial wall. CKD influences macrophage behavior at multiple levels, rendering them proatherogenic. Even at normal creatinine levels, macrophages from uninephrectomized Apoe?\\/? mice

  12. Racial Differences in Thoracic Aorta Atherosclerosis Among Ischemic Stroke Patients

    Microsoft Academic Search

    Vishal Gupta; Navin C. Nanda; Dilek Yesilbursa; Wen Ying Huang; Vijaya Gupta; Qing Li; Camilo R. Gomez

    Background and Purpose—Atherosclerosis of the thoracic aorta is an independent risk factor for stroke. There is little information on the impact of race in the prevalence of thoracic aorta atherosclerotic plaques among ischemic stroke patients. This study was an attempt to objectively assess the prevalence, thickness, and burden of thoracic aorta atherosclerotic plaques in a large population of ischemic stroke

  13. Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies

    Microsoft Academic Search

    Victor J. Dzau; Ruediger C. Braun-Dullaeus; Daniel G. Sedding

    2002-01-01

    In atherosclerosis, the vascular smooth muscle cell (VSMC) contributes to vessel wall inflammation and lipoprotein retention, as well as to the formation of the fibrous cap that provides stability to the plaque. The VSMC can undergo a proliferative response that underlies the development of in-stent restenosis, bypass graft occlusion and transplant vasculopathy. Although the benefit\\/risk of therapeutic inhibition of VSMC

  14. The Role of Oxidative Stress and Autophagy in Atherosclerosis

    PubMed Central

    Perrotta, Ida; Aquila, Saveria

    2015-01-01

    Atherosclerosis is a multifactorial, multistep disorder of large- and medium-sized arteries involving, in addition to age, gender and menopausal status, a complex interplay between lifestyle and genetic risk factors. Atherosclerosis usually begins with the diffusion and retention of atherogenic lipoproteins into the subendothelial space of the artery wall where they become oxidized by local enzymes and accumulate, leading to the formation of a cushion called atheroma or atheromatous or fibrofatty plaque, composed of a mixture of macrophages, lymphocytes, smooth muscle cells (SMCs), cholesterol cleft, necrotic debris, and lipid-laden foam cells. The pathogenesis of atherosclerosis still remains incompletely understood but emerging evidence suggests that it may involve multiple cellular events, including endothelial cell (EC) dysfunction, inflammation, proliferation of vascular SMCs, matrix (ECM) alteration, and neovascularization. Actually, a growing body of evidence indicates that autophagy along with the chronic and acute overproduction of reactive oxygen species (ROS) is integral to the development and progression of the disease and may represent fruitful avenues for biological investigation and for the identification of new therapeutic targets. In this review, we give an overview of ROS and autophagy in atherosclerosis as background to understand their potential role in this vascular disease. PMID:25866599

  15. Anti-inflammatory therapeutics for the treatment of atherosclerosis

    Microsoft Academic Search

    Israel F. Charo; Rebecca Taub

    2011-01-01

    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

  16. Translating molecular discoveries into new therapies for atherosclerosis

    Microsoft Academic Search

    Daniel J. Rader; Alan Daugherty

    2008-01-01

    Atherosclerosis is characterized by the thickening of the arterial wall and is the primary cause of coronary artery disease and cerebrovascular disease, two of the most common causes of illness and death worldwide. Clinical trials have confirmed that certain lipoproteins and the renin-angiotensin-aldosterone system are important in the pathogenesis of atherosclerotic cardiovascular disease, and that interventions targeted towards these are

  17. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development.

    PubMed

    Berbée, Jimmy F P; Boon, Mariëtte R; Khedoe, P Padmini S J; Bartelt, Alexander; Schlein, Christian; Worthmann, Anna; Kooijman, Sander; Hoeke, Geerte; Mol, Isabel M; John, Clara; Jung, Caroline; Vazirpanah, Nadia; Brouwers, Linda P J; Gordts, Philip L S M; Esko, Jeffrey D; Hiemstra, Pieter S; Havekes, Louis M; Scheja, Ludger; Heeren, Joerg; Rensen, Patrick C N

    2015-01-01

    Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by ?3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe(-/-) and Ldlr(-/-) mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe(-/-) and Ldlr(-/-) mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis. PMID:25754609

  18. Obesity and aging: determinants of endothelial cell dysfunction and atherosclerosis

    Microsoft Academic Search

    Matthias Barton

    2010-01-01

    Endothelial cells are both the source and target of factors contributing to atherosclerosis. After the discovery of the endothelium-derived relaxing factor (EDRF) by Robert F. Furchgott in 1980 it soon became clear that endothelial cells also release vasoactive factors distinct from nitric oxide (NO) namely, endothelium-derived contracting factors (EDCF) as well as hyperpolarizing factors (EDHF). Vasoactive factors derived from endothelial

  19. Premature Coronary-Artery Atherosclerosis in Systemic Lupus Erythematosus

    Microsoft Academic Search

    Yu Asanuma; Annette Oeser; Ayumi K. Shintani; Elizabeth Turner; Nancy Olsen; Sergio Fazio; MacRae F. Linton; Paolo Raggi; C. Michael Stein

    2003-01-01

    background Premature coronary artery disease is a major cause of illness and death in patients with systemic lupus erythematosus, but little is known about the prevalence, extent, and caus- es of coronary-artery atherosclerosis. methods We used electron-beam computed tomography to screen for the presence of coronary- artery calcification in 65 patients with systemic lupus erythematosus (mean ( ± SD) age,

  20. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development

    PubMed Central

    Berbée, Jimmy F. P.; Boon, Mariëtte R; Khedoe, P. Padmini S. J.; Bartelt, Alexander; Schlein, Christian; Worthmann, Anna; Kooijman, Sander; Hoeke, Geerte; Mol, Isabel M.; John, Clara; Jung, Caroline; Vazirpanah, Nadia; Brouwers, Linda P.J.; Gordts, Philip L.S.M.; Esko, Jeffrey D.; Hiemstra, Pieter S.; Havekes, Louis M.; Scheja, Ludger; Heeren, Joerg; Rensen, Patrick C.N.

    2015-01-01

    Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by ?3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe?/? and Ldlr?/? mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe?/? and Ldlr?/? mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis. PMID:25754609

  1. Innate and Adaptive Immunity in the Pathogenesis of Atherosclerosis

    Microsoft Academic Search

    Andreas Zeiher; Göran K. Hansson; Peter Libby; Uwe Schönbeck; Zhong-Qun Yan

    2010-01-01

    This review considers critically the evidence for the involvement of mediators of innate and acquired immunity in various stages of atherosclerosis. Rapidly mobilized arms of innate immunity, including phagocytic leukocytes, complement, and proinflammatory cytokines, contribute to atherogenesis. In addition, adaptive immunity, with its T cells, antibodies, and immunoregulatory cytokines, powerfully modulates disease activity and progression. Atherogen- esis involves cross talk

  2. Blood Flow Dynamics, Atherosclerosis and Bypass Graft Failure

    Microsoft Academic Search

    B. Lowell Langille; Matadial Ojha

    1997-01-01

    Atherosclerosis occurs at reproducible sites in the arterial tree and intimal proliferation that leads to bypass graft occlusion also show a well-defined focal distribution. These observations have led to the hypothesis that local blood flow conditions, especially low or fluctuating shear stresses, are important in the development of both disorders. Basic research using both cell culture and animal models has

  3. Obstructive Sleep Apnea, Immuno-Inflammation and Atherosclerosis

    E-print Network

    Paris-Sud XI, Université de

    Obstructive Sleep Apnea, Immuno-Inflammation and Atherosclerosis Claire Arnaud1,2 , Maurice;31(1):113-25" DOI : 10.1007/s00281-009-0148-5 #12;2 ABSTRACT Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder leading to cardiovascular and metabolic complications. OSA is also a multicomponent

  4. The role of shear stress in the pathogenesis of atherosclerosis

    Microsoft Academic Search

    Kristopher S Cunningham; Avrum I Gotlieb

    2005-01-01

    Although the pathobiology of atherosclerosis is a complex multifactorial process, blood flow-induced shear stress has emerged as an essential feature of atherogenesis. This fluid drag force acting on the vessel wall is mechanotransduced into a biochemical signal that results in changes in vascular behavior. Maintenance of a physiologic, laminar shear stress is known to be crucial for normal vascular functioning,

  5. The role of oxidative stress and autophagy in atherosclerosis.

    PubMed

    Perrotta, Ida; Aquila, Saveria

    2015-01-01

    Atherosclerosis is a multifactorial, multistep disorder of large- and medium-sized arteries involving, in addition to age, gender and menopausal status, a complex interplay between lifestyle and genetic risk factors. Atherosclerosis usually begins with the diffusion and retention of atherogenic lipoproteins into the subendothelial space of the artery wall where they become oxidized by local enzymes and accumulate, leading to the formation of a cushion called atheroma or atheromatous or fibrofatty plaque, composed of a mixture of macrophages, lymphocytes, smooth muscle cells (SMCs), cholesterol cleft, necrotic debris, and lipid-laden foam cells. The pathogenesis of atherosclerosis still remains incompletely understood but emerging evidence suggests that it may involve multiple cellular events, including endothelial cell (EC) dysfunction, inflammation, proliferation of vascular SMCs, matrix (ECM) alteration, and neovascularization. Actually, a growing body of evidence indicates that autophagy along with the chronic and acute overproduction of reactive oxygen species (ROS) is integral to the development and progression of the disease and may represent fruitful avenues for biological investigation and for the identification of new therapeutic targets. In this review, we give an overview of ROS and autophagy in atherosclerosis as background to understand their potential role in this vascular disease. PMID:25866599

  6. THE RELATION BETWEEN ATHEROSCLEROSIS AND INGESTED CHOLESTEROL IN THE RABBIT

    PubMed Central

    Clarkson, Sarah; Newburgh, L. H.

    1926-01-01

    1. The range of free cholesterol in the blood of rabbits, as determined by the Windaus method, varies from 35 to 125 mg. with a mean of 71 mg. per 100 cc. of blood. 2. The small amount of cholesterol contained in the high protein diet used by us in earlier work and causing atherosclerosis does not affect the blood cholesterol nor does it cause arterial disease. 3. In order to produce atherosclerosis it is necessary to feed at least ten times that amount of cholesterol. 4. In rabbits receiving such amounts both hypercholesterolemia and atherosclerosis occur, but it is not possible to establish any close parallelism between the two. High blood readings are found in rabbits with normal aortæ and atherosclerotic rabbits in this series sometimes have shown a normal blood cholesterol. 5. With still greater doses of cholesterol one finally reaches an amount which regularly produces hypercholesterolemia and atherosclerosis within a few weeks. 6. A new series of rabbits fed the high protein diet shows that those rabbits which become atherosclerotic also develop hypercholesterolemia. We attribute this elevation of the blood cholesterol to a metabolic disturbance directly referable to the excess of protein in the diet and not to its cholesterol content. PMID:19869147

  7. 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.

  8. 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.

  9. Inflammatory pathways in atherosclerosis and acute coronary syndromes

    Microsoft Academic Search

    Jorge Plutzky

    2001-01-01

    Evidence from a broad range of studies demonstrates that atherosclerosis is a chronic disease that, from its origins to its ultimate complications, involves inflammatory cells (T cells, monocytes, macrophages), inflammatory proteins (cytokines, chemokines), and inflammatory responses from vascular cells (endothelial cell expression of adhesion molecules). Investigators have identified a variety of proteins whose levels might predict cardiovascular risk. Of these

  10. Anti-inflammatory and antioxidant activities of the nonlipid (aqueous) components of sesame oil: potential use in atherosclerosis.

    PubMed

    Selvarajan, Krithika; Narasimhulu, Chandrakala Aluganti; Bapputty, Reena; Parthasarathy, Sampath

    2015-04-01

    Dietary intervention to prevent inflammation and atherosclerosis has been a major focus in recent years. We previously reported that sesame oil (SO) was effective in inhibiting atherosclerosis in low-density lipoprotein-receptor negative mice. We also noted that the levels of many proinflammatory markers were lower in the SO-treated animals. In this study we tested whether the non-lipid, aqueous components associated with SO would have anti-inflammatory and antioxidant effects. Polymerase chain reaction array data indicated that sesame oil aqueous extract (SOAE) was effective in reducing lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells. Expression of inflammatory cytokines such as interleukin (IL)-1?, IL-6, and tumor necrosis factor ? (TNF-?) was also analyzed independently in cells pretreated with SOAE followed by inflammatory assault. Effect of SOAE on TNF-?-induced MCP-1 and VCAM1 expression was also tested in human umbilical vein endothelial cells. We observed that SOAE significantly reduced inflammatory markers in both macrophages and endothelial cells in a concentration-dependent manner. SOAE was also effective in inhibiting LPS-induced TNF-? and IL-6 levels in vivo at different concentrations. We also noted that in the presence of SOAE, transcription and translocation of NF-kappaB was suppressed. SOAE was also effective in inhibiting oxidation of lipoproteins in vitro. These results suggest the presence of potent anti-inflammatory and antioxidant compounds in SOAE. Furthermore, SOAE differentially regulated expression of scavenger receptors and increased ATP-binding cassette A1 (ABCA1) mRNA expression by activating liver X receptors (LXRs), suggesting additional effects on lipid metabolism. Thus, SOAE appears multipotent and may serve as a valuable nonpharmacological agent in atherosclerosis and other inflammatory diseases. PMID:25692333

  11. 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 ...

  12. Dental and Periodontal Status and Risk for Progression of Carotid Atherosclerosis The Inflammation and Carotid Artery Risk for Atherosclerosis Study Dental Substudy

    Microsoft Academic Search

    Thomas Schillinger; Wolf Kluger; Markus Exner; Wolfgang Mlekusch; Schila Sabeti; Jasmin Amighi; Oswald Wagner; Erich Minar; Martin Schillinger

    2010-01-01

    Background and Purpose—Dental and periodontal disease are potentially involved in the pathogenesis of atherosclerosis. We investigated whether dental and periodontal status is associated with the presence and future progression of carotid stenosis. Methods—We randomly selected 411 of 1268 participants from the prospective Inflammation and Carotid Artery Risk for Atherosclerosis Study and evaluated dental and periodontal status and oral hygiene at

  13. 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

  14. 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

  15. Immune Effector Mechanisms Implicated in Atherosclerosis: From Mice to Humans

    PubMed Central

    Libby, Peter; Lichtman, Andrew H.; Hansson, Göran K.

    2013-01-01

    According to the traditional view, atherosclerosis results from a passive buildup of cholesterol in the artery wall. Yet, burgeoning evidence implicates inflammation and immune effector mechanisms in the pathogenesis of this disease. Both innate and adaptive immunity operate during atherogenesis and link many traditional risk factors to altered arterial functions. Inflammatory pathways have become targets in the quest for novel preventive and therapeutic strategies against cardiovascular disease, a growing contributor to morbidity and mortality worldwide. Here we review current experimental and clinical knowledge of the pathogenesis of atherosclerosis through an immunological lens and how host defense mechanisms essential for survival of the species actually contribute to this chronic disease but also present new opportunities for its mitigation. PMID:23809160

  16. Imaging of coronary atherosclerosis and identification of the vulnerable plaque

    PubMed Central

    de Feyter, P.J.; Serruys, P. W.; Nieman, K.; Mollet, N.; Cademartiri, F.; van Geuns, R. J.; Slager, C.; van der Steen, A.F.W.; Krams, R.; Schaar, J.A.; Wielopolski, P.; Pattynama, P.M.T.; Arampatzis, A.; van der Lugt, A.; Regar, E.; Ligthart, J.; Smits, P.

    2003-01-01

    Identification of the vulnerable plaque responsible for the occurrence of acute coronary syndromes and acute coronary death is a prerequisite for the stabilisation of this vulnerable plaque. Comprehensive coronary atherosclerosis imaging in clinical practice should involve visualisation of the entire coronary artery tree and characterisation of the plaque, including the three-dimensional morphology of the plaque, encroachment of the plaque on the vessel lumen, the major tissue components of the plaque, remodelling of the vessel and presence of inflammation. Obviously, no single diagnostic modality is available that provides such comprehensive imaging and unfortunately no diagnostic tool is available that unequivocally identifies the vulnerable plaque. The objective of this article is to discuss experience with currently available diagnostic modalities for coronary atherosclerosis imaging. In addition, a number of evolving techniques will be briefly discussed. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7 PMID:25696244

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

    PubMed Central

    Kim, YongTae; Lobatto, Mark E.; Kawahara, Tomohiro; Lee Chung, Bomy; Mieszawska, Aneta J.; Sanchez-Gaytan, Brenda L.; Fay, Francois; Senders, Max L.; Calcagno, Claudia; Becraft, Jacob; Tun Saung, May; Gordon, Ronald E.; Stroes, Erik S. G.; Ma, Mingming; Farokhzad, Omid C.; Fayad, Zahi A.; Mulder, Willem J. M.; Langer, Robert

    2014-01-01

    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 topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid–polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system. PMID:24395808

  18. Optical Molecular Imaging of Inflammation and Calcification in Atherosclerosis

    Microsoft Academic Search

    Elena Aikawa

    2010-01-01

    Optical molecular imaging represents an emerging method that can detect pathobiological processes in vivo at the cellular\\u000a and molecular levels, offering a dynamic link between imaging and biology. This review discusses the impact of molecular imaging\\u000a methods in atherosclerosis research and preventive medicine and focuses on the inflammation-dependent mechanisms of arterial\\u000a calcification.

  19. Nuclear Transport Modulation Reduces Hypercholesterolemia, Atherosclerosis, and Fatty Liver

    PubMed Central

    Liu, Yan; Major, Amy S.; Zienkiewicz, Jozef; Gabriel, Curtis L.; Veach, Ruth Ann; Moore, Daniel J.; Collins, Robert D.; Hawiger, Jacek

    2013-01-01

    Background Elevated cholesterol and triglycerides in blood lead to atherosclerosis and fatty liver, contributing to rising cardiovascular and hepatobiliary morbidity and mortality worldwide. Methods and Results A cell?penetrating nuclear transport modifier (NTM) reduced hyperlipidemia, atherosclerosis, and fatty liver in low?density lipoprotein receptor?deficient mice fed a Western diet. NTM treatment led to lower cholesterol and triglyceride levels in blood compared with control animals (36% and 53%, respectively; P<0.005) and liver (41% and 34%, respectively; P<0.05) after 8 weeks. Atherosclerosis was reduced by 63% (P<0.0005), and liver function improved compared with saline?treated controls. In addition, fasting blood glucose levels were reduced from 209 to 138 mg/dL (P<0.005), and body weight gain was ameliorated (P<0.005) in NTM?treated mice, although food intake remained the same as that in control animals. The NTM used in this study, cSN50.1 peptide, is known to modulate nuclear transport of stress?responsive transcription factors such as nuclear factor kappa B, the master regulator of inflammation. This NTM has now been demonstrated to also modulate nuclear transport of sterol regulatory element?binding protein (SREBP) transcription factors, the master regulators of cholesterol, triglyceride, and fatty acid synthesis. NTM?modulated translocation of SREBPs to the nucleus was associated with attenuated transactivation of their cognate genes that contribute to hyperlipidemia. Conclusions Two?pronged control of inflammation and dyslipidemia by modulating nuclear transport of their critical regulators offers a new approach to comprehensive amelioration of hyperlipidemia, atherosclerosis, fatty liver, and their potential complications. PMID:23563994

  20. Platelets and their chemokines in atherosclerosis—clinical applications

    PubMed Central

    von Hundelshausen, Philipp; Schmitt, Martin M. N.

    2014-01-01

    The concept of platelets as important players in the process of atherogenesis has become increasingly accepted due to accumulating experimental and clinical evidence. Despite the progress in understanding the molecular details of atherosclerosis, particularly by using animal models, the inflammatory and thrombotic roles of activated platelet s especially in the human system remain difficult to dissect, as often only the complications of atherosclerosis, i.e., stroke and myocardial infarction are definable but not the plaque burden. Platelet indices including platelet count and mean platelet volume (MPV) and soluble mediators released by activated platelets are associated with atherosclerosis. The chemokine CXCL4 has multiple atherogenic activities, e.g., altering the differentiation of T cells and macrophages by inhibiting neutrophil and monocyte apoptosis and by increasing the uptake of oxLDL and synergizing with CCL5. CCL5 is released and deposited on endothelium by activated platelets thereby triggering atherogenic monocyte recruitment, which can be attenuated by blocking the corresponding chemokine receptor CCR5. Atheroprotective and plaque stabilizing properties are attributed to CXCL12, which plays an important role in regenerative processes by attracting progenitor cells. Its release from luminal attached platelets accelerates endothelial healing after injury. Platelet surface molecules GPIIb/IIIa, GP1b?, P-selectin, JAM-A and the CD40/CD40L dyade are crucially involved in the interaction with endothelial cells, leukocytes and matrix molecules affecting atherogenesis. Beyond the effects on the arterial inflammatory infiltrate, platelets affect cholesterol metabolism by binding, modifying and endocytosing LDL particles via their scavenger receptors and contribute to the formation of lipid laden macrophages. Current medical therapies for the prevention of atherosclerotic therapies enable the elucidation of mechanisms linking platelets to inflammation and atherosclerosis. PMID:25152735

  1. Nikolai N. Anichkov and His Theory of Atherosclerosis

    PubMed Central

    Konstantinov, Igor E.; Mejevoi, Nicolai; Anichkov, Nikolai M.

    2006-01-01

    Nikolai N. Anichkov (1885–1964) first demonstrated the role of cholesterol in the development of atherosclerosis. His classic experiments in 1913 paved the way to our current understanding of the role of cholesterol in cardiovascular disease. Anichkov's research is often cited among the greatest discoveries of the 20th century; however, little is known about Anichkov and his team. Herein, we give a detailed historical account of Anichkov's work, his personality, his research team, and their pioneering effort. PMID:17215962

  2. Progress in HDL-Based Therapies for Atherosclerosis

    Microsoft Academic Search

    Kuang-Yuh Chyu; Anish Peter; Prediman K. Shah

    Atherosclerosis is a chronic inflammatory disease affecting medium and large arteries resulting from a complex interaction\\u000a between genetic and environmental risk factors that include dyslipidemia, hypertension, diabetes mellitus, and smoking. The\\u000a most serious manifestations of atherosclerotic vascular disease, such as unstable angina, myocardial infarction, ischemic\\u000a stroke, and sudden death, largely result from thrombosis superimposed on a disrupted (ruptured or eroded)

  3. 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

  4. P2 receptors in atherosclerosis and postangioplasty restenosis

    Microsoft Academic Search

    Cheikh I. Seye; Qiongman Kong; Ningpu Yu; Fernando A. Gonzalez; Laurie Erb; Gary A. Weisman

    2007-01-01

    Atherosclerosis is an immunoinflammatory process that involves complex interactions between the vessel wall and blood components\\u000a and is thought to be initiated by endothelial dysfunction [Ross (Nature 362:801–09, 1993); Fuster et al. (N Engl J Med 326:242–50,\\u000a 1992); Davies and Woolf (Br Heart J 69:S3–S11, 1993)]. Extracellular nucleotides that are released from a variety of arterial\\u000a and blood cells [Di

  5. [Extra-coronary atherosclerosis in documented coronary patients].

    PubMed

    Hodara, M; Bonithon-Kopp, C; Courbon, D; Guérin, F; Richard, J

    1998-02-01

    The prevalence and severity of extracoronary atherosclerosis in 728 patients (572 men and 156 women; average age 59 years) referred for coronary angiography and who had a history of coronary disease for at least 2 years, were assessed by ultrasonography. This population was divided into 3 groups: Group I, 115 patients without lesions at coronary angiography: Group II, 76 patients with mild coronary stenosis ang Group III, 537 patients with at least one severe coronary artery stenosis, a group which included 294 cases of single vessel disease. The authors observed a strong correlation between the presence, severity and diffusion of the coronary artery disease and ultra sonographic signs of peripheral arterial disease: the frequency increased regularly from 45% in Group I to 88% in patients with triple vessel disease in Group III. About two thirds of patients in Group III had carotid or lower limb atherosclerosis and half of them had atherosclerosis or aneurysm of the abdominal aorta. Severe peripheral lesions were not common but all the aortic aneurysms were observed in Group III. Similarly, simultaneous disease in all three peripheral arterial territories ranged from 12% in Group I to 51% in Group III. The risk of finding peripheral arterial disease was increased in patients with coronary artery disease compared with normal subjects. For each peripheral localisation, the risk was two-fold in cases of mild coronary disease and three or four-fold in patients with triple vessel disease in whom the risk of finding at least one severe peripheral lesion was multiplied by ten. The authors conclude that the prevalence and severity of ultrasonographic peripheral atherosclerosis in documented coronary patients was closely related to the presence, severity and diffusion of the coronary lesions. PMID:9749246

  6. Enalapril attenuates angiotensin II-induced atherosclerosis and vascular inflammation

    Microsoft Academic Search

    Valdeci da Cunha; Doris M. Tham; Baby Martin-McNulty; Gary Deng; Jerrick J. Ho; Dennis W. Wilson; John C. Rutledge; Ronald Vergona; Mark E. Sullivan

    2005-01-01

    Angiotensin converting enzyme (ACE) inhibitors prevent a wide variety of key events underlying atherogenesis. Whether these actions depend solely on reduction of angiotensin II (Ang II) generation is still to be determined. This study was undertaken to determine whether enalapril, an ACE inhibitor, prevents atherosclerosis and vascular inflammation induced by Ang II in apolipoprotein E-deficient (apoE-KO) mice. Subcutaneous infusion of

  7. Interferon-g and atherosclerosis: Pro or anti-atherogenic?

    Microsoft Academic Search

    Elizabeth J. Harvey; Dipak P. Ramji

    2005-01-01

    Atherosclerosis is considered to be a form of chronic inflammation governed by a complex network of inter- and intra-cellular signaling pathways. The pleiotropic cytokine interferon-g (IFN-g) is a key pro-inflammatory mediator that is expressed at high levels in atherosclerotic lesions. IFN-g regulates the function and properties of all the cell types in the vessel wall. The precise role of IFN-g

  8. 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

  9. Central role of the AT1-receptor in atherosclerosis

    Microsoft Academic Search

    G Nickenig

    2002-01-01

    The renin-angiotensin system plays a major role in the pathogenesis of atherosclerosis. Most known effects of angiotensin II are mediated via activation of the AT1-receptor, which is in turn influenced to a great degree by levels of expression of the AT1-receptor. AT1-receptor activation is not only involved in vasoconstriction, water and salt homoeostasis and control of other neurohumoral systems, but

  10. [Morphological aspects of atherosclerosis lesion: past and present].

    PubMed

    Gaudio, E; Carpino, G; Grassi, M; Musca, A

    2006-01-01

    Atherosclerosis is an inflammatory process disease that involves the artery wall and that is characterized by the progressive accumulation of lipids. The term arteriosclerosis has been created by Lobstein in 1833. Subsequently, during the 19th century, the contribution of Rokitansky and Virchow was important to elucidate the pathogenesis of arteriosclerosis and the morphologic aspects of the plaque. In the beginning of the 20th century, Aschoff was a leading proponent who regarded the morphologically different intimal lipid deposits of children and adults as early and late stages of one disease and he called them atherosis and atherosclerosis, respectively. The first classification of atherosclerosis was made by the World Health Organization (WHO) in 1958 and it consisted of the following sequence: fatty streak, atheroma, fibrous plaque and complicated lesions. In 1990s, thanks to much more sensitive techniques, the American Heart Association (AHA) proposed a new morphological classification based on eight lesion types designated by Roman numerals which indicate the usual sequence of lesion progression. Finally, Virmani et al. (2000) described a classification with the add of a specific plaque type, not recognized by the AHA classification, called "thin fibrous cap atheroma" which is more likely to rupture. The atherosclerotic process is characterized by typical ultrastructural changes that mainly involve the endothelial and smooth muscle cells. The morphological alterations of the endothelium are associated with dysfunctions leading to a proinflammatory and prothrombotic phenotype. This process seems to be due to turbulent blood flow and low fluid shear stress that normally occurs in particular regions of the vascular tree. Inflammation has a key role in the pathogenesis of atherosclerosis and it is supported by numerous factors such as modified LDL, hypertension, diabetes mellitus, free radicals and, in particular, by infectious agents such as Chlamydia pneumoniae. PMID:16817503

  11. Association between hepatitis C virus core protein and carotid atherosclerosis.

    PubMed

    Ishizaka, Yuko; Ishizaka, Nobukazu; Takahashi, Eiko; Unuma, Tadao; Tooda, Ei-ichi; Hashimoto, Hideki; Nagai, Ryozo; Yamakado, Minoru

    2003-01-01

    A link between certain infectious microorganisms and an increased risk of atherosclerotic disease has been suggested. By analyzing the data of subjects who had undergone general health-screening tests, a possible association between carotid atherosclerosis and seropositivity of antibody against hepatitis C virus (HCV) has been previously reported. In the present study, a possible link between carotid atherosclerosis and HCV core protein positivity was assessed, because it is postulated to be a better marker of viremia and thus persistent infection. Of the 1992 enrolled subjects, 496 (25%) had carotid artery plaque, and 25 (1.3%) were positive for HCV core protein. Carotid artery plaque was positive in 480/1967 (24%) and 16/25 (64%) of the core protein-negative and core protein-positive subjects, respectively (p<0.0001 by chi(2) test). Serum concentrations of transaminases were higher in core protein-positive subjects, but albumin concentrations were not significantly different between the 2 groups. Multivariate logistic regression analysis showed that HCV core protein positivity is an independent predictor of carotid plaque with an odds ratio of 5.61 (95% confidence interval 2.06-15.26, p<0.001). These data further support the possible link between persistent HCV infection and carotid atherosclerosis in the subjects without severe liver dysfunction. PMID:12520147

  12. LOX-1 in atherosclerosis: biological functions and pharmacological modifiers

    PubMed Central

    Xu, Suowen; Ogura, Sayoko; Chen, Jiawei; Little, Peter J.; Moss, Joel; Liu, Peiqing

    2013-01-01

    Lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1, also known as OLR-1), is a class E scavenger receptor that mediates the uptake of oxLDL by vascular cells. LOX-1 is involved in endothelial dysfunction, monocyte adhesion, the proliferation, migration, and apoptosis of smooth muscle cells, foam cell formation, platelet activation, as well as plaque instability; all of these events are critical in the pathogenesis of atherosclerosis. These LOX-1-dependent biological processes contribute to plaque instability and the ultimate clinical sequelae of plaque rupture and life-threatening tissue ischemia. Administration of anti-LOX-1 antibodies inhibits atherosclerosis by decreasing these cellular events. Over the past decade, multiple drugs including naturally occurring antioxidants, statins, antiinflammatory agents, antihypertensive and antihyperglycemic drugs have been demonstrated to inhibit vascular LOX-1 expression and activity. Therefore, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases. This review aims to integrate the current understanding of LOX-1 signaling, regulation of LOX-1 by vasculoprotective drugs, and the importance of LOX-1 in the pathogenesis of atherosclerosis. PMID:23124189

  13. Inflammation: a culprit for vascular calcification in atherosclerosis and diabetes.

    PubMed

    Bessueille, L; Magne, D

    2015-07-01

    It is today acknowledged that aging is associated with a low-grade chronic inflammatory status, and that inflammation exacerbates age-related diseases such as osteoporosis, Alzheimer's disease, atherosclerosis and type 2 diabetes mellitus (T2DM). Vascular calcification is a complication that also occurs during aging, in particular in association with atherosclerosis and T2DM. Recent studies provided compelling evidence that vascular calcification is associated with inflammatory status and is enhanced by inflammatory cytokines. In the present review, we propose on one hand to highlight the most important and recent findings on the cellular and molecular mechanisms of vascular inflammation in atherosclerosis and T2DM. On the other hand, we will present the effects of inflammatory mediators on the trans-differentiation of vascular smooth muscle cell and on the deposition of crystals. Since vascular calcification significantly impacts morbidity and mortality in affected individuals, a better understanding of its induction and development will pave the way to develop new therapeutic strategies. PMID:25746430

  14. The Relationship Between Lipids\\/Lipoproteins and Atherosclerosis in African Americans and Whites

    Microsoft Academic Search

    Paul D Sorlie; A. Richey Sharrett; Wolfgang Patsch; Pamela J Schreiner; Clarence E Davis; Gerardo Heiss; Richard Hutchinson

    1999-01-01

    PURPOSE: The relationships between lipids\\/lipoproteins and atherosclerosis were determined in African Americans and whites to assess the consistency of the relationship between these two groups. Differences could suggest varying biological, environmental, or life-style cofactors influencing development of atherosclerosis.METHODS: In the Atherosclerosis Risk in Communities Study, 2966 African Americans and 9399 whites had determinations of LDL, HDL, HDL2, and HDL3 cholesterol,

  15. Obstructive sleep apnoea as a risk factor for atherosclerosis – implication for preventive and personalised treatment

    Microsoft Academic Search

    Izabela Tuleta; Stefan Pabst; Uwe R. Juergens; Georg Nickenig; Dirk Skowasch

    2011-01-01

    Atherosclerosis with its manifestations and associated diseases is a main cause of morbidity and mortality in industrial countries.\\u000a The pathomechanisms underlying atherosclerosis are complex and comprise exogenous factors as well as genetic predisposition.\\u000a Beyond the well-defined risk factors for the development of atherosclerosis, obstructive sleep apnoea (OSA) merits more and\\u000a more attention. A growing body of evidence has associated OSA

  16. Anti-heat shock protein 70 autoantibody epitope changes and BD091 promotes atherosclerosis in rats

    Microsoft Academic Search

    Xue Leng; Rui Zhan; Yang Wang; Xiaohua Liu; Jingbo Gong; Xiujie Gao; Lei Wu; Liqun Wang; Yun Zhao; Xinxing Wang; Zhiqing Zhang; Wei Pang; Lingjia Qian

    2010-01-01

    It has been previously reported that the plasma levels of autoantibodies against heat shock protein 70 (HSP70) are elevated\\u000a in atherosclerosis. The aim of the present study was to elucidate whether anti-HSP70 antibodies are involved in the pathogenesis\\u000a of atherosclerosis. To determine this, we chose rats as an atherosclerosis model. Titers of plasma anti-HSP70 autoantibody\\u000a were determined by ELISA. After

  17. Atherosclerotic Risks from Chemicals: Part I. Toxicological Observations and Mechanisms of Atherosclerosis

    Microsoft Academic Search

    S. R. Basavaraju; T. D. Jones

    1998-01-01

    .   Atherosclerosis is a common disease, primarily of the large arteries, that begins in childhood and progresses with advancing\\u000a age. Atherosclerosis leads to coronary heart disease, the major cause of death in the United States. Several risk factors\\u000a affect atherosclerosis, but high LDL cholesterol is the most important risk factor. In addition, high levels of lipoprotein\\u000a (a) appear to be

  18. Attenuated atherosclerosis upon IL17R signaling disruption in LDLr deficient mice

    Microsoft Academic Search

    T. van Es; G. H. M. van Puijvelde; O. H. Ramos; F. M. E. Segers; L. A. B. Joosten; W. B. van den Berg; I. M. Michon; P. de Vos; Th. J. C. van Berkel; J. Kuiper

    2009-01-01

    Atherosclerosis is an inflammatory disease characterized by the influx of macrophages and T cells and IL-17 may connect innate and adaptive immune responses involved in atherogenesis. We investigated the role of IL-17 receptor signaling in atherosclerosis and transplanted LDLr deficient recipient mice with IL-17R deficient bone marrow. Induction of atherosclerosis by Western-type diet induced a 46% reduction in lesion size

  19. Lentiviral gene transfer to reduce atherosclerosis progression by long-term CC-chemokine inhibition

    Microsoft Academic Search

    C A Bursill; E McNeill; L Wang; O C Hibbitt; R Wade-Martins; D J Paterson; D R Greaves; K M Channon

    2009-01-01

    CC-chemokines are important mediators in the pathogenesis of atherosclerosis. Atherosclerosis progression is reduced by high-level, short-term inhibition of CC-chemokine activity, for example by adenoviral gene transfer. However, atherosclerosis is a chronic condition where short-term effects, while demonstrating proof-of-principle, are unlikely to provide maximum therapeutic benefit. Accordingly, we generated a recombinant lentivirus, lenti35K, encoding the broad-spectrum CC chemokine inhibitor, 35K, derived

  20. Prolactin receptor antagonism uncouples lipids from atherosclerosis susceptibility.

    PubMed

    van der Sluis, Ronald J; van den Aardweg, Tim; Reuwer, Anne Q; Twickler, Marcel T; Boutillon, Florence; Van Eck, Miranda; Goffin, Vincent; Hoekstra, Menno

    2014-09-01

    The pituitary-derived hormone prolactin has been suggested to stimulate the development of atherosclerosis and cardiovascular disease through its effects on metabolism and inflammation. In this study, we aimed to challenge the hypothesis that inhibition of prolactin function may beneficially affect atherosclerosis burden. Hereto, atherosclerosis-susceptible LDL receptor (Ldlr) knockout mice were transplanted with bone marrow from transgenic mice expressing the pure prolactin receptor antagonist Del1-9-G129R-hPRL or their non-transgenic littermates as control. Recipient mice expressing Del1-9-G129R-hPRL exhibited a decrease in plasma cholesterol levels (-29%; P<0.05) upon feeding a Western-type diet (WTD), which could be attributed to a marked decrease (-47%; P<0.01) in the amount of cholesterol esters associated with pro-atherogenic lipoproteins VLDL/LDL. By contrast, Del1-9-G129R-hPRL-expressing mice did not display any change in the susceptibility for atherosclerosis after 12 weeks of WTD feeding. Both the absolute atherosclerotic lesion size (223 ± 33 × 10(3)??m(2) for Del1-9-G129R-hPRL vs 259 ± 32 × 10(3)??m(2) for controls) and the lesional macrophage and collagen contents were not different between the two groups of bone marrow recipients. Importantly, Del1-9-G129R-hPRL exposure increased levels of circulating neutrophils (+91%; P<0.05), lymphocytes (+55%; P<0.05), and monocytes (+43%; P<0.05), resulting in a 49% higher (P<0.01) total blood leukocyte count. In conclusion, we have shown that prolactin receptor signaling inhibition uncouples the plasma atherogenic index from atherosclerosis susceptibility in Ldlr knockout mice. Despite an associated decrease in VLDL/LDL cholesterol levels, application of the prolactin receptor antagonist Del1-9-G129R-hPRL does not alter the susceptibility for initial development of atherosclerotic lesions probably due to the parallel increase in circulating leukocyte concentrations. PMID:25063756

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

    PubMed

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

    2015-08-01

    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

  2. Is excessive daytime sleepiness a predictor of carotid atherosclerosis in sleep apnea?

    Microsoft Academic Search

    Michael Saletu; Cornelia Sauter; Wolfgang Lalouschek; Bernd Saletu; Georg Kapfhammer; Thomas Benesch; Josef Zeitlhofer

    2008-01-01

    ObjectiveTo elucidate the relationship between excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA) and carotid atherosclerosis determined by ultrasonography and serum surrogate markers.

  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. Severity of atherosclerosis in parrots in relation to the intake of alpha-linolenic acid.

    PubMed

    Bavelaar, F J; Beynen, A C

    2003-01-01

    Atherosclerosis is a common disease among parrots, but little is known about possible risk factors. Important risk factors in humans are an elevated plasma cholesterol concentration and increased platelet aggregation; high intakes of polyunsaturated fatty acids have beneficial effects. In this study, we tried to establish a relationship, if any, between dietary fatty acids and the severity of atherosclerosis in parrots. We collected dead parrots and scored the degree of atherosclerosis in the beginning of the aorta and the brachiocephalic arteries. It was not possible to assess the intake of fatty acids with food questionnaires so fatty acid composition of adipose tissue and breast muscle had to be used as an index of the dietary fatty acid composition. In all, 202 birds were collected. Gender was not related with atherosclerosis, but the degree of atherosclerosis increased with age and among the various species; African grey parrots appeared to be the most susceptible. The contents of linoleic acid in breast muscle or adipose tissue were not associated with the severity of atherosclerosis. For the relative percentage of alpha-linolenic acid in either breast muscle (P = 0.09; n = 175) or adipose tissue (P = 0.056; n = 21), a borderline significant relation with the degree of atherosclerosis was found. Parrots without atherosclerosis had significantly higher levels of alpha-linolenic acid than did the other animals. On the basis of these data, we suggest tentatively that a high dietary intake of alpha-linolenic acid protects against the development of atherosclerosis in parrots. PMID:14562883

  5. Preventive Effect of Dipeptidyl Peptidase-4 Inhibitor on Atherosclerosis Is Mainly Attributable to Incretin's Actions in Nondiabetic and Diabetic Apolipoprotein E-Null Mice

    PubMed Central

    Terasaki, Michishige; Nagashima, Masaharu; Nohtomi, Kyoko; Kohashi, Kyoko; Tomoyasu, Masako; Sinmura, Kyoko; Nogi, Yukinori; Katayama, Yuki; Sato, Kengo; Itoh, Fumiko; Watanabe, Takuya; Hirano, Tsutomu

    2013-01-01

    Aim Several recent reports have revealed that dipeptidyl peptidase (DPP)-4 inhibitors have suppressive effects on atherosclerosis in apolipoprotein E-null (Apoe?/?) mice. It remains to be seen, however, whether this effect stems from increased levels of the two active incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Methods Nontreated Apoe?/? mice, streptozotocin-induced diabetic Apoe?/? mice, and db/db diabetic mice were administered the DPP-4 inhibitor vildagliptin in drinking water and co-infused with either saline, the GLP-1 receptor blocker, exendin(9–39), the GIP receptor blocker, (Pro3)GIP, or both via osmotic minipumps for 4 weeks. Aortic atherosclerosis and oxidized low-density lipoprotein-induced foam cell formation in exudate peritoneal macrophages were determined. Results Vildagliptin increased plasma GLP-1 and GIP levels without affecting food intake, body weight, blood pressure, or plasma lipid profile in any of the animals tested, though it reduced HbA1c in the diabetic mice. Diabetic Apoe?/? mice exhibited further-progressed atherosclerotic lesions and foam cell formation compared with nondiabetic counterparts. Nondiabetic and diabetic Apoe?/? mice showed a comparable response to vildagliptin, namely, remarkable suppression of atherosclerotic lesions with macrophage accumulation and foam cell formation in peritoneal macrophages. Exendin(9–39) or (Pro3)GIP partially attenuated the vildagliptin-induced suppression of atherosclerosis. The two blockers in combination abolished the anti-atherosclerotic effect of vildagliptin in nondiabetic mice but only partly attenuated it in diabetic mice. Vildagliptin suppressed macrophage foam cell formation in nondiabetic and diabetic mice, and this suppressive effect was abolished by infusions with exendin(9–39)+(Pro3)GIP. Incubation of DPP-4 or vildagliptin in vitro had no effect on macrophage foam cell formation. Conclusions Vildagliptin confers a substantial anti-atherosclerotic effect in both nondiabetic and diabetic mice, mainly via the action of the two incretins. However, the partial attenuation of atherosclerotic lesions by the dual incretin receptor antagonists in diabetic mice implies that vildagliptin confers a partial anti-atherogenic effect beyond that from the incretins. PMID:23967137

  6. Fluorescence spectroscopic detection of virus-induced atherosclerosis

    NASA Astrophysics Data System (ADS)

    Yan, Wei-dong; Perk, Masis; Nation, Patric N.; Power, Robert F.; Liu, Liying; Jiang, Xiuyan; Lucas, Alexandra

    1994-07-01

    Laser-induced fluorescence (LF) has been developed as a diagnostic tool for the detection of atherosclerosis. We have examined the use of LF for the identification of accelerated atherosclerotic plaque growth induced by Marek's Disease Virus (MDV) infection in White Leghorn rooster chicks (R) as well as plaque regression after treatment. Twenty-eight newborn R were infected with 12,000 cfu of MDV. Twelve parallel control R had saline injection. LF spectra were recorded from the arteries in vitro with a CeramOptec laser angioplasty catheter during 308 nm XeCl excimer laser excitation. Significant differences were detected at 440 to 475, 525, 550, 600, and 650 nm in MDV-R (p<0.05). In a subsequent study, 60 R were infected with 5,000 cfu of MDV, and were then treated with either Pravastatin (PRV) or placebo at 3 months post infection. These PRV-R were followed for 6 months to detect changes in atherosclerotic plaque development. PRV reduced intimal proliferation produced by MDV infection on histological examination (PRV-R 128.0+/- 44.0 micrometers , placebo-R 412.2+/- 91.5 micrometers , pequals0.007). MDV infected, PRV treated R were examined for LF changes that correlated with decreased atherosclerosis. There was an associated significant increase in LF intensity in PRV-R at 405 to 425 nm (p<0.001). In conclusion, LF can detect intimal proliferation in virus- induced atherosclerosis and atherosclerotic plaque regression after PRV therapy.

  7. Macrophage-mediated 15-lipoxygenase expression protects against atherosclerosis development.

    PubMed

    Shen, J; Herderick, E; Cornhill, J F; Zsigmond, E; Kim, H S; Kühn, H; Guevara, N V; Chan, L

    1996-11-15

    Oxidative modification of LDL increases its atherogenicity, and 15-lipoxygenase (15-LO) has been implicated in the process. To address this issue, we generated transgenic rabbits that expressed 15-LO in a macrophage-specific manner and studied their susceptibility to atherosclerosis development when they were fed a high-fat, high-cholesterol (HFHC) diet (Teklad 0533 rabbit diet 7009 with 10% corn oil and 0.25% cholesterol) for 13.5 wk. Transgenic and nontransgenic rabbits developed similar degrees of hypercholesterolemia and had similar levels of triglyceride, VLDL, LDL, and HDL. Quantitative morphometric analysis of the aortic atherosclerosis indicated that the transgenic animals (n = 19) had significantly smaller lesion areas (9.8+/-6.5%, mean+/-SD) than their littermate controls (n = 14, 17.8+/-15.0%) (P < 0.05). In a subgroup (n = 9) of transgenic rabbits that received the HFHC diet plus the antioxidant N',N '-diphenyl-phenylenediamine (1%), the extent of lesion involvement (9.8+/-7.5%) did not differ from the subgroup (n = 10) that received the regular HFHC diet (9.7+/-5.9%). Since the results were unexpected, we repeated the experiments. Again, we found that the nontransgenic littermates (n = 12) had more extensive lesions (11.6+/-10.6%) than the transgenic rabbits (n = 13; 9.5+/-7.8%), although the difference was not significant. In a third set of experiments, we crossed 15-LO transgenic rabbits with Watanabe heritable hyperlipidemic (WHHL) rabbits and found that the lesion area in the 15-LO transgenic/heterozygous WHHL rabbits (n = 14) was only about one third (7.7+/-5.7%) that found in nontransgenic heterozygous WHHL littermate controls (n = 11, 20.7+/-19.4%) (P < 0.05). These data suggest that overexpression of 15-LO in monocytes/macrophages protects against lipid deposition in the vessel wall during early atherogenesis in these rabbit models of atherosclerosis. PMID:8941635

  8. 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

  9. Syrian Hamster model of postmenopausal hypercholesterolemia atherosclerosis and the development of plaques as imaged by high field MRI

    E-print Network

    McQuade, D. Tyler

    Syrian Hamster model of postmenopausal hypercholesterolemia atherosclerosis and the development of flaxseed in a hamster model of postmenopausal atherosclerosis. The focus is to examine in vivo identification of plaques in cerebral arteries and aortas of overiectomized (ovx) hamsters with endogenous

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

    PubMed

    Son, Dong Ju; Kim, Soo Yeon; Han, Seong Su; Kim, Chan Woo; Kumar, Sandeep; Park, Byeoung Soo; Lee, Sung Eun; Yun, Yeo Pyo; Jo, Hanjoong; Park, Young Hyun

    2012-10-19

    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-?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?1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-?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. PMID:22995306

  11. Chronic Opisthorchis felineus infection attenuates atherosclerosis--an autopsy study.

    PubMed

    Magen, Eli; Bychkov, Vitaly; Ginovker, Alexander; Kashuba, Eduard

    2013-09-01

    Previously, we proposed a hypothesis that chronic helminthic infection may have beneficial effects on the development of atherosclerosis. The aim of this study was to investigate an association between Opisthorchis felineus chronic helminthic infections with aortic atherosclerosis and serum total cholesterol. A series of medico-legal autopsy specimens collected in Khanty-Mansiisk (the region in Russia endemic for O. felineus) were studied to assess O. felineus worm burden in cadaver livers. The areas of atherosclerotic lesions in the cadaver aortas were measured by visual planimetry. A family history of cardiovascular disease, smoking, hypertension or diabetes was elicited, and serum total cholesterol levels examined. Three hundred and nineteen cadavers (280 (87.8%) males and 39 (12.2%) females) aged 20-72 years were divided into five age groups: (i) 20-29, (ii) 30-39, (iii) 40-49, (iv) 50-59 and (v) >60 years old. The O. felineus mean worm burden was 257±312 worms/liver. Infected subjects were categorised into three subgroups depending on the worm burden: mild (<100 worms), moderate (100-500 worms) and severe (>500 worms). Infected subjects had lower serum total cholesterol (mild worm burden, 186.4±25.6 mg/dl; moderate worm burden, 183.4±23.1mg/dl, P=0.002; severe worm burden, 170.6±25.1mg/dl, P<0.001) than non-infected subjects (201.1±21.2 mg/dl). The average percentage of aortic surface covered by fatty streaks, fibrotic plaques and complicated lesions was negatively related to worm burden in the infected subjects. Chronic helminthic infections was a negative predictor of aortic atherosclerosis; with an odds ratio of 1.72 (1.02-2.91), P=0.041 for all subjects; and 3.19 (1.35-7.58), P=0.008 for subjects aged >40 years old. Opisthorchis felineus chronic helminthic infectionswas found to be associated with lower serum total cholesterol levels and a significant attenuation of atherosclerosis. PMID:23792298

  12. 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

  13. Preventive Effect of hydroalcoholic extract of Silybum marianum and fumaria vaillantii in atherosclerosis

    Microsoft Academic Search

    Objectives: Atherosclerosis is a disease of the vascular system that produces a gradual deposition of lipids in large and medium arteries. This disease is the most common cause of death in the world.The increase in cholesterol is an important factor in development of atherosclerosis. Epidemiological studies have shown significant and positive affinity between total cholesterol and LDL cholesterol of serum

  14. Bioinformatic transcriptomic analysis of ApoE deficient mice suggests Alterations in atherosclerosis related molecular mechanisms

    Microsoft Academic Search

    Olga Papadodima; Aristotelis Chatziioanou; Allan Sirsjo; Fragiskos N. Kolisis

    2010-01-01

    Atherosclerosis is a multifactorial disease involving a lot of genes and proteins recruited throughout its manifestation. The present study represents an integrative effort, coupling the results of a bioinformatic analysis based on microarray data of atherosclerotic aortic lesions of apoE knockout mice, a model widely used in atherosclerosis research, together with gene expression measurements of human atherosclerotic lesions. A dynamic

  15. The inextricable link between atherosclerosis and prototypical inflammatory diseases rheumatoid arthritis and systemic lupus erythematosus

    Microsoft Academic Search

    Louise E Full; Cristina Ruisanchez; Claudia Monaco

    2009-01-01

    The increased burden of cardiovascular disease in patients with rheumatoid arthritis and systemic lupus erythematosus has recently become the focus of intense investigation. Proatherogenic risk factors and dysregulated inflammation are the main culprits, leading to enhanced atherosclerosis in subgroups of patients with inflammatory diseases. Common molecular pathways shared by atherosclerosis and inflammatory disease may be involved. In this review we

  16. Serum matrix metalloproteinase-2 and increased oxidative stress are associated with carotid atherosclerosis in hemodialyzed patients

    Microsoft Academic Search

    Krystyna Pawlak; Dariusz Pawlak; Michal Mysliwiec

    2007-01-01

    Matrix metalloproteinases (MMPs)\\/their inhibitors (TIMPs) system and elevated oxidative stress (SOX) have been implicated as important factors in atherosclerosis and vascular remodeling. The aim of the present study was to investigate whether MMPs\\/TIMPs system is associated with SOX in hemodialyzed (HD) patients. We compared the serum levels of metalloproteinases and their inhibitors, markers of SOX, inflammation and atherosclerosis between HD

  17. 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…

  18. Sleep and Biomarkers of Atherosclerosis in Elderly Alzheimer Caregivers and Controls

    Microsoft Academic Search

    Roland von Känel; Sonia Ancoli-Israel; Joel E. Dimsdale; Paul J. Mills; Brent T. Mausbach; Michael G. Ziegler; Thomas L. Patterson; Igor Grant

    2010-01-01

    Background: Perturbed sleep might contribute to cardiovascular disease by accelerating atherosclerosis. Sleep is poor in Alzheimer caregivers who are also a group at increased cardiovascular risk. Objective: To test the hypothesis that impaired sleep relates to elevated levels of biomarkers of atherosclerosis in community-dwelling elderly and that this association would possibly be stronger in caregivers than in non-caregiving controls. Methods:

  19. The Enigma of Genetics Etiology of Atherosclerosis in the Post-GWAS Era

    PubMed Central

    Marian, A.J.

    2012-01-01

    Coronary atherosclerosis is a complex heritable trait with an enigmatic genetic etiology. Genome-wide association studies (GWAS) have successfully led to identification of over 100 different loci for susceptibility to coronary atherosclerosis. Most identified single nucleotide polymorphisms (SNP)s and genes have not been previously implicated in the pathogenesis of atherosclerosis and hence, have modest biological plausibility. The novel discoveries, however, might provide the opportunity for identification of new pathways and consequently novel preventive and therapeutic targets. A notable outcome of GWAS is relatively modest effect sizes of the associated SNPs. Collectively, the identified SNPs account for a relatively small fraction of heritability of coronary atherosclerosis, which raises the question of “missing heritability”. Because GWAS test the common disease – comment variant hypothesis, a plausible explanation might be the presence of uncommon and rare variants in the genome that are untested in GWAS but that might exert large effect sizes on the risk of atherosclerosis. The latter, however, remains an empiric question pending validation through experimentation. Alternative mechanisms, such as transgenerational epigenetics including microRNAs, might in part account for the heritability of coronary atherosclerosis. Collectively, the recent findings are indicative of the etiological complexity of coronary atherosclerosis. Hence, it is expected that genetic etiology of coronary atherosclerosis will remain enigmatic in the foreseeable future. PMID:22437283

  20. Natural Androgens Inhibit Male Atherosclerosis A Study in Castrated, Cholesterol-Fed Rabbits

    Microsoft Academic Search

    Peter Alexandersen; Jens Haarbo; Inger Byrjalsen; Henrik Lawaetz; Claus Christiansen

    The effect of natural androgens on serum lipids and atherosclerosis is controversial. We therefore studied this important issue prospectively in an animal model of atherosclerosis. Eighty male rabbits were randomized to bilateral castration, and 20 animals were sham operated. The castrated rabbits were randomized to 500 mg oral dehydroepiandrosterone (DHEA) daily, 80 mg oral testosterone undecanoate (TU) daily, or 25-mg

  1. Atherosclerosis and ischemic cardiomyopathy in a captive, adult red-tailed hawk (Buteo jamaicensis).

    PubMed

    Shrubsole-Cockwill, Alana; Wojnarowicz, Chris; Parker, Dennilyn

    2008-09-01

    An adult, male, captive red-tailed hawk (Buteo jamaicensis) of at least 19 years of age presented in dorsal recumbency. The hawk was nonresponsive, and despite initial supportive care, died shortly after presentation. Gross postmortem revealed no abnormal findings. Histologic examination demonstrated atherosclerosis and ischemic cardiomyopathy. This is the first reported case of atherosclerosis in a red-tailed hawk. PMID:18939649

  2. 75 FR 62544 - Proposed Collection; Comment Request; the Atherosclerosis Risk in Communities Study (ARIC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ...Atherosclerosis Risk in Communities Study (ARIC) SUMMARY: In...Atherosclerosis Risk in Communities Study (ARIC). Type of Information...participants in the ARIC study, review of their medical...aged and older men and women. Frequency of Response...accuracy of the agency's estimate of the...

  3. 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

    ...Atherosclerosis Risk in Communities Study (ARIC) Summary: Under...Atherosclerosis Risk in Communities Study (ARIC). Type of Information...participants in the ARIC study, review of their medical...aged and older men and women. Frequency of Response...assuming respondent's time at the rate...

  4. Atherosclerosis in angiographically “normal” coronary artery reference segments: An intravascular ultrasound study with clinical correlations

    Microsoft Academic Search

    Gary S. Mintz; Jack A. Painter; Augusto D. Pichard; Kenneth M. Kent; Lowell F. Satler; Jeffrey J. Popma; Ya Chien Chuang; Theresa A. Bucher; Lisa E. Sokolowicz; Martin B. Leon

    1995-01-01

    Objectives. This study evaluated the magnitude, patterns and clinical correlates of atherosclerosis in angiographically “normal” reference segments in patients undergoing transcatheter therapy for symptomatic coronary artery disease.Background. Pathologic studies indicate that the extent of coronary atherosclerosis is underestimated by visual analysis of angiographically normal coronary artery segments. Intravascular ultrasound allows detailed, high quality cross-sectional imaging of the coronary arteries in

  5. Role of polymorphonuclear neutrophils in atherosclerosis: Current state and future perspectives

    Microsoft Academic Search

    Roberta Baetta; Alberto Corsini

    2010-01-01

    Contrary to the long-standing and widely accepted belief that polymorphonuclear neutrophils (PMN) are of marginal relevance in atherosclerosis, evidence revealing a previously unappreciated role of PMN in the process of atherosclerosis is being accumulating. Systemic inflammation involving activated PMN is clearly associated with unstable conditions of coronary artery disease and an increased number of circulating neutrophils is a well-known risk

  6. Mechanisms of Disease: macrophage-derived foam cells emerging as therapeutic targets in atherosclerosis

    Microsoft Academic Search

    Justin M Lee; David R Greaves; Robin P Choudhury

    2005-01-01

    The limited efficacy of current treatment strategies for targeting atherosclerosis and its complications requires new therapeutic options to be explored. From early fatty-streak lesions to advanced plaques, macrophage-derived foam cells are integral to the development and progression of atherosclerosis. Elucidation of molecular and cellular processes involving macrophages has led to numerous therapeutic targets being suggested. Potential sites of intervention range

  7. The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes

    Microsoft Academic Search

    Raffaele Marfella; Michele D' Amico; Clara Di Filippo; Mario Siniscalchi; Ferdinando Carlo sasso; Franca Ferraraccio; Francesco Rossi; Giuseppe Paolisso

    2007-01-01

    We have reviewed the impact of the ubiquitin proteasome system (UPS) on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its role in the removal of damaged proteins, is involved in a number of biological processes including inflammation, proliferation and apoptosis, all of which constitute important characteristics of atherosclerosis. From

  8. Thermal bottomonium suppression

    NASA Astrophysics Data System (ADS)

    Strickland, Michael

    2013-03-01

    I discuss recent calculations of the thermal suppression of bottomonium states in relativistic heavy ion collisions. I present results for the inclusive ?(1s) and ?(2s) suppression as a function of centrality. I compare with the most recent CMS preliminary data available at central rapidities and make predictions at forward rapidities which are within the acceptance of the ALICE dimuon spectrometer.

  9. Interleukin6 Promoter Polymorphism Modulates the Effects of Heavy Alcohol Consumption on Early Carotid Artery Atherosclerosis The Carotid Atherosclerosis Progression Study (CAPS)

    Microsoft Academic Search

    Paula Jerrard-Dunne; Matthias Sitzer; Paul Risley; Donata A. Steckel; Alexandra Buehler; Stefan von Kegler; Hugh S. Markus

    2010-01-01

    Background and Purpose—A J-shaped relationship has been demonstrated between alcohol and both clinical cardiovas- cular events and carotid atherosclerosis. A similar J-shaped relationship has been found between alcohol intake and inflammatory markers. If inflammation were on the intermediate causal pathway between alcohol intake and atherosclerosis, then genetic determinants of enhanced inflammation would be expected to modify this relationship. Methods—In a

  10. Blood level of osteonectin in stenosing atherosclerosis and calcinosis of coronary arteries.

    PubMed

    Ragino, Yu I; Kashtanova, E V; Chernjavski, A M; Volkov, A M; Polonskaya, Ya V; Tsimbal, S Yu; Eremenko, N V; Ivanova, M V

    2011-07-01

    Blood levels of stem cell marker proteins CD34 and osteonectin were studied in male patients with coronary atherosclerosis by direct biomagnetic separation of proteins with magnetic microspheres using the PureProteome Protein A and Protein G Magnetic Beads proteomic technology. High concentration of osteonectin in the blood was detected, particularly in men with stenosing atherosclerosis and coronary artery calcinosis. Blood osteonectin concentration correlated significantly with some key biomarkers of atherosclerosis and with stenosing atherosclerosis and calcinosis of coronary arteries. The results indicate that osteonectin as a marker of stromal stem cells with osteogenic potential presumably plays an important role in atherogenesis and can serve as a new biomarker of stenosing atherosclerosis and calcinosis of coronary arteries. PMID:22451890

  11. PPAR activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH

    E-print Network

    Boyer, Edmond

    : Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are complex pathologies characterized by lipid levels in a tissue-specific manner. Keywords : microparticles, atherosclerosis, fatty liver disease are pathophysiologically related to atherosclerosis and non-alcoholic fatty liver disease (NAFLD), including non

  12. Proposed Synergistic Effect of Calcium Channel Blockers with Lipid-Lowering Therapy in Retarding Progression of Coronary Atherosclerosis

    Microsoft Academic Search

    J. Wouter Jukema; Ad J. van Boven; Aeilko H. Zwinderman; Arnoud Van der Laarse; Albert V. G. Bruschke

    1998-01-01

    Lipid-lowering therapy now has undoubtedly proven to be an effective therapeutic modality to retard the progression of coronary atherosclerosis. An additional approach for prevention of the progression of atherosclerosis is calcium channel blocker (CCB) treatment. Evidence indicating that CCBs inhibit atherosclerosis is less unequivocal than the clear evidence for lipid-lowering therapy. Many investigations support the view that a number of

  13. 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

  14. [Atherosclerosis and uremia: signifance of non-traditional risk factors].

    PubMed

    Hörl, Walter H

    2003-04-30

    Arteriosclerosis, atherosclerosis and vascular calcification are causally related to the high morbidity and mortality of patients with chronic renal failure. Oxidative stress and carbonyl stress of uremia, dialysis procedure and/or intravenous iron therapy result in AGE (advanced glycation end-product), ALE (advanced lipoxidation end-product) and AOPP (advanced oxidation protein product) formation, favouring together with elevated CRP (C-reactive protein) levels the development of cardiovascular and cerebrovascular complications. Enhanced plasma levels of homocysteine and ADMA (asymmetric dimethylarginine) contribute to this process. In addition, in chronic renal insufficiency hyperphosphatemia and an enhanced calcium x phosphorus ion product are associated with the morbidity and mortality of the patients, particularly in the presence of fetuin deficiency. Phosphorus, AGEs and AOPPs, beside other factors, catalyze the conversion of vascular smooth muscle cells to osteoblast--like cells (particularly in the presence of monocytes/macrophages), resulting in bone matrix protein formation. Other risk factors, such as age, male sex, smoking, hypertension, diabetes, chronic inflammation, insulin resistance or dyslipidemia (enhanced non-HDL-cholesterol) also contribute to the atherosclerotic risk profile of the patient with chronic renal insufficiency. While there is growing understanding of the mechanisms involved in arteriosclerosis, atherosclerosis and vascular calcification in uremia, we are still missing effective therapeutic maneuvers for reduction of excess mortality in uremic patients. PMID:12778774

  15. TNFalpha in atherosclerosis, myocardial ischemia/reperfusion and heart failure.

    PubMed

    Kleinbongard, Petra; Heusch, Gerd; Schulz, Rainer

    2010-09-01

    TNFalpha is crucially involved in the pathogenesis and progression of atherosclerosis, myocardial ischemia/reperfusion injury and heart failure. The formation and release of TNFalpha and its downstream signal transduction cascade following activation of its two receptor subtypes is characterized, with special emphasis on the cardiovascular system. In the vasculature, TNFalpha alters endothelial and vascular smooth muscle cell function as well as endothelial cell-blood cell interaction; the importance of such alterations for vascular dysfunction, the initiation and progression of atherosclerosis are discussed. In the myocardium, TNFalpha contributes to reversible and irreversible ischemia/reperfusion injury, post-myocardial infarction remodeling and heart failure development. Simultaneously, TNFalpha also contributes to cardioprotection by ischemic conditioning. Emphasis is placed on such ambivalent (detrimental vs. beneficial) role of TNFalpha, which appears to be dose- and time-dependent and in part related to the activation of the specific receptor subtype. Given the ambivalent role of TNFalpha and its receptors, it is not surprising that clinical trials using compounds that antagonize TNFalpha revealed ambiguous and largely disappointing results in cardiovascular disease, notably in heart failure. Future perspectives to antagonize and/or potentially recruit TNFalpha in the cardiovascular system are critically discussed. PMID:20621692

  16. Zebrafish models of dyslipidemia: Relevance to atherosclerosis and angiogenesis

    PubMed Central

    Fang, Longhou; Liu, Chao; Miller, Yury I.

    2013-01-01

    Lipid and lipoprotein metabolism in zebrafish and in humans are remarkably similar. Zebrafish express all major nuclear receptors, lipid transporters, apolipoproteins and enzymes involved in lipoprotein metabolism. Unlike mice, zebrafish express cetp and the Cetp activity is detected in zebrafish plasma. Feeding zebrafish a high cholesterol diet, without any genetic intervention, results in significant hypercholesterolemia and robust lipoprotein oxidation, making zebrafish an attractive animal model to study mechanisms relevant to early development of human atherosclerosis. These studies are facilitated by the optical transparency of zebrafish larvae and the availability of transgenic zebrafish expressing fluorescent proteins in endothelial cells and macrophages. Thus, vascular processes can be monitored in live animals. In this review article we discuss recent advances in using dyslipidemic zebrafish in atherosclerosis-related studies. We also summarize recent work connecting lipid metabolism with regulation of angiogenesis, the work that considerably benefited from using the zebrafish model. These studies uncovered the role of aibp, abca1, abcg1, mtp, apoB and apoC2 in regulation of angiogenesis in zebrafish and paved the way for future studies in mammals, which may suggest new therapeutic approaches to modulation of excessive or diminished angiogenesis contributing to the pathogenesis of human disease. PMID:24095954

  17. Update on medical management of dyslipidemia and atherosclerosis.

    PubMed

    Ginter, E; Simko, V

    2013-01-01

    Scientific achievements revealing the pathogenesis of atherosclerosis resulted in the second half of the 20th century in major improvement in prevention and therapy of cardiovascular disorders (CVD). Essential became the understanding of a critical pathogenetic role of the low-density lipoproteins (LDL), mainly their oxidized form (oxLDL) and also the protective potential of the high-density lipoproteins (HDL). CVD is now regarded to be an inflammatory disease in which a systemic inflammatory reaction is combined with an accumulation of immune cells in atherosclerotic plaques. Higher intake of antioxidants in fruit and vegetable, life style modifications, cessation of smoking, physical exercise and introduction of medications that lower LDL and promote HDL (statins, niacin and fibrates) resulted in a substantial decline of the killer effect of unmanaged CVD. In the United Kingdom the male CVD mortality declined between 1970 and 2009 from 700 to 200 deaths per 100,000. In France, CVD mortality in the middle age population (25-64 years) is now responsible for death in only 15 % men and in 11 % women. Unfortunately, in many parts of the world CVD mortality remains a prominent population scourge. Recent discoveries, especially on the role of peroxisome proliferator-activated receptors (PPAR) and antisense compounds used in addition to established anti-atherogenic medications, promise further gains in the fight against atherosclerosis (Fig. 4, Ref. 54). PMID:23611048

  18. Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches.

    PubMed

    Siasos, Gerasimos; Tsigkou, Vasiliki; Kokkou, Eleni; Oikonomou, Evangelos; Vavuranakis, Manolis; Vlachopoulos, Charalambos; Verveniotis, Alexis; Limperi, Maria; Genimata, Vasiliki; Papavassiliou, Athanasios G; Stefanadis, Christodoulos; Tousoulis, Dimitris

    2014-01-01

    It has been clear that at least 1 billion adults worldwide are smokers and at least 700 million children are passive smokers at home. Smoking exerts a detrimental effect to many organ systems and is responsible for illnesses such as lung cancer, pneumonia, chronic obstructive pulmonary disease, cancer of head and neck, cancer of the urinary and gastrointestinal tract, periodontal disease, cataract and arthritis. Additionally, smoking is an important modifiable risk factor for the development of cardiovascular disease such as coronary artery disease, stable angina, acute coronary syndromes, sudden death, stroke, peripheral vascular disease, congestive heart failure, erectile dysfunction and aortic aneurysms via initiation and progression of atherosclerosis. A variety of studies has proved that cigarette smoking induces oxidative stress, vascular inflammation, platelet coagulation, vascular dysfunction and impairs serum lipid pro-file in both current and chronic smokers, active and passive smokers and results in detrimental effects on the cardiovascular system. The aim of this review is to depict the physical and biochemical properties of cigarette smoke and, furthermore, elucidate the main pathophysiological mechanisms of cigarette-induced atherosclerosis and overview the new therapeutic approaches for smoking cessation and augmentation of cardiovascular health. PMID:25174928

  19. Visfatin/PBEF and atherosclerosis-related diseases.

    PubMed

    Filippatos, Theodosios D; Randeva, Harpal S; Derdemezis, Christos S; Elisaf, Moses S; Mikhailidis, Dimitri P

    2010-01-01

    Visfatin is highly expressed in adipose tissue (mainly by the stromal cells), but it is also ubiquitously present in most tissues. Visfatin, which plays a role in nicotinamide adenine dinucleotide (NAD) biosynthesis, has been implicated in inflammatory states. Controversial results exist about the expression, circulating levels and the role of visfatin in atherosclerosis-related diseases. Most studies showed increased levels of visfatin in diabetes mellitus, obesity, hypertension, renal and cardiovascular disease. However, other studies reported lower levels of visfatin in these diseases. The discrepancies in clinical studies may be attributed to the multifactorial regulation of visfatin. There is evidence that visfatin expression and circulating levels are influenced by fat area and distribution, inflammatory state, renal function, iron metabolism, hormones as well as several other factors. Furthermore, discrepancies and lack of correlation between commercially available visfatin assays have been reported. More research is needed to better understand the factors that control its synthesis/release and to evaluate the role of visfatin in atherosclerosis-related disease. Large studies with homogeneous populations will probably be needed to answer these questions. Whether visfatin will eventually become a therapeutic target remains to be established. PMID:19485930

  20. 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.

  1. Spectroscopic intravascular photoacoustic imaging of lipids in atherosclerosis.

    PubMed

    Jansen, Krista; van der Steen, Antonius F W; Wu, Min; van Beusekom, Heleen M M; Springeling, Geert; Li, Xiang; Zhou, Qifa; Shung, K Kirk; de Kleijn, Dominique P V; van Soest, Gijs

    2014-02-01

    The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the diseased arterial wall. As lesions become more vulnerable, different cholesterol species accumulate in the plaque. Understanding unstable atherosclerosis as a pharmacological and interventional therapeutic target requires chemically specific imaging of disease foci. In this study, we aim to image atherosclerotic plaque lipids and other vessel wall constituents with spectroscopic intravascular photoacoustics (sIVPA). sIVPA imaging can identify lipids in human coronary atherosclerotic plaque by relying on contrast in the near-infrared absorption spectra of the arterial wall components. Using reference spectra acquired on pure compounds, we analyzed sIVPA data from human coronary plaques ex vivo, to image plaque composition in terms of cholesterol and cholesterol ester content. In addition, we visualized the deeper lying connective tissue layers of the adventitia, as well as the fatty acid containing adipose cells in the peri-adventitial tissue. We performed simultaneous coregistered IVUS imaging to obtain complementary morphological information. Results were corroborated by histopathology. sIVPA imaging can distinguish the most prevalent lipid components of human atherosclerotic plaques and also visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the peri-adventitial tissue. PMID:24522806

  2. 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.

  3. Obstructive coronary atherosclerosis and ischemic heart disease: an elusive link!

    PubMed

    Marzilli, Mario; Merz, C Noel Bairey; Boden, William E; Bonow, Robert O; Capozza, Paola G; Chilian, William M; DeMaria, Anthony N; Guarini, Giacinta; Huqi, Alda; Morrone, Doralisa; Patel, Manesh R; Weintraub, William S

    2012-09-11

    In the current pathophysiological model of chronic ischemic heart disease (IHD), myocardial ischemia and exertional angina are caused by obstructive atherosclerotic plaque, and the clinical management of IHD is centered on the identification and removal of the stenosis. Although this approach has been in place for years, several lines of evidence, including poor prognostic impact, suggest that this direct relationship may present an oversimplified view of IHD. Indeed, a large number of studies have found that IHD can occur in the presence or absence of obstructive coronary artery disease and that atherosclerosis is just 1 element in a complex multifactorial pathophysiological process that includes inflammation, microvascular coronary dysfunction, endothelial dysfunction, thrombosis, and angiogenesis. Furthermore, the high recurrence rates underscore the fact that removing stenosis in patients with stable IHD does not address the underlying pathological mechanisms that lead to the progression of nonculprit lesions. The model proposed herein shifts the focus away from obstructive epicardial coronary atherosclerosis and centers it on the microvasculature and myocardial cell where the ischemia is taking place. If the myocardial cell is placed at the center of the model, all the potential pathological inputs can be considered, and strategies that protect the cardiomyocytes from ischemic damage, regardless of the causative mechanism, can be developed. PMID:22954239

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

    SciTech Connect

    Son, Dong Ju [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States) [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Kim, Soo Yeon [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of)] [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of); Han, Seong Su [University of Iowa Carver College of Medicine, Department of Pathology, Iowa City, IA (United States)] [University of Iowa Carver College of Medicine, Department of Pathology, Iowa City, IA (United States); Kim, Chan Woo [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States) [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Kumar, Sandeep [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States) [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Park, Byeoung Soo [Nanotoxtech Co., Ansan (Korea, Republic of)] [Nanotoxtech Co., Ansan (Korea, Republic of); Lee, Sung Eun [Division of Applied Biology and Chemistry, Kyungpook National University, Daegu (Korea, Republic of)] [Division of Applied Biology and Chemistry, Kyungpook National University, Daegu (Korea, Republic of); Yun, Yeo Pyo [College of Pharmacy, Chungbuk National University, Cheongju (Korea, Republic of)] [College of Pharmacy, Chungbuk National University, Cheongju (Korea, Republic of); Jo, Hanjoong, E-mail: hjo@emory.edu [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States) [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Park, Young Hyun, E-mail: pyh012@sch.ac.kr [Department of Food Science and Nutrition, College of Natural Sciences, Soonchunhyang University, Asan (Korea, Republic of)

    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.

  5. Hail suppression and society.

    PubMed

    Changnon, S A; Farhar, B C; Swanson, E R

    1978-04-28

    An interdisciplinary assessment of hail suppression in the past, present, and future has shown it to be currently scientifically uncertain but a potentially beneficial future technology. An established suppression technology would be widely adopted in the Great Plains, providing benefits to agriculture and secondarily to the American consumer. Development of a reliable technology will require a sizable longterm federal commitment to atmospheric and social research. Subcritical funding would be a mistake. Orderly future usage of hail suppression, with its scientific complexities and regional character, will necessitate development of governmental regulations, evaluation procedures, interstate arrangements, and means for compensating those who lose from modification. PMID:17757286

  6. 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

  7. 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

  8. Plasma Cholesterol–Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis

    PubMed Central

    Björkegren, Johan L. M.; Hägg, Sara; Jain, Rajeev K.; Cedergren, Cecilia; Shang, Ming-Mei; Rossignoli, Aránzazu; Takolander, Rabbe; Melander, Olle; Hamsten, Anders; Michoel, Tom; Skogsberg, Josefin

    2014-01-01

    Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (?80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr?/?Apob100/100Mttpflox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. PMID:24586211

  9. Triacetyl-3-hydroxyphenyladenosine, a derivative of cordycepin, attenuates atherosclerosis in apolipoprotein E-knockout mice.

    PubMed

    Zhao, Zhenmei; Song, Guohua; Tian, Hua; Yu, Yang; Tian, Xiangyu; Liu, Jia; Yao, Shutong; Luo, Tian; Qin, Shucun

    2012-11-01

    The cholesterol-modulating, immune-regulating and anti-inflammatory properties of cordycepin are well documented. Here we examined the effects of triacetyl-3-hydroxyphenyladenosine (THPA), a derivative of cordycepin, on the development of atherosclerosis (AS) in apolipoprotein E-knockout (apoE(-/-)) mice. The atherosclerotic lesion formation displayed by the oil red O staining-positive area was reduced significantly in either the aortic root section or the whole aorta en face in THPA-administrated apoE(-/-) mice. Plasma analysis by enzymatic method or enzyme-linked immunosorbent assay (ELISA) showed that high-density lipoprotein-cholesterol (HDL-C) was decreased, whereas apolipoprotein A-I (apoA-I) levels were markedly increased by THPA. In addition, ELISA and spectrophotometric measurement showed that plasma levels of tumor necrosis factor-?, interleukin-1 and malondialdehyde were decreased in mice treated with THPA. Realtime polymerase chain reaction detection disclosed that the expression of several transporters involved in reverse cholesterol transport was induced by THPA, and the expression of hepatic ABCA1 and apoA-I, which play roles in the maturation of HDL-C, was also elevated in the THPA-treated groups. Moreover, THPA enhanced the expression of endothelial nitric oxide synthase (NOS), and reduced the expression of inducible NOS and lectin-like oxidized LDL receptor-1 in the aorta, suggesting that THPA can exert endothelial protection effects. In addition, the expression or activation of several proinflammatory factors in the aorta was suppressed by THPA. In conclusion, our results reveal the inhibitory effects of THPA on AS in apoE(-/-) mice. PMID:23239437

  10. Dynamic Aspects of Macrophage Polarization during Atherosclerosis Progression and Regression

    PubMed Central

    Peled, Michael; Fisher, Edward A.

    2014-01-01

    It is well recognized that macrophages in many contexts in vitro and in vivo display a spectrum of inflammatory features and functional properties. A convenient system to group together different subsets of macrophages has been the M1 (inflammatory)/M2 (anti-inflammatory) classification. In addition to other sites of inflammation, it is now established that atherosclerotic plaques contain both M1 and M2 macrophages. We review results made possible by a number of recent mouse models of atherosclerotic regression that, taken with other literature, have shown the M1/M2 balance in plaques to be dynamic, with M1 predominating in disease progression and M2 in regression. The regulation of the macrophage phenotype in plaques and the functional consequences of the M1 and M2 states in atherosclerosis will also be discussed. PMID:25429291

  11. Extracellular matrix synthesis in vascular disease: hypertension, and atherosclerosis

    PubMed Central

    Ponticos, Markella; Smith, Barbara D.

    2014-01-01

    Extracellular matrix (ECM) within the vascular network provides both a structural and regulatory role. The ECM is a dynamic composite of multiple proteins that form structures connecting cells within the network. Blood vessels are distended by blood pressure and, therefore, require ECM components with elasticity yet with enough tensile strength to resist rupture. The ECM is involved in conducting mechanical signals to cells. Most importantly, ECM regulates cellular function through chemical signaling by controlling activation and bioavailability of the growth factors. Cells respond to ECM by remodeling their microenvironment which becomes dysregulated in vascular diseases such hypertension, restenosis and atherosclerosis. This review examines the cellular and ECM components of vessels, with specific emphasis on the regulation of collagen type I and implications in vascular disease. PMID:24474961

  12. Mechanisms of Premature Atherosclerosis in Rheumatoid Arthritis and Lupus

    PubMed Central

    Kahlenberg, J. Michelle; Kaplan, Mariana J.

    2014-01-01

    Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), the two most common systemic autoimmune disorders, have both unique and overlapping manifestations. One feature they share is a significantly enhanced risk of atherosclerotic cardiovascular (CV) disease that significantly contributes to morbidity and mortality. The primary mechanisms that drive CV damage in these diseases remain to be fully characterized, but recent discoveries indicate that distinct inflammatory pathways and immune dysregulation characteristic of RA and SLE likely play prominent roles. This review focuses on analyzing the major mechanisms and pathways potentially implicated in the acceleration of atherothrombosis [**AU: Should this be atherosclerosis for consistency?**] and CV risk in SLE and RA, as well as in the identification of putative preventive strategies that may mitigate vascular complications in systemic autoimmunity. PMID:23020882

  13. Soluble TWEAK independently predicts atherosclerosis in renal transplant patients

    PubMed Central

    2013-01-01

    Background Cardiovascular risk is increased in the early stages of chronic kidney disease (CKD) and also found to be ongoing in renal transplant (Rtx) patients. As a sign of atherosclerosis, increased carotid intima-media thickness (CIMT) has been widely accepted as a strong predictor of cardiovascular disease (CVD) and mortality in CKD patients. A novel markers, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and neutrophil-to-lymphocyte ratio (NLR) were introduced as potential markers in inflammatory disorders including CKD. The role of Rtx in terms of atherogenesis is still unclear. We aimed to investigate the relationship between sTWEAK, NLR and CIMT in Rtx patients without overt CVD and to compare these results with those obtained from healthy subjects. Methods Cross-sectional analysis in which CIMT measurements, NLR and serum TWEAK levels were assessed in 70 Rtx patients (29 females; mean age, 40.6?±?12.4 years) and 25 healthy subjects (13 females, mean age; 37.4±8.8 years). Results sTWEAK levels were significantly decreased (p=0.01) and hs-CRP, NLR and CIMT levels of Rtx patients were significantly increased compared to healthy subjects (p<0.0001, p=0.001, p<0.0001, respectively). sTWEAK was also found to be decreased when eGFR was decreased (p=0.04 between all groups). CIMT was positively correlated with sTWEAK and NLR in Rtx patients (r=0.81, p<0.0001 and r=0.33, p=0.006, respectively). sTWEAK was also positively correlated with NLR (r=0.37, p=0.002). In the multivariate analysis only sTWEAK was found to be an independent variable of increased CIMT. Conclusion sTWEAK might have a role in the pathogenesis of ongoing atherosclerosis in Rtx patients. PMID:23849432

  14. Flow Shear Stress and Atherosclerosis: A Matter of Site Specificity

    PubMed Central

    Nigro, Patrizia; Abe, Jun-ichi

    2011-01-01

    Abstract It is well accepted that atherosclerosis occurs in a site-specific manner especially at branch points where disturbed blood flow (d-flow) predisposes to the development of plaques. Investigations both in vivo and in vitro have shown that d-flow is pro-atherogenic by promoting oxidative and inflammatory states in the artery wall. In contrast, steady laminar blood flow (s-flow) is atheroprotective by inhibition of oxidative stress and inflammation in the vessel wall. The mechanism for inflammation in endothelial cells (ECs) exposed to d-flow has been well studied and includes redox-dependent activation of apoptosis signal-regulating kinase 1 (ASK1) and Jun NH2-terminal kinase (JNK) that ultimately lead to the expression of adhesive molecules. In contrast, s-flow leads to the activation of the mitogen extracellular-signal-regulated kinase kinase 5/extracellular signal-regulated kinase-5 (MEK5/ERK5) pathway that prevents pro-inflammatory signaling. Important transcriptional events that reflect the pro-oxidant and pro-inflammatory condition of ECs in d-flow include the activation of activator protein 1 (AP-1) and nuclear factor kappaB (NF?B), whereas in s-flow, activation of Krüppel-like factor 2 (KLF2) and nuclear factor erythroid 2-like 2 (Nrf2) are dominant. Recent studies have shown that protein kinase c zeta (PKC?) is highly activated under d-flow conditions and may represent a molecular switch for EC signaling and gene expression. The targeted modulation of proteins activated in a site-specific manner holds the promise for a new approach to limit atherosclerosis. Antioxid. Redox Signal. 15, 1405–1414. PMID:21050140

  15. Shear stress and advanced atherosclerosis in human coronary arteries.

    PubMed

    Gijsen, Frank; van der Giessen, Alina; van der Steen, Anton; Wentzel, Jolanda

    2013-01-18

    The role of low and oscillating shear stress as a key factor for localizing early atherosclerotic plaques is generally accepted. Once more advanced plaques protrude into the lumen, the shear stress they are exposed to changes. The influence of shear stress on plaque composition in advanced atherosclerosis is not fully understood. In this review, we discuss our recent studies on the relationship between shear stress and plaque composition and the location of plaque rupture in human coronary arteries. We have shown that elevated shear stress levels can be found over plaques inducing only mild luminal narrowing and are not subjected to treatment. Regional exposure of certain plaque regions to high shear stress is therefore a condition that will pertain for a prolonged period of time. We have also shown that in more advanced atherosclerosis the necrotic core experiences higher shear stress. Low shear stress plaque regions can be found downstream of the plaque and are stiffer. High shear stress plaque regions can be found either at the upstream, shoulder or cap region of the plaque and are softer. The plaque regions with the highest strain levels are the regions that are exposed to the highest shear stress. The high shear stress plaque regions are the only plaque regions that get softer over time. Finally, high shear stress is also associated with the location of plaque rupture in non-culprit lesion in human coronary arteries. Combining our findings with data from literature, we can conclude that advanced coronary plaques grow in the distal regions. The distal plaque regions are exposed to low shear stress, are stiffer and have a stable plaque phenotype. The regions exposed to high shear stress are softer, and are associated with vulnerable plaque features. PMID:23261245

  16. PDGFR? signalling regulates local inflammation and synergizes with hypercholesterolaemia to promote atherosclerosis.

    PubMed

    He, Chaoyong; Medley, Shayna C; Hu, Taishan; Hinsdale, Myron E; Lupu, Florea; Virmani, Renu; Olson, Lorin E

    2015-01-01

    Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for vascular smooth muscle cells (VSMCs). However, the direct effects of PDGF receptor ? (PDGFR?) activation on VSMCs have not been studied in the context of atherosclerosis. Here we present a new mouse model of atherosclerosis with an activating mutation in PDGFR?. Increased PDGFR? signalling induces chemokine secretion and leads to leukocyte accumulation in the adventitia and media of the aorta. Furthermore, PDGFR?(D849V) amplifies and accelerates atherosclerosis in hypercholesterolemic ApoE(-/-) or Ldlr(-/-) mice. Intriguingly, increased PDGFR? signalling promotes advanced plaque formation at novel sites in the thoracic aorta and coronary arteries. However, deletion of the PDGFR?-activated transcription factor STAT1 in VSMCs alleviates inflammation of the arterial wall and reduces plaque burden. These results demonstrate that PDGFR? pathway activation has a profound effect on vascular disease and support the conclusion that inflammation in the outer arterial layers is a driving process for atherosclerosis. PMID:26183159

  17. Understanding the role of B cells in atherosclerosis: potential clinical implications.

    PubMed

    Morris-Rosenfeld, Samuel; Lipinski, Michael J; McNamara, Coleen A

    2014-01-01

    Atherosclerosis is a progressive inflammatory disease of the medium to large arteries that is the largest contributor to cardiovascular disease. B-cell subsets have been shown in animal models of atherosclerosis to have both atherogenic and atheroprotective properties. In this review, we highlight the research that developed our understanding of the role of B cells in atherosclerosis both in humans and mice. From this we discuss the potential clinical impact B cells could have both as diagnostic biomarkers and as targets for immunotherapy. Finally, we recognize the inherent difficulty in translating findings from animal models into humans given the differences in both cardiovascular disease and the immune system between mice and humans, making the case for greater efforts at addressing the role of B cells in human atherosclerosis. PMID:24308836

  18. Protective role of 11?-HSD1 inhibition in the metabolic syndrome and atherosclerosis 

    E-print Network

    Wamil, Ma?gorzata

    2009-01-01

    glucocorticoid levels, generated by the intracellular enzyme 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) are also implicated in the pathogenesis of obesity, metabolic syndrome and atherosclerosis. Transgenic mice over-expressing 11?-HSD1 selectively...

  19. Promotion of atherosclerosis by Helicobacter cinaedi infection that involves macrophage-driven proinflammatory responses.

    PubMed

    Khan, Shahzada; Rahman, H N Ashiqur; Okamoto, Tatsuya; Matsunaga, Tetsuro; Fujiwara, Yukio; Sawa, Tomohiro; Yoshitake, Jun; Ono, Katsuhiko; Ahmed, Khandaker Ahtesham; Rahaman, Md Mizanur; Oyama, Kohta; Takeya, Motohiro; Ida, Tomoaki; Kawamura, Yoshiaki; Fujii, Shigemoto; Akaike, Takaaki

    2014-01-01

    Helicobacter cinaedi is the most common enterohepatic Helicobacter species that causes bacteremia in humans, but its pathogenicity is unclear. Here, we investigated the possible association of H. cinaedi with atherosclerosis in vivo and in vitro. We found that H. cinaedi infection significantly enhanced atherosclerosis in hyperlipidaemic mice. Aortic root lesions in infected mice showed increased accumulation of neutrophils and F4/80(+) foam cells, which was due, at least partly, to bacteria-mediated increased expression of proinflammatory genes. Although infection was asymptomatic, detection of cytolethal distending toxin RNA of H. cinaedi indicated aorta infection. H. cinaedi infection altered expression of cholesterol receptors and transporters in cultured macrophages and caused foam cell formation. Also, infection induced differentiation of THP-1 monocytes. These data provide the first evidence of a pathogenic role of H. cinaedi in atherosclerosis in experimental models, thereby justifying additional investigations of the possible role of enterohepatic Helicobacter spp. in atherosclerosis and cardiovascular disease. PMID:24732347

  20. 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

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

    Microsoft Academic Search

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

    2011-01-01

    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.

  2. Correlations between measures of atherosclerosis change using carotid ultrasonography and coronary angiography

    Microsoft Academic Search

    Wendy J. Mack; Laurie LaBree; Chao-Ran Liu; Chi-Hua Liu; Robert H. Selzer; Howard N. Hodis

    2000-01-01

    Few studies have examined the correlation between change in carotid artery intima-media thickness (IMT) and change in coronary artery disease. In the Cholesterol Lowering Atherosclerosis Study, current nonsmoking men with coronary artery disease were randomized to colestipol-niacin or placebo. Among 133 subjects with baseline and on-trial coronary angiography and carotid ultrasonography, colestipol-niacin treatment significantly reduced progression of atherosclerosis by both

  3. Role of oxidized low-density lipoprotein in the atherosclerosis of uremia

    Microsoft Academic Search

    Tilman B. Drueke; THAO NGUYEN KHOA; Ziad A. Massy; VÉRONIQUE WITKO-SARSAT; BERNARD LACOUR; BÉATRICE DESCAMPS-LATSCHA

    2001-01-01

    Role of oxidized low-density lipoprotein in the atherosclerosis of uremia. Lipoprotein oxidation is involved in the genesis of atherosclerosis. In chronic renal failure (CRF), oxidative stress is enhanced because of an imbalance between pro-oxidant and antioxidant systems. Oxidative modifications of low-density lipoproteins (LDLs) occur not only at the level of lipid moiety, but also of protein moiety. We have shown

  4. Ineffectiveness of Ca2+-Antagonists Nicardipine and Diltiazem on Experimental Atherosclerosis in Cholesterol-fed Rabbits

    Microsoft Academic Search

    Michitaka Naito; Fumio Kuzuya; Kan-ichi Asai; Kazuaki Shibata; Noboru Yoshimine

    1984-01-01

    There is accumulating evidence that calcium metabolism plays an important role in the pathogenesis of atherosclerosis. The inhibitory effect of nifedipine, a Ca2-antagonist, on experimental atherosclerosis in cholesterol-fed rabbits has been reported, and we examined the anti-atherosclerotic action of nicardipine and diltiazem, similar Ca2+-antagonists, but no inhibitory action was observed.It is necessary to recognize the fact that the sensitivity of

  5. Inflammatory Gene Load Is Associated With Enhanced Inflammation and Early Carotid Atherosclerosis in Smokers

    Microsoft Academic Search

    Paula Jerrard-Dunne; Matthias Sitzer; Paul Risley; Alexandra Buehler; Stefan von Kegler; Hugh S. Markus

    2010-01-01

    Background and Purpose—Smoking acts as a pro-inflammatory stimulus. Inflammation may provide a key mechanism by which smoking causes atherosclerosis. If so, then the degree to which an individual mounts an inflammatory response is likely to influence atherosclerosis severity. This study examined the impact of inflammatory gene polymorphisms and gene-smoking interactions on common carotid artery intima-media thickness (IMT), a measure of

  6. Protective Role of CXC Receptor 4\\/CXC Ligand 12 Unveils the Importance of Neutrophils in Atherosclerosis

    Microsoft Academic Search

    Alma Zernecke; Ilze Bot; Yassin Djalali-Talab; Erdenechimeg Shagdarsuren; Kiril Bidzhekov; Svenja Meiler; Regina Krohn; Andreas Schober; Markus Sperandio; Oliver Soehnlein; Jorg Bornemann; Frank Tacke; Erik A. Biessen; Christian Weber

    2010-01-01

    Abstract—The CXC ligand (CXCL)12\\/CXC receptor (CXCR)4 chemokine–receptor axis controls hematopoiesis, organ development, and angiogenesis, but its role in the inflammatory pathogenesis of atherosclerosis is unknown. Here we show that interference with Cxcl12\\/Cxcr4 by a small-molecule antagonist, genetic Cxcr4 deficiency, or lentiviral transduction with Cxcr4 degrakine in bone marrow,chimeras aggravated diet-induced atherosclerosis in apolipoprotein E-deficient (Apoe,) mice. Chronic blockade of Cxcr4

  7. Noninvasive screening for coronary atherosclerosis and silent ischemia in asymptomatic high-risk populations

    Microsoft Academic Search

    George A. Beller

    2009-01-01

    Asymptomatic subjects at risk for adverse cardiovascular events, based on clinical risk models, are further risk-stratified\\u000a by noninvasive imaging of coronary atherosclerosis and silent ischemia. Coronary atherosclerosis can be detected by imaging\\u000a coronary artery calcification (CAC). CAC scores more than 400 are associated with a higher cardiac event rate. Silent ischemia\\u000a can be detected by stress perfusion imaging employing single

  8. The Use of Animal Models to Study Diabetes and Atherosclerosis and Potential AntiAtherosclerotic Therapies

    Microsoft Academic Search

    Peter D. Reaven; Wulf Palinski

    Epidemiological studies have documented that individuals with diabetes mellitus (DM) and those with impaired glucose tolerance\\u000a (IGT) have an increased prevalence of atherosclerosis and increased rates of coronary artery disease (CAD) (1,2). However, the mechanisms by which these conditions enhance atherogenesis are poorly understood. Hyperglycemia, the defining\\u000a metabolic change in diabetes, may contribute to the development of atherosclerosis. However, the

  9. Relation of vessel wall shear stress to atherosclerosis progression in human coronary arteries.

    PubMed

    Gibson, C M; Diaz, L; Kandarpa, K; Sacks, F M; Pasternak, R C; Sandor, T; Feldman, C; Stone, P H

    1993-02-01

    The purpose of this study was to determine the relation between vessel wall shear stress and the rate of atherosclerosis progression. Quantitative angiography was used to calculate the change in coronary arterial diameter over 3.0 years in patients enrolled in the Harvard Atherosclerosis Reversibility Project pilot study (n = 20 arterial segments). Vessel wall shear stress was calculated by means of a validated finite-difference model of the Navier-Stokes' equation that assumes a coronary flow rate of 8 ml/sec. The correlation between vessel wall shear stress and the change in arterial diameter at multiple points (mean, 70) along the length of the artery was then calculated for each of the 20 segments with a focal stenosis. In 15 of the 20 arterial segments there was a significant correlation (p < 0.05) between low shear stress and an increased rate of atherosclerosis progression. A Fisher's z transformation was then used to combine the correlation coefficients from all 20 segments. Low shear stress was significantly correlated (z = 0.37 +/- 0.00074, p < 0.0001) with an increased rate of atherosclerosis progression. This serial quantitative evaluation of human coronary arteries is consistent with previous data that have suggested that low shear stress promotes atherosclerosis progression. Variations in local vessel wall shear stress may explain the previously reported near-independent rate of atherosclerosis progression in multiple lesions within the same patient despite exposure to the same circulating lipoprotein values and systemic hemodynamics. PMID:8427866

  10. T-bet deficiency reduces atherosclerosis and alters plaque antigen-specific immune responses

    PubMed Central

    Buono, Chiara; Binder, Christoph J.; Stavrakis, George; Witztum, Joseph L.; Glimcher, Laurie H.; Lichtman, Andrew H.

    2005-01-01

    The influence of the immune system on atherosclerosis involves both helper T (Th) cell and antibody responses to plaque antigens. These responses may have proatherogenic and protective effects. T-bet is a transcription factor required for Th1 differentiation and regulates the balance between Th1 and Th2 responses in inflammatory diseases. To clarify how helper T cell subset differentiation influences atherosclerosis, we compared lesion development and immune responses to plaque antigens in low-density lipoprotein receptor-deficient (Ldlr-/-) mice with or without functional T-bet genes. Atherosclerosis was significantly reduced in T-bet-deficient Ldlr-/- mice compared with Ldlr-/- controls, and the lesions that did develop in the absence of T-bet had less smooth muscle cell content. Furthermore, T-bet deficiency caused a Th2 switch in the response to the atherosclerosis-associated antigen heat shock protein-60, and a change in T-dependent isotypes of oxidized LDL-specific antibodies. Of particular significance, T-bet deficiency caused a >250% increase in the titer of E06 antibodies, which are known to be atheroprotective and whose production by B-1 B cells is enhanced by IL-5. These findings establish that T cell subset differentiation influences both T cell and antibody responses that modulate atherosclerosis, and validate the therapeutic goal of skewing T responses to atherosclerosis-associated antigens. PMID:15665085

  11. The role of oxidized low-density lipoproteins in atherosclerosis: the myths and the facts.

    PubMed

    Maiolino, Giuseppe; Rossitto, Giacomo; Caielli, Paola; Bisogni, Valeria; Rossi, Gian Paolo; Calò, Lorenzo A

    2013-01-01

    The oxidative modification hypothesis of atherosclerosis, which assigns to oxidized low-density lipoproteins (LDLs) a crucial role in atherosclerosis initiation and progression, is still debated. This review examines the role played by oxidized LDLs in atherogenesis taking into account data derived by studies based on molecular and clinical approaches. Experimental data carried out in cellular lines and animal models of atherosclerosis support the proatherogenic role of oxidized LDLs: (a) through chemotactic and proliferating actions on monocytes/macrophages, inciting their transformation into foam cells; (b) through stimulation of smooth muscle cells (SMCs) recruitment and proliferation in the tunica intima; (c) through eliciting endothelial cells, SMCs, and macrophages apoptosis with ensuing necrotic core development. Moreover, most of the experimental data on atherosclerosis-prone animals benefiting from antioxidant treatment points towards a link between oxidative stress and atherosclerosis. The evidence coming from cohort studies demonstrating an association between oxidized LDLs and cardiovascular events, notwithstanding some discrepancies, seems to point towards a role of oxidized LDLs in atherosclerotic plaque development and destabilization. Finally, the results of randomized clinical trials employing antioxidants completed up to date, despite demonstrating no benefits in healthy populations, suggest a benefit in high-risk patients. In conclusion, available data seem to validate the oxidative modification hypothesis of atherosclerosis, although additional proofs are still needed. PMID:24222937

  12. ADMA/SDMA in Elderly Subjects with Asymptomatic Carotid Atherosclerosis: Values and Site-Specific Association

    PubMed Central

    Riccioni, Graziano; Scotti, Luca; D’Orazio, Nicolantonio; Gallina, Sabina; Speziale, Giuseppe; Speranza, Lorenza; Bucciarelli, Tonino

    2014-01-01

    Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA values and site-specific association of asymptomatic carotid atherosclerosis (intima-media thickness (CIMT) and plaque) in elderly subjects. One hundred and eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI). All subjects had no acute or chronic symptoms of carotid atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA were positively correlated to carotid atherosclerosis (CIMT and plaque) (p < 0.001), with significant site-specific association. Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p < 0.001). High serum concentrations of ADMA and SDMA were associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and may represent a new marker of asymptomatic carotid atherosclerosis in elderly subjects. PMID:24739810

  13. Relation between Birth Weight, Growth, and Subclinical Atherosclerosis in Adulthood

    PubMed Central

    Valente, Maria Helena; Gomes, Filumena Maria da Silva; Benseñor, Isabela Judith Martins; Brentani, Alexandra Valéria Maria; Escobar, Ana Maria de Ulhôa; Grisi, Sandra J. F. E.

    2015-01-01

    Background and Objectives. Adverse conditions in the prenatal environment and in the first years of life are independently associated with increased risk for cardiovascular disease. This paper aims to study the relation between birthweight, growth in the first year of life, and subclinical atherosclerosis in adults. Methods. 88 adults aged between 20 and 31 were submitted to sociodemographic qualities, anthropometric data, blood pressure measurements, metabolic profile, and evaluation of subclinical atherosclerosis. Results. Birthweight <2,500 grams (g) was negatively correlated with (a) increased waist-to-hip ratio (WHR), according to regression coefficient (RC) equal to ?0.323, 95% CI [?0.571, ?0.075] P < 0.05; (b) diastolic blood pressure (RC = ?4.744, 95% CI [?9.017, ?0.470] P < 0.05); (c) low HDL-cholesterol (RC = ?0.272, 95% CI [?0.516, ?0.029] P < 0.05); (d) frequency of intima-media thickness (IMT) of left carotid >75th percentile (RC = ?0.242, 95% CI [?0.476, ?0.008] P < 0.05). Birthweight >3,500?g was associated with (a) BMI >25.0?kg/m2, (RC = 0.317, 95% CI [0.782, 0.557] P < 0.05); (b) increased waist circumference (RC = 0.284, 95% CI [0.054, 0.513] P < 0.05); (c) elevated WHR (RC = 0.280, 95% CI [0.054, 0.505] P < 0.05); (d) minimum subcutaneous adipose tissue (SAT) (RC = 4.354, 95% CI [0.821, 7.888] P < 0.05); (e) maximum SAT (RC = 7.095, 95% CI [0.608, 13.583] P < 0.05); (f) right lobe of the liver side (RC = 6.896, 95% CI [1.946, 11.847] P < 0.001); (g) frequency's right lobe of the liver >75th percentile (RC = 0.361, 95% CI [0.169, 0.552] P < 0.001). Weight gain in the first year of life was inversely correlated with (a) mean IMT of left carotid (RC = ?0.046, 95% CI [?0.086, ?0.006] P < 0.05; (b) frequency IMT of left carotid >75th percentile (RC = ?0.253, 95% CI [?0.487, ?0.018] P < 0.05); (c) mean IMT (RC = ?0.038, 95% CI [0.073, ?0.002] P < 0.05); (d) the frequency of the mean IMT >75th percentile (RC = ?0.241, 95% CI [?0.442, ?0.041] P < 0.05). Conclusions. Adults birthweight <2,500?g and >3,500?g and with insufficient weight gain in the first year of life have showed different metabolic phenotypes, but all of them were related to subclinical atherosclerosis. PMID:25648854

  14. Quantitative coronary cineangiography for the study of atherosclerosis.

    PubMed

    Brunt, J N; Watts, G F; Lewis, B; Smith, L D; Coltart, D J

    1995-07-01

    Angiography is the definitive procedure for characterising the extent and course of coronary artery disease. We describe the methodology required to measure, with optimal resolving power, angiographic changes in coronary artery disease. We utilised recent technological developments in image digitization, storage and analysis. The measures of change quantified both diffuse and focal atherosclerosis. Frames from angiographic cine films were digitized at high resolution (1024 x 1024 pixels, 8 bit grey scale) and archived on optical disk. Four radiographic projections were stored to ensure good visualization of as many as possible of a set of ten major arterial segments. Edges of segments and catheter were automatically delineated by computer using a dynamic programming algorithm involving a cost function which contained terms based on edge strength and on continuity. For every digitized radiographic projection, delineation was repeated in three adjacent frames, to improve precision. Edge points for each coronary segment were stored on disk. From these we computed the mean width along the segment (pixels). Scaling to obtain the Mean Absolute Width of the Segment (MAWS, mm) was achieved using catheter dimensions known from micrometry, systematic error due to imaging system line-spread function being corrected using data from computer simulations and phantom studies. Correction for geometric image intensifier distortion was also applied. We used the methodology in a randomized, controlled trial of the effect of lipid-lowering therapy, the St Thomas' Atherosclerosis Regression Study. The fundamental measure of change of disease in each segment was the change in MAWS (delta MAWS). Using in-vitro and in-vivo studies we established that the overall resolving power for one segment delta MAWS was 0.10 mm at 2 mm width and 0.14 mm at 4 mm width. Subsidiary end-points were the change (delta) in minimum absolute width of segment (MinAWS), edge irregularity index (EII) and percent diameter stenosis (%DS). Delta%DS (the conventional angiographic measure of coronary disease) was significantly correlated with change in all indices, closest correlation being seen with delta EII (r = 0.94, p < 0.001). PMID:7670695

  15. Turbulence Suppression by Shear

    E-print Network

    suppression when , the ¦§© shearing rate, is on the order of the linear growth rate or a turbulent §© flow only intro- duces a doppler shift, and is not included here. By introducing the variable with the #12;equilibrium flow, the %'p)21 365 term is introduced, consistent with smooth statistically

  16. Studies on the Effects of Diets Realistic for Westernized People on Plasma Lipoprotein Composition, Metabolism, and Atherosclerosis in Vervet Monkeys

    Microsoft Academic Search

    Ambrose J. Spinnler Benadé

    Using diets realistic for Westernized people, which consist entirely of normal foods for humans, has added to our knowledge\\u000a regarding the impact of diet on plasma lipoprotein metabolism and atherosclerosis in Vervet monkeys. The overall effect of\\u000a a Western atherogenic diet (WAD) on the progression and a prudent diet (PD) on the regression of atherosclerosis were confirmed.\\u000a Although atherosclerosis is

  17. Juxtarenal aortic atherosclerosis. Surgical experience and functional result.

    PubMed Central

    Stoney, R J; Skiöldebrand, C G; Qvarfordt, P G; Reilly, L M; Ehrenfeld, W K

    1984-01-01

    Ninety patients underwent combined aortic (90) and renal artery (138 arteries) reconstruction for severe, symptomatic aortic occlusive disease (47 patients), aortic aneurysmal disease (30 patients), and visceral atherosclerosis (13 patients). Transaortic endarterectomy was used for 67% of renal artery reconstructions and 69% of visceral arteries. Aortic reconstruction required prosthetic grafting in 74%. A standard transabdominal approach was used in 72 of 90 patients (80%), and thoraco-retroperitoneal exposure was necessary in 18 patients. Perioperative mortality was 9% (8/90) and morbidity 16% (14/90). Ninety per cent of the patients were evaluated at long-term (mean 32 months). Hypertension was cured or improved at discharge in 82% (59/72), and in 96% hypertension improvement was sustained during the follow-up interval. Renal function was improved or preserved in 93% (40/43) at discharge, and this response was sustained in 84% during the follow-up period. Late mortality (8/74, 11%) was lower than expected and is attributed to the technique of combined repair, the cure and control of hypertension, the prevention of ongoing renal ischemia, and the preservation of renal function. Images FIG. 1. FIGS. 2A and B. FIG. 3. FIG. 4. PMID:6465985

  18. Osteoprotegerin as a Marker of Atherosclerosis in Diabetic Patients

    PubMed Central

    Augoulea, Areti; Vrachnis, Nikolaos; Lambrinoudaki, Irene; Dafopoulos, Konstantinos; Iliodromiti, Zoe; Daniilidis, Angelos; Varras, Michail; Alexandrou, Andreas; Deligeoroglou, Efthymios; Creatsas, George

    2013-01-01

    Atherosclerosis is the principal cause of cardiovascular disease (CVD) and has many risk factors, among which is diabetes. Osteoprotegerin (OPG) is a soluble glycoprotein, involved in bone metabolism. OPG is also found in other tissues, and studies have shown that it is expressed in vascular smooth muscle cells. OPG has been implicated in various inflammations and also has been linked to diabetes mellitus. Increased serum OPG levels were found in patients with diabetes and poor glycemic control. Furthermore, prepubertal children with type 1 diabetes have significantly increased OPG levels. Receptor activator of nuclear factor kappa-B ligand (RANKL) is not found in the vasculature in normal conditions, but may appear in calcifying areas. OPG and RANKL are important regulators of mineral metabolism in both bone and vascular tissues. Few data are available on the relationship between plasma OPG/RANKL levels and endothelial dysfunction as assessed using noninvasive methods like ultrasound indexes, neither in the general population nor, more specifically, in diabetic patients. The aim of our review study was to investigate, based on the existing data, these interrelationships in order to identify a means of predicting, via noninvasive methods, later development of endothelial dysfunction and vascular complications in diabetic patients. PMID:23401681

  19. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

    PubMed

    Sanchez-Gaytan, Brenda L; Fay, Francois; Lobatto, Mark E; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E M; van Rijs, Sarian M; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J; Langer, Robert; Fayad, Zahi A; Mulder, Willem J M

    2015-03-18

    High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers. PMID:25650634

  20. Pentoxifylline Decreases Serum Level of Adhesion Molecules in Atherosclerosis Patients

    PubMed Central

    Mohammadpour, Amir Hooshang; Falsoleiman, Homa; Shamsara, Jamal; Abadi, Ghazaleh Allah; Rasooli, Ramin; Ramezani, Mohammad

    2014-01-01

    Background: Inflammation is involved in development, progression, and complications of atherosclerotic disease. Clinical studies have indicated that the level of monocyte chemoattractant protein 1 (MCP-1), IL-18, and adhesion molecules correlates with the severity of atherosclerosis and can predict future cardiovascular events. Experimental studies have shown pentoxifylline (PTX) reduces these factors in animal models. The purpose of the present pilot study was to evaluate effect of PTX on a group of inflammatory biomarkers in patients with coronary artery disease (CAD). Methods: Forty patients with angiographically documented CAD, who fulfilled inclusion and exclusion criteria, were entered in the double-blind, randomized, pilot clinical study. The patients were randomly given PTX (400 mg three times daily) or placebo (3 tab/day) for 2 months. Serum concentrations of MCP-1, IL-18, intercellular adhesion Molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured before and at the end of intervention by enzyme-linked immunosorbant assay. Results: Our study showed that the serum levels of ICAM-1 and VCAM-1 was decreased in the study population after two-month treatment (P<0.05). Conclusion: Based on the results of our pilot study, administration of PTX in CAD patients significantly decreases adhesion molecules levels. PMID:24375159

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

    PubMed

    Cheung, Yiu-Fai

    2014-11-01

    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

  2. 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

  3. Iron in arterial plaque: modifiable risk factor for atherosclerosis.

    PubMed

    Sullivan, Jerome L

    2009-07-01

    It has been proposed that iron depletion protects against cardiovascular disease. There is increasing evidence that one mechanism for this protection may involve a reduction in iron levels within atherosclerotic plaque. Large increases in iron concentration are seen in human atherosclerotic lesions in comparison to levels in healthy arterial tissue. In animal models, depletion of lesion iron levels in vivo by phlebotomy, systemic iron chelation treatment or dietary iron restriction reduces lesion size and/or increases plaque stability. A number of factors associated with increased arterial disease or increased cardiovascular events is also associated with increased plaque iron. In rats, infusion of angiotensin II increases ferritin levels and arterial thickness which are reversed by treatment with the iron chelator deferoxamine. In humans, a polymorphism for haptoglobin associated with increased cardiovascular disease is also characterized by increased lesional iron. Heme oxygenase 1 (HO1) is an important component of the system for mobilization of iron from macrophages. Human HO1 promoter polymorphisms causing weaker upregulation of the enzyme are associated with increased cardiovascular disease and increased serum ferritin. Increased cardiovascular disease associated with inflammation may be in part caused by elevated hepcidin levels that promote retention of iron within plaque macrophages. Defective retention of iron within arterial macrophages in genetic hemochromatosis may explain why there is little evidence of increased atherosclerosis in this disorder despite systemic iron overload. The reviewed findings support the concept that arterial plaque iron is a modifiable risk factor for atherogenesis. PMID:18619522

  4. Decreased Naive and Increased Memory CD4+ T Cells Are Associated with Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Olson, Nels C.; Doyle, Margaret F.; Jenny, Nancy Swords; Huber, Sally A.; Psaty, Bruce M.; Kronmal, Richard A.; Tracy, Russell P.

    2013-01-01

    Background Adaptive immunity has been implicated in atherosclerosis in animal models and small clinical studies. Whether chronic immune activation is associated with atherosclerosis in otherwise healthy individuals remains underexplored. We hypothesized that activation of adaptive immune responses, as reflected by higher proportions of circulating CD4+ memory cells and lower proportions of naive cells, would be associated with subclinical atherosclerosis. Methods and Findings We examined cross-sectional relationships of circulating CD4+ naive and memory T cells with biomarkers of inflammation, serologies, and subclinical atherosclerosis in 912 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Circulating CD4+ naive cells were higher in women than men and decreased with age (all p-values <0.0001). European-Americans had higher levels of naive cells and lower levels of memory cells compared with African-Americans and Hispanic-Americans (all p-values ?0.0005). Lower naive/higher memory cells were associated with interleukin-6 levels. In multivariate models, cytomegalovirus (CMV) and H. Pylori titers were strongly associated with higher memory and lower naive cells (all p-values <0.05). Higher memory cells were associated with coronary artery calcification (CAC) level in the overall population [?-Coefficient (95% confidence interval (CI)) ?=?0.20 (0.03, 0.37)]. Memory and naive (inversely) cells were associated with common carotid artery intimal media thickness (CC IMT) in European-Americans [memory: ??=? 0.02 (0.006, 0.04); naive: ??=??0.02 (?0.004, ?0.03)]. Conclusions These results demonstrate that the degree of chronic adaptive immune activation is associated with both CAC and CC IMT in otherwise healthy individuals, consistent with the known role of CD4+ T cells, and with innate immunity (inflammation), in atherosclerosis. These data are also consistent with the hypothesis that immunosenescence accelerates chronic diseases by putting a greater burden on the innate immune system, and suggest the importance of prospective studies and research into strategies to modulate adaptive immune activation in chronic disease states such as atherosclerosis. PMID:24009662

  5. High glucose downregulates the number of caveolae in monocytes through oxidative stress from NADPH oxidase: implications for atherosclerosis.

    PubMed

    Hayashi, Toshio; Juliet, Packiasamy A R; Miyazaki, Asaka; Ignarro, Louis J; Iguchi, Akihisa

    2007-03-01

    Atherosclerosis, an inflammatory disease, is closely associated with hyperglycemia, major sign of diabetes mellitus. Caveolae are vesicular invaginations of the plasma membrane that mediate the intracellular transport of lipids such as cholesterol. We evaluated the relationship between the expression of caveolin-1 and the number of caveolae in macrophages under conditions of high glucose concentration. Increased superoxide production, induction of inducible nitric oxide synthase (iNOS), and decreased caveolin-1 were observed in a concentration-dependent manner in THP-1 derived macrophages with high glucose concentrations. Mannitol, used as an osmotic control, showed no effects. Furthermore, co-localization of the NADPH oxidase component, p47(phox), and caveolin was confirmed by confocal microscopy. An atomic force microscopy (AFM) study showed that high glucose concentrations reduced the number and size of the caveolae. The percentage of cells with fragmented DNA was increased in cells grown in hyperglycemic media. Taken together, high glucose concentrations suppress the levels of caveolin-1 expression and reduce the number of caveolae. This might be due to the actions of superoxide via the activation of NADPH oxidase by translocation of its component and uncoupling of induced iNOS in macrophages. Furthermore, the apoptosis of macrophages might occur with high glucose concentrations, leading to the spreading of lipids from macrophages into intracellular spaces in the vessel wall. PMID:17240121

  6. 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.

  7. 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.

  8. Menstrual suppression: current perspectives

    PubMed Central

    Hillard, Paula Adams

    2014-01-01

    Menstrual suppression to provide relief of menstrual-related symptoms or to manage medical conditions associated with menstrual morbidity or menstrual exacerbation has been used clinically since the development of steroid hormonal therapies. Options range from the extended or continuous use of combined hormonal oral contraceptives, to the use of combined hormonal patches and rings, progestins given in a variety of formulations from intramuscular injection to oral therapies to intrauterine devices, and other agents such as gonadotropin-releasing hormone (GnRH) antagonists. The agents used for menstrual suppression have variable rates of success in inducing amenorrhea, but typically have increasing rates of amenorrhea over time. Therapy may be limited by side effects, most commonly irregular, unscheduled bleeding. These therapies can benefit women’s quality of life, and by stabilizing the hormonal milieu, potentially improve the course of underlying medical conditions such as diabetes or a seizure disorder. This review addresses situations in which menstrual suppression may be of benefit, and lists options which have been successful in inducing medical amenorrhea. PMID:25018654

  9. Leishmania major Self-Limited Infection Increases Blood Cholesterol and Promotes Atherosclerosis Development

    PubMed Central

    Fernandes, Luciana R.; Ribeiro, Ana Cecília C.; Segatto, Marcela; Santos, Luís Felipe F. F.; Amaral, Joana; Portugal, Luciane R.; Leite, Jacqueline I. A.

    2013-01-01

    Leishmania major infection of resistant mice causes a self-limited lesion characterized by macrophage activation and a Th1 proinflammatory response. Atherosclerosis is an inflammatory disease involving hypercholesterolemia and macrophage activation. In this study, we evaluated the influence of L. major infection on the development of atherosclerosis using atherosclerosis-susceptible apolipoprotein E-deficient (apoE KO) mice. After 6 weeks of infection, apoE KO mice exhibited reduced footpad swelling and parasitemia similar to C57BL/6 controls, confirming that both strains are resistant to infection with L. major. L. major-infected mice had increased plasma cholesterol levels and reduced triacylglycerols. With regard to atherosclerosis, noninfected mice developed only fatty streak lesions, while the infected mice presented with advanced lesions containing a necrotic core and an abundant inflammatory infiltrate. CD36 expression was increased in the aortic valve of the infected mice, indicating increased macrophage activation. In conclusion, L. major infection, although localized and self-limited in resistant apoE KO mice, has a detrimental effect on the blood lipid profile, increases the inflammatory cell migration to atherosclerotic lesions, and promotes atherogenesis. These effects are consequences of the stimulation of the immune system by L. major, which promotes the inflammatory components of atherosclerosis, which are primarily the parasite-activated macrophages. PMID:23710353

  10. Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature.

    PubMed

    Zhang, Linjie; Yang, Li

    2015-01-01

    Immune responses play an important role in the pathophysiology of atherosclerosis and ischemic stroke. Atherosclerosis is a common condition that increases the risk of stroke. Hyperlipidemia damages endothelial cells, thus initiating chemokine pathways and the release of inflammatory cytokines-this represents the first step in the inflammatory response to atherosclerosis. Blocking blood flow in the brain leads to ischemic stroke, and deprives neurons of oxygen and energy. Damaged neurons release danger-associated molecular patterns, which promote the activation of innate immune cells and the release of inflammatory cytokines. The nuclear factor ?-light-chain-enhancer of activated B cells ?B (NF-?B) pathway plays a key role in the pathogenesis of atherosclerosis and ischemic stroke. Vinpocetine is believed to be a potent anti-inflammatory agent and has been used to treat cerebrovascular disorders. Vinpocetine improves neuronal plasticity and reduces the release of inflammatory cytokines and chemokines from endothelial cells, vascular smooth muscle cells, macrophages, and microglia, by inhibiting the inhibitor of the NF-?B pathway. This review clarifies the anti-inflammatory role of vinpocetine in atherosclerosis and ischemic stroke. PMID:25549058

  11. Protection of salvianolate against atherosclerosis via regulating the inflammation in rats.

    PubMed

    Meng, Chun; Zhuo, Xiao-Qing; Xu, Guo-Hong; Liu, Jian-Li

    2014-10-01

    Inflammation plays an essential role in the pathophysiology of atherosclerosis. Our study was aimed to investigate whether salvianolate, a novel water-soluble phenolic compound of Danshen, alleviates atherosclerosis via regulating the inflammation in rats. High fat diet feeding plus vitamin D3 injection was used to induce atherosclerosis in rats. Salvianolate (60, 120 or 240 mg/kg) or placebo was given to atherosclerotic rats. The plasma lipids, interleukin 6 (IL-6) and C reactive protein (CRP) were measured by ELISA. CD4+CD25+Foxp3+ cells were determined by flow cytometry. Histological changes were examined by hematoxylin and eosin staining. The results showed that the levels of plasma IL-6 and CRP were elevated in the rats fed on high fat diet, and the histological analysis demonstrated the successful establishment of atherosclerosis models. Treatment with salvianolate alleviated the atherosclerotic process and decreased the levels of plasma IL-6 and CRP. Also the number of CD4+CD25+Foxp3+ cells was increased in salvianolate-treated rats. It was concluded that salvianolate could treat atherosclerosis via modulating the inflammation at cytokine and cell levels. PMID:25318872

  12. Signal transducer of inflammation gp130 modulates atherosclerosis in mice and man

    PubMed Central

    Luchtefeld, Maren; Schunkert, Heribert; Stoll, Monika; Selle, Tina; Lorier, Rachel; Grote, Karsten; Sagebiel, Christian; Jagavelu, Kumaravelu; Tietge, Uwe J.F.; Assmus, Ulrike; Streetz, Konrad; Hengstenberg, Christian; Fischer, Marcus; Mayer, Björn; Maresso, Karen; El Mokhtari, Nour Eddine; Schreiber, Stefan; Müller, Werner; Bavendiek, Udo; Grothusen, Christina; Drexler, Helmut; Trautwein, Christian; Broeckel, Ulrich; Schieffer, Bernhard

    2007-01-01

    Liver-derived acute phase proteins (APPs) emerged as powerful predictors of cardiovascular disease and cardiovascular events, but their functional role in atherosclerosis remains enigmatic. We report that the gp130 receptor, which is a key component of the inflammatory signaling pathway within hepatocytes, influences the risk of atherosclerosis in a hepatocyte-specific gp130 knockout. Mice on an atherosclerosis-prone genetic background exhibit less aortic atherosclerosis (P < 0.05) with decreased plaque macrophages (P < 0.01). Translating these findings into humans, we show that genetic variation within the human gp130 homologue, interleukin 6 signal transducer (IL6ST), is significantly associated with coronary artery disease (CAD; P < 0.05). We further show a significant association of atherosclerotic disease at the ostium of the coronary arteries (P < 0.005) as a clinically important and heritable subphenotype in a large sample of families with myocardial infarction (MI) and a second independent population–based cohort. Our results reveal a central role of a hepatocyte-specific, gp130-dependent acute phase reaction for plaque development in a murine model of atherosclerosis, and further implicate IL6ST as a genetic susceptibility factor for CAD and MI in humans. Thus, the acute phase reaction should be considered an important target for future drug development in the management of CAD. PMID:17664290

  13. A brief elevation of serum amyloid A is sufficient to increase atherosclerosis.

    PubMed

    Thompson, Joel C; Jayne, Colton; Thompson, Jennifer; Wilson, Patricia G; Yoder, Meghan H; Webb, Nancy; Tannock, Lisa R

    2015-02-01

    Serum amyloid A (SAA) has a number of proatherogenic effects including induction of vascular proteoglycans. Chronically elevated SAA was recently shown to increase atherosclerosis in mice. The purpose of this study was to determine whether a brief increase in SAA similarly increased atherosclerosis in a murine model. The recombination activating gene 1-deficient (rag1(-/-)) × apolipoprotein E-deficient (apoe(-/-)) and apoe(-/-) male mice were injected, multiple times or just once respectively, with an adenoviral vector encoding human SAA1 (ad-SAA); the injected mice and controls were maintained on chow for 12-16 weeks. Mice receiving multiple injections of ad-SAA, in which SAA elevation was sustained, had increased atherosclerosis compared with controls. Strikingly, mice receiving only a single injection of ad-SAA, in which SAA was only briefly elevated, also had increased atherosclerosis compared with controls. Using in vitro studies, we demonstrate that SAA treatment leads to increased LDL retention, and that prevention of transforming growth factor beta (TGF-?) signaling prevents SAA-induced increases in LDL retention and SAA-induced increases in vascular biglycan content. We propose that SAA increases atherosclerosis development via induction of TGF-?, increased vascular biglycan content, and increased LDL retention. These data suggest that even short-term inflammation with concomitant increase in SAA may increase the risk of developing CVD. PMID:25429103

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

    PubMed

    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

    2015-04-01

    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. PMID:25550469

  15. Regulatory role of mitochondria in oxidative stress and atherosclerosis

    PubMed Central

    Chang, Jui-Chih; Kou, Shou-Jen; Lin, Wei-Ting; Liu, Chin-San

    2010-01-01

    Mitochondrial physiology and biogenesis play a crucial role in the initiation and progression of cardiovascular disease following oxidative stress-induced damage such as atherosclerosis (AST). Dysfunctional mitochondria caused by an increase in mitochondrial reactive oxygen species (ROS) production, accumulation of mitochondrial DNA damage, and respiratory chain deficiency induces death of endothelial/smooth muscle cells and favors plaque formation/rupture via the regulation of mitochondrial biogenesis-related genes such as peroxisome proliferator-activated receptor ? coactivator (PGC-1), although more detailed mechanisms still need further study. Based on the effect of healthy mitochondria produced by mitochondrial biogenesis on decreasing ROS-mediated cell death and the recent finding that the regulation of PGC-1 involves mitochondrial fusion-related protein (mitofusin), we thus infer the regulatory role of mitochondrial fusion/fission balance in AST pathophysiology. In this review, the first section discusses the possible association between AST-inducing factors and the molecular regulatory mechanisms of mitochondrial biogenesis and dynamics, and explains the role of mitochondria-dependent regulation in cell apoptosis during AST development. Furthermore, nitric oxide has the Janus-faced effect by protecting vascular damage caused by AST while being a reactive nitrogen species (RNS) which act together with ROS to damage cells. Therefore, in the second section we discuss mitochondrial ATP-sensitive K+ channels, which regulate mitochondrial ion transport to maintain mitochondrial physiology, involved in the regulation of ROS/RNS production and their influence on AST/cardiovascular diseases (CVD). Through this review, we can further appreciate the multi-regulatory functions of the mitochondria involved in AST development. The understanding of these related mechanisms will benefit drug development in treating AST/CVD through targeted biofunctions of mitochondria. PMID:21160733

  16. Quantifying progression and regression of thrombotic risk in experimental atherosclerosis.

    PubMed

    Palekar, Rohun U; Jallouk, Andrew P; Goette, Matthew J; Chen, Junjie; Myerson, Jacob W; Allen, John S; Akk, Antonina; Yang, Lihua; Tu, Yizheng; Miller, Mark J; Pham, Christine T N; Wickline, Samuel A; Pan, Hua

    2015-07-01

    Currently, there are no generally applicable noninvasive methods for defining the relationship between atherosclerotic vascular damage and risk of focal thrombosis. Herein, we demonstrate methods to delineate the progression and regression of vascular damage in response to an atherogenic diet by quantifying the in vivo accumulation of semipermeable 200-300 nm perfluorocarbon core nanoparticles (PFC-NP) in ApoE null mouse plaques with [(19)F] magnetic resonance spectroscopy (MRS). Permeability to PFC-NP remained minimal until 12 weeks on diet, then increased rapidly following 12 weeks, but regressed to baseline within 8 weeks after diet normalization. Markedly accelerated clotting (53.3% decrease in clotting time) was observed in carotid artery preparations of fat-fed mice subjected to photochemical injury as defined by the time to flow cessation. For all mice on and off diet, an inverse linear relationship was observed between the permeability to PFC-NP and accelerated thrombosis (P = 0.02). Translational feasibility for quantifying plaque permeability and vascular damage in vivo was demonstrated with clinical 3 T MRI of PFC-NP accumulating in plaques of atherosclerotic rabbits. These observations suggest that excessive permeability to PFC-NP may indicate prothrombotic risk in damaged atherosclerotic vasculature, which resolves within weeks after dietary therapy.-Palekar, R. U., Jallouk, A. P., Goette, M. J., Chen, J., Myerson, J. W., Allen, J. S., Akk, A., Yang, L., Tu, Y., Miller, M. J., Pham, C. T. N., Wickline, S. A., Pan, H. Quantifying progression and regression of thrombotic risk in experimental atherosclerosis. PMID:25857553

  17. Fluorescence spectroscopic detection of early injury-induced atherosclerosis

    NASA Astrophysics Data System (ADS)

    Lucas, Alexandra; Perk, Masis; Wen, Yue; Smith, Carol

    1992-08-01

    Laser-induced fluorescence spectroscopy has been used for the detection of advanced atherosclerotic lesions. Angioplasty balloon-mediated injury was examined spectroscopically in order to assess the sensitivity of fluorescence spectroscopy for detection of early atherosclerosis. Abdominal aortic balloon angioplasty was performed via femoral artery cutdown in nine White Leghorn roosters (five normal, four atherogenic diet). Roosters were sacrificed at 1, 2, 4, 8, and 12 week intervals. Fluorescence emission spectra (n equals 114) were recorded from each aortic section (XeCl excimer laser, 308 nm, 1.5 - 2.0 mJ/pulse, 5 Hz). Changes in normalized fluorescence emission intensity were correlated with selected sections of histology. All balloon-injured segments showed intimal fibrous proliferation. For intimal thickness measuring > 70 (mu) , fluorescence emission intensity was decreased at 440 - 460 nm (p < 0.0005). Lesions complicated by thrombus also had lower fluorescence emission at 425 - 450 nm when compared to histologically normal aorta (p < 0.009). In injured segments high cholesterol diet resulted in lower recorded fluorescence emission at 440 - 460 nm (p < 0.001) associated with the increase in intimal thickness. Spectra from uninjured elastic aorta (aortic arch and thoracic aorta) had greater fluorescence intensity at 380 - 445 nm than muscular (abdominal) aorta (p < 0.01), therefore, only spectra from injured and uninjured segments of corresponding areas of the aorta were compared. The conclusion is: (1) Early intimal proliferative changes after angioplasty can be detected by fluorescence spectroscopy. (2) Spectra from elastic thoracic aorta differ significantly from the spectra of muscular abdominal aorta.

  18. Implitapide, a microsomal triglyceride transfer protein inhibitor, reduces progression of atherosclerosis in apolipoprotein E knockout mice fed a Western-type diet: involvement of the inhibition of postprandial triglyceride elevation.

    PubMed

    Ueshima, Koji; Akihisa-Umeno, Hitomi; Nagayoshi, Akira; Takakura, Shoji; Matsuo, Masahiko; Mutoh, Seitaro

    2005-02-01

    Microsomal triglyceride transfer protein (MTP) is essential for the synthesis of both chylomicron in the intestine and very low-density lipoprotein in the liver. An MTP inhibitor, (2S)-2-cyclopentyl-2-[4-[(2,4-dimethyl-9H-pyrido[2,3-b]indol-9-yl)methyl]phenyl]-N-[(1S)-2-hydroxy-1-phenylethyl]ethanamide (implitapide), has been shown to suppress atherosclerosis in apolipoprotein E knockout (apoE KO) mice. To elucidate the antiatherosclerotic mechanisms of implitapide in the mice, we examined the effects on plasma lipid levels, triglyceride (TG) elevation after oral fat loading, and development of atherosclerosis in apoE KO mice fed a Western-type diet. Implitapide at a dosage of approximately 3.2 mg/kg/day significantly reduced both total cholesterol and TG levels during the 8-week treatment period. In addition, implitapide significantly inhibited the increase in plasma TG levels after oral olive oil loading tests conducted after 4 weeks of treatment. After the treatment, implitapide significantly suppressed the atherosclerotic lesion area by 83% compared with a control group. These results provide direct evidence that the antiatherosclerotic effects of implitapide in apoE KO mice are associated with the inhibition of postprandial TG elevation, in addition to the reduction of both plasma total cholesterol and TG levels. PMID:15684478

  19. Optical imaging innovations for atherosclerosis research: multiphoton microscopy and optical nanoscopy.

    PubMed

    Megens, Remco T A; Bianchini, Mariaelvy; Schmitt, Martin M N; Weber, Christian

    2015-06-01

    Cardiovascular disease is the leading cause of death and morbidity worldwide. Improving vascular prevention and therapy based on a refined mechanistic pervasion of atherosclerosis as the underlying pathology could limit the effect of vascular disease in aging societies. During the past decades, microscopy has contributed greatly to a better understanding of vascular physiology and pathology by allowing imaging of living specimen with subcellular resolution and high specificity. An important advance has been accomplished through the application of multiphoton microscopy in the vascular domain, a technological development that enabled multidimensional and dynamic imaging deep into the cellular architecture of intact tissue under physiological conditions. To identify and validate new targets for treating atherosclerosis, novel imaging strategies with nanoscale resolution will be essential to visualize molecular processes in intracellular and extracellular compartments. This review will discuss the current use of 2-photon microscopy and will provide an overview and outlook on options for introducing nanoscopic optical imaging modalities in atherosclerosis research. PMID:25908769

  20. 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

  1. Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease

    PubMed Central

    Otani, Hajime

    2013-01-01

    Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD) in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR) and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span. PMID:23738041

  2. Iron and atherosclerosis: nailing down a novel target with magnetic resonance.

    PubMed

    Sharkey-Toppen, Travis P; Tewari, Arun K; Raman, Subha V

    2014-07-01

    Iron is an essential mineral in many proteins and enzymes in human physiology, with limited means of iron elimination to maintain iron balance. Iron accrual incurs various pathological mechanisms linked to cardiovascular disease. In atherosclerosis, iron catalyzes the creation of reactive oxygen free radicals that contribute to lipid modification, which is essential to atheroma formation. Inflammation further fuels iron-related pathologic processes associated with plaque progression. Given iron's role in atherosclerosis development, in vivo detection techniques sensitive iron are needed for translational studies targeting iron for earlier diagnosis and treatment. Magnetic resonance imaging is uniquely able to quantify iron in human tissues noninvasively and without ionizing radiation, offering appealing for longitudinal and interventional studies. Particularly intriguing is iron's complementary biology vs. calcium, which is readily detectable by computed tomography. This review summarizes the role of iron in atherosclerosis with considerable implications for novel diagnostic and therapeutic approaches. PMID:24590608

  3. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2.

    PubMed

    Furuhashi, Masato; Tuncman, Gürol; Görgün, Cem Z; Makowski, Liza; Atsumi, Genichi; Vaillancourt, Eric; Kono, Keita; Babaev, Vladimir R; Fazio, Sergio; Linton, MacRae F; Sulsky, Richard; Robl, Jeffrey A; Parker, Rex A; Hotamisligil, Gökhan S

    2007-06-21

    Adipocyte fatty-acid-binding protein, aP2 (FABP4) is expressed in adipocytes and macrophages, and integrates inflammatory and metabolic responses. Studies in aP2-deficient mice have shown that this lipid chaperone has a significant role in several aspects of metabolic syndrome, including type 2 diabetes and atherosclerosis. Here we demonstrate that an orally active small-molecule inhibitor of aP2 is an effective therapeutic agent against severe atherosclerosis and type 2 diabetes in mouse models. In macrophage and adipocyte cell lines with or without aP2, we also show the target specificity of this chemical intervention and its mechanisms of action on metabolic and inflammatory pathways. Our findings demonstrate that targeting aP2 with small-molecule inhibitors is possible and can lead to a new class of powerful therapeutic agents to prevent and treat metabolic diseases such as type 2 diabetes and atherosclerosis. PMID:17554340

  4. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2

    PubMed Central

    Furuhashi, Masato; Tuncman, Gürol; Görgün, Cem Z.; Makowski, Liza; Atsumi, Genichi; Vaillancourt, Eric; Kono, Keita; Babaev, Vladimir R.; Fazio, Sergio; Linton, MacRae F.; Sulsky, Richard; Robl, Jeffrey A.; Parker, Rex A.; Hotamisligil, Gökhan S.

    2014-01-01

    Adipocyte fatty-acid-binding protein, aP2 (FABP4) is expressed in adipocytes and macrophages, and integrates inflammatory and metabolic responses. Studies in aP2-deficient mice have shown that this lipid chaperone has a significant role in several aspects of metabolic syndrome, including type 2 diabetes and atherosclerosis. Here we demonstrate that an orally active small-molecule inhibitor of aP2 is an effective therapeutic agent against severe atherosclerosis and type 2 diabetes in mouse models. In macrophage and adipocyte cell lines with or without aP2, we also show the target specificity of this chemical intervention and its mechanisms of action on metabolic and inflammatory pathways. Our findings demonstrate that targeting aP2 with small-molecule inhibitors is possible and can lead to a new class of powerful therapeutic agents to prevent and treat metabolic diseases such as type 2 diabetes and atherosclerosis. PMID:17554340

  5. Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP

    PubMed Central

    Zhao, Xiaoqi; Liu, Yuzhou; Zhong, Yucheng; Liu, Bo; Yu, Kunwu; Shi, Huairui; Zhu, Ruirui; Meng, Kai; Zhang, Wei; Wu, Bangwei

    2015-01-01

    Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-?. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-? in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE?/? mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-?1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells.

  6. Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis

    Microsoft Academic Search

    Mark R Adams; Jacqui Robinson; Robyn McCredie; J. Paul Seale; Keld E Sorensen; John E Deanfield; David S Celermajer

    1998-01-01

    Objectives. We sought to assess smooth muscle function in adults at risk for atherosclerosis.Background. Previous studies in subjects at risk for atherosclerosis have demonstrated arterial endothelial dysfunction, with reduced vasodilator responses after pharmacologic or physiologic stimulation of endothelial nitric oxide (NO). Most have also shown a slight but nonsignificant impairment of vasodilation in response to exogenous sources of NO, such

  7. 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...

  8. 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

  9. Genetic?Genomic Replication to Identify Candidate Mouse Atherosclerosis Modifier Genes

    PubMed Central

    Hsu, Jeffrey; Smith, Jonathan D.

    2013-01-01

    Objective Genetics plays a large role in atherosclerosis susceptibility in humans and mice. We attempted to confirm previously determined mouse atherosclerosis?associated loci and use bioinformatics and transcriptomics to create a catalog of candidate atherosclerosis modifier genes at these loci. Methods and Results A strain intercross was performed between AKR and DBA/2 mice on the apoE?/? background generating 166 F2 progeny. Using the phenotype log10 of the aortic root lesion area, we identified 3 suggestive atherosclerosis quantitative trait loci (Ath QTLs). When combined with our prior strain intercross, we confirmed 3 significant Ath QTLs on chromosomes 2, 15, and 17, with combined logarithm of odds scores of 5.9, 5.3, and 5.6, respectively, which each met the genome?wide 5% false discovery rate threshold. We identified all of the protein coding differences between these 2 mouse strains within the Ath QTL intervals. Microarray gene expression profiling was performed on macrophages and endothelial cells from this intercross to identify expression QTLs (eQTLs), the loci that are associated with variation in the expression levels of specific transcripts. Cross tissue eQTLs and macrophage eQTLs that replicated from a prior strain intercross were identified. These bioinformatic and eQTL analyses produced a comprehensive list of candidate genes that may be responsible for the Ath QTLs. Conclusions Replication studies for clinical traits as well as gene expression traits are worthwhile in identifying true versus false genetic associations. We have replicated 3 loci on mouse chromosomes 2, 15, and 17 that are associated with atherosclerosis. We have also identified protein coding differences and multiple replicated eQTLs, which may be useful in the identification of atherosclerosis modifier genes. PMID:23525445

  10. Monocyte Angiotensin Converting Enzyme Expression May Be Associated with Atherosclerosis Rather than Arteriosclerosis in Hemodialysis Patients

    PubMed Central

    Ulrich, Christof; Seibert, Eric; Heine, Gunnar H.; Fliser, Danilo

    2011-01-01

    Summary Background and objectives Circulating monocytes can be divided into functionally distinct subpopulations according to their surface expression of CD14 and CD16. Monocytes with high-level expression of both antigens (CD14++CD16+, Mo2 cells) are associated with cardiovascular morbidity and mortality in hemodialysis patients. These cells express angiotensin converting enzyme (ACE) on their surface. They are involved in the association of chronic inflammation and cardiovascular disease in kidney patients. Cardiovascular morbidity results from atherosclerosis (plaque-forming, vessel occluding disease) and arteriosclerosis (loss of arterial dampening function). It is unknown whether ACE-expressing proinflammatory monocytes are related to atherosclerosis, arteriosclerosis, or both. Design, setting, participants, & measurements During baseline examination for a prospective study on monocyte ACE expression and mortality, 60 chronic hemodialysis patients of an academic outpatient center were screened for atherosclerosis by carotid artery ultrasound, for arteriosclerosis by pulse pressure measurement, and for ACE expression on Mo2 cells by flow cytometry. Results ACE expression on Mo2 monocytes was significantly higher in patients with severe compared with those with little or no carotid atherosclerosis. Mo2 ACE correlated with a score to semiquantify atherosclerosis and remained a significant predictor of carotid plaques in multivariate analysis including the other univariately associated variables of age, hemoglobin A1c, and albumin. Mo2 ACE was not related to pulse pressure. Conclusions ACE expression on Mo2, although being a known predictor of mortality and cardiovascular disease in end-stage renal disease patients, may act via enhancement of atherosclerosis rather than arteriosclerosis. PMID:21127137

  11. The 9p21 susceptibility locus for coronary artery disease and the severity of coronary atherosclerosis

    PubMed Central

    Chen, Suet Nee; Ballantyne, Christie M; Gotto, Antonio M; Marian, Ali J

    2009-01-01

    Background Case-control Genome-Wide Association Studies (GWAS) have identified single nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). The locus does not contain a clear candidate gene. Hence, the results of GWAS have raised an intense interest in delineating the basis for the observed association. We analyzed association of 4 SNPs at the 9p21 locus with the severity and progression of coronary atherosclerosis, as determined by serial quantitative coronary angiograms (QCA) in the well-characterized Lipoprotein Coronary Atherosclerosis Study (LCAS) population. The LCAS is a randomized placebo-control longitudinal follow-up study in patients with CAD conducted to test the effects of fluvastatin on progression or regression of coronary atherosclerosis. Methods Extensive plasma lipid levels were measured at the baseline and 2 1/2 years after randomization. Likewise serial QCA was performed at the baseline and upon completion of the study. We genotyped the population for 4 SNPs, previously identified as the susceptibility SNPs for CAD in GWAS, using fluorogenic 5' nuclease assays. We reconstructed the haplotypes using Phase 2, analyzed SNP and haplotype effects using the Thesias software as well as by the conventional statistical methods. Results Only Caucasians were included since they comprised 90% of the study population (332/371 with available DNA sample). The 4 SNPs at the 9p21 locus were in tight linkage disequilibrium, leading to 3 common haplotypes in the LCAS population. We found no significant association between quantitative indices of severity of coronary atherosclerosis, such as minimal lumen diameter and number of coronary lesions or occlusions and the 9p21 SNPs and haplotypes. Likewise, there was no association between quantitative indices of progression of coronary atherosclerosis and the SNPs or haplotypes. Similarly, we found no significant SNP or haplotype effect on severity and progression of coronary atherosclerosis. Conclusion We conclude the 4 SNPs at the 9p21 locus analyzed in this study do not impart major effects on the severity or progression of coronary atherosclerosis. The effect size may be very modest or the observed association of the CAD with SNPs at the 9p21 locus in the case-control GWAS reflect involvement of vascular mechanisms not directly related to the severity or progression of coronary atherosclerosis. PMID:19173706

  12. Unihemispheric Burst Suppression

    PubMed Central

    Villemarette-Pittman, Nicole R.; Rogers, Cornel T.; Torres-Delgado, Frank; Olejniczak, Piotr W.; England, John D.

    2014-01-01

    Burst suppression (BS) consists of bursts of high-voltage slow and sharp wave activity alternating with periods of background suppression in the electroencephalogram (EEG). When induced by deep anesthesia or encephalopathy, BS is bihemispheric and is often viewed as a non-epileptic phenomenon. In contrast, unihemispheric BS is rare and its clinical significance is poorly understood. We describe here two cases of unihemispheric BS. The first patient is a 56-year-old woman with a left temporoparietal tumor who presented in convulsive status epilepticus. EEG showed left hemispheric BS after clinical seizure termination with lorazepam and propofol. The second patient is a 39-year-old woman with multiple medical problems and a vague history of seizures. After abdominal surgery, she experienced a convulsive seizure prompting treatment with propofol. Her EEG also showed left hemispheric BS. In both cases, increasing the propofol infusion rate resulted in disappearance of unihemispheric BS and clinical improvement. The prevailing view that typical bihemispheric BS is non-epileptic should not be extrapolated automatically to unihemispheric BS. The fact that unihemispheric BS was associated with clinical seizure and resolved with propofol suggests that, in both cases, an epileptic mechanism was responsible for unihemispheric BS. PMID:25309713

  13. Beneficial effects of a novel IH636 grape seed proanthocyanidin extract and a niacin-bound chromium in a hamster atherosclerosis model

    Microsoft Academic Search

    J. A. Vinson; M. A. Mandarano; D. L. Shuta; M. Bagchi; D. Bagchi

    2002-01-01

    Atherosclerosis is a disease of the arteries in which fatty plaques develop on the inner arterial wall, which eventually obstructs blood flow. Identified risk factors for atherosclerosis include genetics, diet, lifestyle, smoking, circulating lipid and cholesterol levels, and molecular and circulating signals of chronic vascular inflammation. The link between flavonoids and atherosclerosis is based partly on the evidence that some

  14. Quantum dot mediated imaging of atherosclerosis This article has been downloaded from IOPscience. Please scroll down to see the full text article.

    E-print Network

    Quantum dot mediated imaging of atherosclerosis This article has been downloaded from IOPscience of atherosclerosis Ashwath Jayagopal1,3 , Yan Ru Su2,3 , John L Blakemore2 , MacRae F Linton2 , Sergio Fazio2 Published 31 March 2009 Online at stacks.iop.org/Nano/20/165102 Abstract The progression of atherosclerosis

  15. Sex differences in the combined effect of chronic stress with impaired vascular endothelium functioning and the development of early atherosclerosis: The Cardiovascular Risk in Young Finns study

    Microsoft Academic Search

    Nadja Chumaeva; Mirka Hintsanen; Markus Juonala; Olli T Raitakari; Liisa Keltikangas-Järvinen

    2010-01-01

    BACKGROUND: The syndrome of vital exhaustion (VE), characterized by fatigue and irritability, may contribute to an increased risk of atherosclerosis. The aim of the study was to explore sex differences in the interactions of VE with endothelial dysfunction and VE with reduced carotid elasticity, the important contributors to the development of early atherosclerosis, on preclinical atherosclerosis. METHODS: The participants were

  16. Risk factors for accelerated atherosclerosis in young women with hyperprolactinemia.

    PubMed

    Medic-Stojanoska, Milica; Icin, Tijana; Pletikosic, Ivana; Bajkin, Ivana; Novakovic-Paro, Jovanka; Stokic, Edita; Spasic, Dragan T; Kovacev-Zavisic, Branka; Abenavoli, Ludovico

    2015-04-01

    Prolactin is a metabolic hormone. The hypothesis is that hyperprolactinemia can cause metabolic and inflammatory changes which are associated with accelerated atherosclerotic process, but the treatment of hyperprolactinemia with dopamine agonists, leads to reversibility of these processes. The first aim of this study was to determine whether hyperprolactinemia in premenopausal women is accompanied with the increase in body mass index (BMI), changes in body composition, lipid disturbances, the presence of inflammation and changes in systolic and diastolic blood pressure as risk factors for the development of early atherosclerosis. The second aim was to know whether the therapy of hyperprolactinemia and prolactin normalization lead to improvement of the observed parameters. Twenty female patients with prolactinomas, before and during treatment with dopamine agonists and 16 healthy controls were evaluated. Prolactin, BMI, total body fat, free fat mass, total body water, total cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) and fibrinogen as well as systolic and diastolic blood pressure were measured at baseline and during the therapy. Hyperprolactinemic patients had pathologic and significantly higher levels of prolactin (PRL) than the controls (p=0.000). The BMI, body fat, total body water (TBW), total cholesterol, triglycerides, LDL were in normal range and higher in the patients than in the controls. HDL was lower in hyperprolactinemic females than controls. The difference was significant only for body fat (fat % p=0.006; fat kg p=0.009). Fibrinogen was slightly increased in patients compared with the controls. Hyperprolactinemic patients had normal, but increased levels of systolic and diastolic blood pressure compared with the controls. The difference with border significance was found in diastolic blood pressure (p=0.065). The correlation of PRL with all the observed parameters was positive apart from HDL, but relatively significant only with diastolic blood pressure (r=0.31). The therapy with dopamine agonists caused the decrease of all the observed parameters, but significant decreases was achieved only in BMI (p=0.028), total cholesterol levels (p<0.001) and LDL (p<0.002). Changes in BMI, body composition, serum lipids and lipoproteins, fibrinogen level and blood pressure confirm our hypothesis about the possible role of hyperprolactinemia in developing adverse metabolic disturbances which are reversible after treatment. PMID:25649851

  17. T-Cell Phenotypes, Apoptosis and Inflammation in HIV+ Patients on Virologically Effective cART with Early Atherosclerosis

    PubMed Central

    Suardi, Elisa; Barassi, Alessandra; Cerrone, Maddalena; Martínez, Javier Sánchez; Bai, Francesca; D’Eril, Gian Vico Melzi; Monforte, Antonella D’Arminio; Marchetti, Giulia

    2012-01-01

    Objective We investigated the potential relationship between T-cell phenotype, inflammation, endotoxemia, and atherosclerosis evaluated by carotid intima-media thickness (IMT) in a cohort of HIV-positive patients undergoing long-term virologically suppressive combination antiretroviral therapy (cART). Design We studied 163 patients receiving virologically suppressive cART. Methods We measured IMT (carotid ultrasound); CD4+/CD8+ T-cell activation (CD38, CD45R0), differentiation (CD127), apoptosis (CD95), and senescence (CD28, CD57) (flow cytometry); plasma sCD14, IL-6, TNF- ?, sVCAM-1, hs-CRP, anti-CMV IgG (ELISA); LPS (LAL). The results were compared by Mann-Whitney, Kruskal-Wallis or Chi-square tests, and factors associated with IMT were evaluated by multivariable logistic regression. Results Of 163 patients, 112 demonstrated normal IMT (nIMT), whereas 51 (31.3%) had pathological IMT (pIMT: ?1 mm). Of the patients with pIMT, 22 demonstrated an increased IMT (iIMT), and 29 were shown to have plaques. These patient groups had comparable nadir and current CD4+, VLs and total length of time on cART. Despite similar proportions of CD38-expressing CD8+ cells (p?=?.95), pIMT patients exhibited higher activated memory CD8+CD38+CD45R0+ cells (p?=?.038) and apoptotic CD4+CD95+ (p?=?.01) and CD8+CD95+ cells (p?=?.003). In comparison to nIMT patients, iIMT patients tended to have lower numbers of early differentiated CD28+CD57? memory CD4+ (p?=?.048) and CD28–CD57?CD8+ cells (p?=?.006), both of which are associated with a higher proliferative potential. Despite no differences in plasma LPS levels, pIMT patients showed significantly higher circulating levels of sCD14 than did nIMT patients (p?=?.046). No differences in anti-CMV IgG was shown. Although circulating levels of sCD14 seemed to be associated with a risk of ATS in an unadjusted analysis, this effect was lost after adjusting for classical cardiovascular predictors. Conclusions Despite the provision of full viral suppression by cART, a hyperactivated, pro-apoptotic T-cell profile characterizes HIV-infected patients with early vascular damage, for whom the potential contribution of subclinical endotoxemia and anti-CMV immunity should be investigated further. PMID:23029393

  18. Ultraviolet-Visible and Fluorescence Spectroscopy Techniques Are Important Diagnostic Tools during the Progression of Atherosclerosis: Diet Zinc Supplementation Retarded or Delayed Atherosclerosis

    PubMed Central

    Abdelhalim, Mohamed Anwar K.; Moussa, Sherif A. Abdelmottaleb; AL-Mohy, Yanallah Hussain

    2013-01-01

    Background. In this study, we examined whether UV-visible and fluorescence spectroscopy techniques detect the progression of atherosclerosis in serum of rabbits fed on high-cholesterol diet (HCD) and HCD supplemented with zinc (HCD + Zn) compared with the control. Methods. The control rabbits group was fed on 100?g/day of normal diet. The HCD group was fed on Purina Certified Rabbit Chow supplemented with 1.0% cholesterol plus 1.0% olive oil (100?g/day) for the same period. The HCD + Zn group was fed on normal Purina Certified Rabbit Chow plus 1.0% cholesterol and 1.0% olive oil supplemented with 470?ppm Zn for the same feeding period. UV-visible and fluorescence spectroscopy and biochemistry in Rabbit's blood serum and blood hematology were measured in Rabbit's blood. Results. We found that the fluorescent peak of HCD shifted toward UV-visible wavelength compared with the control using fluorescent excitation of serum at 192?nm. In addition, they showed that supplementation of zinc (350?ppm) restored the fluorescent peak closely to the control. By using UV-visible spectroscopy approach, we found that the peak absorbance of HCD (about 280?nm) was higher than that of control and that zinc supplementation seemed to decrease the absorbance. Conclusions. This study demonstrates that ultraviolet-visible and fluorescence spectroscopy techniques can be applied as noninvasive techniques on a sample blood serum for diagnosing or detecting the progression of atherosclerosis. The Zn supplementation to rabbits fed on HCD delays or retards the progression of atherosclerosis. Inducing anemia in rabbits fed on HCD delays the progression of atherosclerosis. PMID:24350281

  19. Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis

    Microsoft Academic Search

    J. T. Salonen; K. Nyyssonen; R. Salonen; H.-M. Lakka; J. Kaikkonen; E. Porkkala-Sarataho; S. Voutilainen; T. A. Lakka; T. Rissanen; L. Leskinen; T.-P. Tuomainen; V.-P. Valkonen; U. Ristonmaa; H. E. Poulsen

    2000-01-01

    Abstract. Salonen JT, Nyysso ¨nen K, Salonen R, Lakka H-M, Kaikkonen J, Porkkala-Sarataho E, Voutilainen S, Lakka TA, Rissanen T, Leskinen L, tuomainen T-P, Valkonen V-P, Ristonmaa U (University of Kuopio, Finland), Poulsen HE (University of Copenhagen, Copenhagen, Denmark). Antioxidant Supplementa- tion in Atherosclerosis Prevention (ASAP) study: a randomized,trial of the effect of vitamins E and C on 3- year

  20. Association between Obesity, hsCRP ?2 mg/L, and Subclinical Atherosclerosis: Implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Blaha, Michael J.; Rivera, Juan J.; Budoff, Matthew J.; Blankstein, Ron; Agatston, Arthur; O’Leary, Daniel H.; Cushman, Mary; Lakoski, Susan; Criqui, Michael H.; Szklo, Moyses; Blumenthal, Roger S.; Nasir, Khurram

    2011-01-01

    Objective High-sensitivity C-reactive protein (hsCRP) levels are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The JUPITER trial has encouraged using hsCRP ?2 mg/L to guide statin therapy; however the association of hsCRP to atherosclerosis, independent of obesity, remains unknown. Methods and Results We studied 6,760 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were stratified into 4 groups: non-obese/low hsCRP, non-obese/high hsCRP, obese/low hsCRP, and obese/high hsCRP. Using multivariable logistic and robust linear regression, we described the association with subclinical atherosclerosis, using coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). Mean BMI was 28.3 ± 5.5 kg/m2, and median hsCRP was 1.9 mg/L (0.84 – 4.26). High hsCRP, in the absence of obesity, was not associated with CAC and was mildly associated with cIMT. Obesity was strongly associated with CAC and cIMT independent of hsCRP. When obesity and high hsCRP were both present, there was no evidence of multiplicative interaction. Similar associations were seen among 2,083 JUPITER-eligible individuals. Conclusions High hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with cIMT in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independent of hsCRP status. PMID:21474823

  1. Interference suppression of SRS

    SciTech Connect

    Kochanov, V P [V.E. Zuev Institute of Atmospheric Optics, Siberian Branch, Russian Academy of Sciences, Tomsk (Russian Federation)

    2011-01-24

    The theory of three-wave SRS is developed, which takes into account nonlinear dispersion of a medium for arbitrary phases of the pump waves at the input to the medium. The effect of interference suppression of SRS is predicted for values of the total phase of the three-wave pump (2n+1){pi} (n=0, {+-}1, {+-}2...), the effect being caused by the destructive interference of polarisations of the nonresonant dipole-allowed transitions. The relation between the contributions of the linear and nonlinear dispersions to the SRS is found. It is shown that at a sufficiently large wave detuning, the anti-Stokes wave amplitude experiences spatial oscillations. (nonlinear-optics phenomena)

  2. Ultrasonic Frost Suppression

    NASA Astrophysics Data System (ADS)

    Adachi, Kazunari; Saiki, Kazushi; Sato, Hiroki; Ito, Takahiro

    2003-02-01

    The authors have observed the accumulation of frost on the surface of a rectangular aluminum alloy (duralumin) plate flexurally vibrating at approximately 37 kHz in an atmosphere of almost 100% relative humidity at 2°C. The plate surface, which had been prepolished with abrasive slurry for maintaining its average surface roughness of about 100 nm, was refrigerated at a temperature of -20°C with cold carbon-dioxide gas as coolant. Experiments have been conducted with and without fine silver oxide powder spread on the plate surface so as to examine the effect of artificial ice crystal nuclei. Ultrasonic vibrations with an amplitude of 3.4 ?m (rms) are found to suppress frost accumulation by approximately 60%. The phenomenon cannot be ascribed directly to the heat generation caused by high-amplitude vibration, but may have a complex mechanical and/or acoustical effect on small ice crystals.

  3. 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.

  4. 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.

  5. Tomatidine, a tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in apoE-deficient mice by inhibiting acyl-CoA:cholesterol acyl-transferase (ACAT).

    PubMed

    Fujiwara, Yukio; Kiyota, Naoko; Tsurushima, Keiichiro; Yoshitomi, Makiko; Horlad, Hasita; Ikeda, Tsuyoshi; Nohara, Toshihiro; Takeya, Motohiro; Nagai, Ryoji

    2012-03-14

    It was previously revealed that esculeoside A, a new glycoalkaloid, and esculeogenin A, a new aglycon of esculeoside A, contained in ripe tomato ameliorate atherosclerosis in apoE-deficent mice. This study examined whether tomatidine, the aglycone of tomatine, which is a major tomato glycoalkaloid, also shows similar inhibitory effects on cholesterol ester (CE) accumulation in human monocyte-derived macrophages (HMDM) and atherogenesis in apoE-deficient mice. Tomatidine significantly inhibited the CE accumulation induced by acetylated LDL in HMDM in a dose-dependent manner. Tomatidine also inhibited CE formation in Chinese hamster ovary cells overexpressing acyl-CoA:cholesterol acyl-transferase (ACAT)-1 or ACAT-2, suggesting that tomatidine suppresses both ACAT-1 and ACAT-2 activities. Furthermore, the oral administration of tomatidine to apoE-deficient mice significantly reduced levels of serum cholesterol, LDL-cholesterol, and areas of atherosclerotic lesions. The study provides the first evidence that tomatidine significantly suppresses the activity of ACAT and leads to reduction of atherogenesis. PMID:22224814

  6. Endothelial-Specific Overexpression of Caveolin-1 Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice

    PubMed Central

    Fernández-Hernando, Carlos; Yu, Jun; Dávalos, Alberto; Prendergast, Jay; Sessa, William C.

    2010-01-01

    Caveolin-1 (Cav-1) is the major structural protein essential to the formation of the caveolae in endothelial cells. Genetic ablation of Cav-1 on an apolipoprotein E knockout background inhibits the progression of atherosclerosis, whereas re-expression of Cav-1 in the endothelium promotes lesion expansion. Although Cav-1-null mice are useful to delineate the importance of caveolae in atherosclerosis, there are additional problems that are difficult to dissect because loss of Cav-1 abolishes both the caveolae organelle as well as the Cav-1-mediated signaling pathways. To study how Cav-1 influences the progression of atherosclerosis in mice with caveolae, we generated a transgenic mouse that overexpresses Cav-1 in the endothelial cells in an apolipoprotein E-deficient background. We found that endothelial-specific overexpression of Cav-1 enhanced the progression of atherosclerosis in mice. Mechanistically, overexpression of Cav-1 reduced endothelial cell proliferation, migration, and nitric oxide production in vitro and increased expression of vascular cell adhesion molecule-1 in vivo. PMID:20581061

  7. Dietary Fats and Platelet Functions in Relation to Atherosclerosis and Coronary Heart Disease

    Microsoft Academic Search

    S. Renaud; R. Morazain; L. McGregor; F. Baudier

    1979-01-01

    Results in animals and in man indicate that in many circumstances, lipemia is not closely related to the severity of atherosclerosis nor to the incidence of coronary heart disease (CHD) or the intake of saturated fats as observed in paired studies between farmers from Moselle and Var in France and from West and East Scotland. In rabbits, an increased response

  8. The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models

    Microsoft Academic Search

    Alma Zernecke; Peter Libby; Christian Weber

    2008-01-01

    Chronic inflammation drives the development of atherosclerosis, and details regarding the involvement of different leukocyte subpopulations in the pathology of this disease have recently emerged. This Review highlights the surprising contribution of granulocyte subsets and mast cells to early atherogenesis and subsequent plaque instability, and describes the complex, double-edged role of monocyte, macrophage and dendritic-cell subsets through crosstalk with T

  9. Vascular repair by circulating endothelial progenitor cells: the missing link in atherosclerosis?

    Microsoft Academic Search

    Stefanie Dimmeler; Andreas M. Zeiher

    2004-01-01

    The integrity and functional activity of the endothelial monolayer play a crucial role in the prevention of atherosclerosis. Increasing evidence suggests that risk factors for coronary artery disease increase endothelial cell apoptosis and lead to a disturbance in the endothelial monolayer. Recent insights suggest that the injured endothelial monolayer is regenerated by circulating bone marrow derived endothelial progenitor cells, which

  10. Simulation of a pulsatile non-Newtonian flow past a stenosed 2D artery with atherosclerosis

    E-print Network

    Luo, Haoxiang

    shear stress Wall normal stress Atherosclerosis Navier­Stokes equations Computational fluid dynamics of China, 96 Jinzhai Road, Hefei, Anhui 230026, PR China a r t i c l e i n f o Article history: Received 9 February 2013 Accepted 29 May 2013 Keywords: Blood flow Pulsatile flow Non-Newtionian fluid Stenosis Wall

  11. Ultrasound carotid artery intima-media thickness assessment for progression of atherosclerosis in lipid intervention studies.

    PubMed

    Naqvi, Tasneem Z

    2008-03-01

    Atherosclerotic cardiovascular disease is the number one cause of death in Western countries and is a rapidly growing problem worldwide. The majority of patients who present with acute coronary syndrome often have a low cardiovascular risk score, which is insufficient to warrant treatment prior to an acute coronary event. Alternatively, some high risk individuals never develop cardiovascular events. Identification of individuals who are truly at risk before an acute coronary event is critical. The long subclinical incubation period of atherosclerosis and the early involvement of the vessel wall in the disease provides an opportunity to evaluate the presence of atherosclerosis by imaging the arterial wall and to initiate treatment measures prior to an acute coronary event. The assessment of the thickness of the intima-media layer of the vessel wall, as well as detection of early plaques by ultrasound, is non-invasive and is the most sensitive, reliable, and safe method to detect those at risk. It is also the most validated method to detect progression of atherosclerosis. Evaluation of atherosclerosis progression by this technique has been used in large clinical trial settings, however, improvement in imaging and measurement technology may make this suitable for use in individual patients for therapeutic validity both in primary and secondary care settings. PMID:18311661

  12. 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.

  13. Enhanced LDL oxidation in uremic patients: An additional mechanism for accelerated atherosclerosis?

    Microsoft Academic Search

    Elena Maggi; Roberto Bellazzi; Francesco Falaschi; Arturo Frattoni; Guido Perani; Giorgio Finardi; Antonietta Gazo; Maurizio Nai; Dino Romanini; Giorgio Bellomo

    1994-01-01

    Enhanced LDL oxidation in uremic patients: An additional mechanism for accelerated atherosclerosis? Since oxidized low-density lipoprotein (LDL) is more atherogenic than native LDL, LDL oxidation was investigated in uremic patients who often develop accelerated atherogenesis. Three groups of uremic patients were studied (10 on predialysis conservative therapy, 11 on repetitive hemodialysis, 13 on peritoneal dialysis) and compared with seventy matched

  14. Coronary atherosclerosis is already ongoing in pre-diabetic status: Insight from intravascular imaging modalities.

    PubMed

    Kurihara, Osamu; Takano, Masamichi; Seino, Yoshihiko; Shimizu, Wataru; Mizuno, Kyoichi

    2015-02-15

    Diabetes mellitus is a powerful risk factor of coronary artery disease (CAD), leading to death and disability. In recent years, given the accumulating evidence that prediabetes is also related to increasing risk of CAD including cardiovascular events, a new guideline has been proposed for the treatment of blood cholesterol for primary prevention of cardiovascular events. This guideline recommends aggressive lipid-lowering statin therapy for primary prevention in diabetes and other patients. The ultimate goal of patient management is to inhibit progression of systemic atherosclerosis and prevent fatal cardiovascular events such as acute coronary syndrome (ACS). Because disruption of atherosclerotic coronary plaques is a trigger of ACS, the high-risk atheroma is called a vulnerable plaque. Several types of novel diagnostic imaging technologies have been developed for identifying the characteristics of coronary atherosclerosis before the onset of ACS, especially vulnerable plaques. According to coronary angioscopic evaluation, atherosclerosis severity and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable to that in diabetic patients. In addition, pharmacological intervention by statin therapy changed plaque color and complexity, and the dynamic changes in plaque features are considered plaque stabilization. In this article, we review the findings of atherosclerosis in prediabetes, detected by intravascular imaging modalities, and the therapeutic implications. PMID:25685289

  15. Effect of Oral Postmenopausal Hormone Replacement on Progression of Atherosclerosis A Randomized, Controlled Trial

    Microsoft Academic Search

    Peter Angerer; Stefan Störk; Wolfgang Kothny; Philip Schmitt; Clemens von Schacky

    2010-01-01

    Postmenopausal hormone replacement therapy (HRT) is associated with low cardiovascular morbidity and mortality in epidemiological studies. Yet, no randomized trial has examined whether HRT is effective for prevention of coronary heart disease (CHD) in women with increased risk. The objective of this study was to determine whether HRT can slow progression of atherosclerosis, measured as intima-media thickness (IMT) in carotid

  16. Red wine, dealcoholized red wine, and especially grape juice, inhibit atherosclerosis in a hamster model

    Microsoft Academic Search

    Joe A. Vinson; Karolyn Teufel; Nancy Wu

    2001-01-01

    The French have low coronary heart disease mortality with high fat consumption; this epidemiological anomaly is known as the ‘French Paradox’ and is commonly attributed to the consumption of red wine. However, epidemiology studies have not convincingly shown a superiority of red wine vs. alcohol or other alcoholic beverages. We have used the hamster model of atherosclerosis to determine the

  17. Measuring progression and regression of coronary atherosclerosis in clinical trials: problems and progress

    Microsoft Academic Search

    Jacques Lespérance; David Waters

    1992-01-01

    Interventions that may influence the evolution of coronary atherosclerosis can be evaluated more rapidly and efficiently in clinical trials with angiographic endpoints as opposed to using coronary events as endpoints. Quantitative coronary arteriography provides precise and reproducible measurements of coronary artery dimensions for this purpose. The variability of 2 quantitative systems was assessed in 54 lesions under 4 different conditions:-same

  18. Increased heterogeneity of coronary perfusion in patients with early coronary atherosclerosis

    Microsoft Academic Search

    Heinrich Wieneke; Axel Schmermund; Junbo Ge; Christoph Altmann; Michael Haude; Clemens von Birgelen; Dietrich Baumgart; Olaf Dirsch; Raimund Erbel

    2001-01-01

    Background In patients with typical angina but angiographically normal coronary arteries, abnormal vasomotor function is assumed to be a major underlying cause. However, data on this issue are conflicting, and recent studies suggest that fluid dynamic abnormalities exist in these patients. The aim of the study was to evaluate whether early stages of atherosclerosis are characterized by alterations of baseline

  19. 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

  20. Citrullus lanatus `Sentinel' (Watermelon) Extract Reduces Atherosclerosis in LDL Receptor Deficient Mice

    PubMed Central

    Poduri, Aruna; Rateri, Debra L.; Saha, Shubin K.; Saha, Sibu; Daugherty, Alan

    2012-01-01

    Watermelon (Citrullus lanatus or C. lanatus) has many potentially bioactive compounds including citrulline, which may influence atherosclerosis. In this study, we determined the effects of C. lanatus, provided as an extract of the cultivar `sentinel', on hypercholesterolemia-induced atherosclerosis in mice. Male LDL receptor deficient mice at 8 weeks old were given either C. lanatus `sentinel' extract (2% vol/vol; n=10) or a mixture of matching carbohydrates (2% vol/vol; n=8) as the control in drinking water, while fed a saturated fat-enriched diet for 12 weeks ad libitum. Mice consuming C. lanatus `sentinel' extract had significantly increased plasma citrulline concentrations. Systolic blood pressure was comparable between the two groups. Consumption of C. lanatus `sentinel' extract led to lower body weight and fat mass without influencing lean mass. There were no differences in food and water intake, and urine output between the two groups. C. lanatus `sentinel' extract administration decreased plasma cholesterol concentrations that were attributed to reductions of intermediate/low density lipoprotein cholesterol. Plasma concentrations of MCP-1 and IFN-? were decreased and IL-10 increased in mice consuming C. lanatus `sentinel' extract. Intake of C. lanatus `sentinel' extract resulted in reductions of atherosclerosis in both aortic arch and thoracic regions. In conclusion, consumption of C. lanatus `sentinel' extract led to reduced body weight gain, decreased plasma cholesterol concentrations, improved homeostasis of pro- and anti-inflammatory cytokines, and attenuated development of atherosclerosis without affecting systolic blood pressure in hypercholesterolemic mice. PMID:22902326

  1. Peptidylarginine Deiminase Inhibition Reduces Vascular Damage and Modulates Innate Immune Responses in Murine Models of Atherosclerosis

    PubMed Central

    Knight, Jason S.; Luo, Wei; O’Dell, Alexander A.; Yalavarthi, Srilakshmi; Zhao, Wenpu; Subramanian, Venkataraman; Guo, Chiao; Grenn, Robert C.; Thompson, Paul R.; Eitzman, Daniel T.; Kaplan, Mariana J.

    2014-01-01

    Rationale Neutrophil extracellular trap (NET) formation promotes vascular damage, thrombosis, and activation of interferon-?-producing plasmacytoid dendritic cells in diseased arteries. Peptidylarginine deiminase inhibition is a strategy that can decrease in vivo NET formation. Objective To test whether peptidylarginine deiminase inhibition, a novel approach to targeting arterial disease, can reduce vascular damage and inhibit innate immune responses in murine models of atherosclerosis. Methods and Results Apolipoprotein-E (Apoe)?/? mice demonstrated enhanced NET formation, developed autoantibodies to NETs, and expressed high levels of interferon-? in diseased arteries. Apoe?/? mice were treated for 11 weeks with daily injections of Cl-amidine, a peptidylarginine deiminase inhibitor. Peptidylarginine deiminase inhibition blocked NET formation, reduced atherosclerotic lesion area, and delayed time to carotid artery thrombosis in a photochemical injury model. Decreases in atherosclerosis burden were accompanied by reduced recruitment of netting neutrophils and macrophages to arteries, as well as by reduced arterial interferon-? expression. Conclusions Pharmacological interventions that block NET formation can reduce atherosclerosis burden and arterial thrombosis in murine systems. These results support a role for aberrant NET formation in the pathogenesis of atherosclerosis through modulation of innate immune responses. PMID:24425713

  2. Body Fat Distribution as a Risk Factor for Coronary Artery Atherosclerosis in Female Cynomolgus Monkeys

    Microsoft Academic Search

    Carol A. Shively; Thomas B. Clarkson; L Cheryl Miller; Kurt W. Weingand

    Central fat deposition Is associated with Increased risk of coronary heart disease morbidity and mortality In women. Subcutaneous fat distribution was Investigated as a potential factor that might exacerbate diet-Induced coronary artery atherosclerosis (CAA) in female cynomolgus monkeys (Macaca fasclcularls) which share with North American Caucasian women a gender-related protection against CAA. In a retrospec- tive necropsy study (n =

  3. 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.

  4. Effect of dietary fats on blood cholesterol and lipid and the development of atherosclerosis in rabbits

    Microsoft Academic Search

    Sun Jin Hur; Min Du; Kichang Nam; Mark Williamson; Dong Uk Ahn

    2005-01-01

    The objective of this study was to determine the effects of dietary fat on the development of atherosclerosis and changes in blood lipids in rabbits. Forty New Zealand White rabbits were divided into 5 groups and fed commercial rabbit chow with 0% oil (control), 2% corn oil, 2% fish oil, 2% oxidized oil, or 2% heated corn oil. Cholesterol (CHO,

  5. Wall Shear Stress and Atherosclerosis: Numerical Blood Flow Simulations in the Mouse Aortic Arch

    Microsoft Academic Search

    P. RUENGSAKULRACH; A. K. JOSHIb; S. FREMESc; A. K. Joshi; S. Fremes; S. Foster

    2008-01-01

    The aims of this study were (1) to demonstrate the feasibility of computational fluid dynamic (CFD) modelling of realistic blood flow in the mouse aortic arch, and (2) to determine the relation of wall shear stress and atherosclerosis in the mouse aortic arch. ApoE knockout mice were chosen for this study. The blood flow fraction in the major branches of

  6. Wall Shear Stress and Atherosclerosis: Numerical Blood Flow Simulations in the Mouse Aortic Arch

    Microsoft Academic Search

    P. RUENGSAKULRACH; A. K. JOSHI; S. FREMES; J. BUTANY; Y. LENBURY

    The aims of this study were (1) to demonstrate the feasibility of computational fluid dynamic (CFD) modelling of realistic blood flow in the mouse aortic arch, and (2) to determine the relation of wall shear stress and atherosclerosis in the mouse aortic arch. ApoE knockout mice were chosen for this study. The blood flow fraction in the major branches of

  7. Anti-Inflammatory and Immunomodulatory Mechanism of Tanshinone IIA for Atherosclerosis

    PubMed Central

    Chen, Zhuo

    2014-01-01

    Tanshinone IIA (Tan II A) is widely used in the treatment of cardiovascular diseases as an active component of Salvia miltiorrhiza Bunge. It has been demonstrated to have pleiotropic effects for atherosclerosis. From the anti-inflammatory and immunomodulatory mechanism perspective, this paper reviewed major progresses of Tan IIA in antiatherosclerosis research, including immune cells, antigens, cytokines, and cell signaling pathways. PMID:25525444

  8. Evidence for Association Between Polycystic Ovary Syndrome and Premature Carotid Atherosclerosis in Middle-Aged Women

    Microsoft Academic Search

    Evelyn O. Talbott; David S. Guzick; Kim Sutton-Tyrrell; Kathleen P. McHugh-Pemu; Jeanne V. Zborowski; Karen E. Remsberg; Lewis H. Kuller

    2010-01-01

    Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance. An adverse lipid profile has also been observed in PCOS-affected women, suggesting that these individuals may be at increased risk for coronary heart disease at a young age. The objective of the present study was to evaluate subclinical atherosclerosis among women with PCOS

  9. Genetic evidence supporting a critical role of endothelial caveolin-1 during the progression of atherosclerosis.

    PubMed

    Fernández-Hernando, Carlos; Yu, Jun; Suárez, Yajaira; Rahner, Christoph; Dávalos, Alberto; Lasunción, Miguel A; Sessa, William C

    2009-07-01

    The accumulation of LDL-derived cholesterol in the artery wall is the initiating event that causes atherosclerosis. However, the mechanisms that lead to the initiation of atherosclerosis are still poorly understood. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in promoting atherogenesis. Mice were generated lacking Cav-1 and apoE but expressing endothelial-specific Cav-1 in the double knockout background. Genetic ablation of Cav-1 on an apoE knockout background inhibits the progression of atherosclerosis, while re-expression of Cav-1 in the endothelium promotes lesion expansion. Mechanistically, the loss of Cav-1 reduces LDL infiltration into the artery wall, promotes nitric oxide production, and reduces the expression of leukocyte adhesion molecules, effects completely reversed in transgenic mice. In summary, this unique model provides physiological evidence supporting the important role of endothelial Cav-1 expression in regulating the entry of LDL into the vessel wall and the initiation of atherosclerosis. PMID:19583953

  10. Genetic evidence supporting a critical role of endothelial caveolin-1 during the progression of atherosclerosis

    PubMed Central

    Fernández-Hernando, Carlos; Yu, Jun; Suárez, Yajaira; Rahner, Christoph; Dávalos, Alberto; Lasunción, Miguel A.; Sessa, William C.

    2009-01-01

    SUMMARY The accumulation of LDL-derived cholesterol in the artery wall is the initiating event that causes atherosclerosis. However, the mechanisms that lead to the initiation of atherosclerosis are still poorly understood. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in promoting atherogenesis. Mice were generated lacking Cav-1 and apoE but expressing endothelial-specific Cav-1 in the double knockout background. Genetic ablation of Cav-1 on an apoE knockout background inhibits the progression of atherosclerosis while re-expression of Cav-1 in the endothelium promotes lesion expansion. Mechanistically, the loss of Cav-1 reduces LDL infiltration into the artery wall, promotes nitric oxide production and reduces the expression of leukocyte adhesion molecules, effects completely reversed in transgenic mice. In summary, this unique model provides physiological evidence supporting the important role of endothelial Cav-1 expression in regulating the entry of LDL into the vessel wall and the initiation of atherosclerosis. PMID:19583953

  11. 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...

  12. 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...

  13. Reporting standards for angioplasty and stent-assisted angioplasty for intracranial atherosclerosis

    Microsoft Academic Search

    H Christian Schumacher; Philip M Meyers; Randall T Higashida; Colin P Derdeyn; Sean D Lavine; Gary M Nesbit; David Sacks; Peter Rasmussen; Lawrence R Wechsler

    2010-01-01

    Background and purposeIntracranial cerebral atherosclerosis causes ischemic stroke in a significant number of patients. Technological advances over the past 10 years have enabled endovascular treatment of intracranial atherosclerotic stenosis. The number of patients treated with angioplasty or stent-assisted angioplasty for this condition is increasing. Given the lack of universally accepted definitions, the goal of this document is to provide consensus

  14. Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPAR?, ?/?, and ?

    PubMed Central

    Li, Andrew C.; Binder, Christoph J.; Gutierrez, Alejandra; Brown, Kathleen K.; Plotkin, Christine R.; Pattison, Jennifer W.; Valledor, Annabel F.; Davis, Roger A.; Willson, Timothy M.; Witztum, Joseph L.; Palinski, Wulf; Glass, Christopher K.

    2004-01-01

    PPAR?, ?/?, and ? regulate genes involved in the control of lipid metabolism and inflammation and are expressed in all major cell types of atherosclerotic lesions. In vitro studies have suggested that PPARs exert antiatherogenic effects by inhibiting the expression of proinflammatory genes and enhancing cholesterol efflux via activation of the liver X receptor–ABCA1 (LXR-ABCA1) pathway. To investigate the potential importance of these activities in vivo, we performed a systematic analysis of the effects of PPAR?, ?, and ? agonists on foam-cell formation and atherosclerosis in male LDL receptor–deficient (LDLR–/–) mice. Like the PPAR? agonist, a PPAR?-specific agonist strongly inhibited atherosclerosis, whereas a PPAR?-specific agonist failed to inhibit lesion formation. In concert with their effects on atherosclerosis, PPAR? and PPAR? agonists, but not the PPAR? agonist, inhibited the formation of macrophage foam cells in the peritoneal cavity. Unexpectedly, PPAR? and PPAR? agonists inhibited foam-cell formation in vivo through distinct ABCA1-independent pathways. While inhibition of foam-cell formation by PPAR? required LXRs, activation of PPAR? reduced cholesterol esterification, induced expression of ABCG1, and stimulated HDL-dependent cholesterol efflux in an LXR-independent manner. In concert, these findings reveal receptor-specific mechanisms by which PPARs influence macrophage cholesterol homeostasis. In the future, these mechanisms may be exploited pharmacologically to inhibit the development of atherosclerosis. PMID:15578089

  15. 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...

  16. 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...

  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. Cholesteryl ester transfer protein and atherosclerosis in Japanese subjects: a study based on coronary angiography

    Microsoft Academic Search

    Akitomo Goto; Kanna Sasai; Shogo Suzuki; Tatsuya Fukutomi; Shigenori Ito; Toyoaki Matsushita; Mitsuhiro Okamoto; Takahiko Suzuki; Makoto Itoh; Kuniko Okumura-Noji; Shinji Yokoyama

    2001-01-01

    We undertook a cross-sectional analysis on CETP and atherosclerosis among Japanese subjects, by means of CETP mass assay, its gene polymorphism and coronary angiogram. The 110 consecutive patients who underwent coronary angiography were enrolled into the study except for those over 70 years and taking lipid-lowering drugs. Association was analyzed among plasma lipid and lipoproteins, CETP mass, its gene polymorphisms

  19. 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

    ...accuracy of the agency's estimate of the burden...Atherosclerosis Risk in Communities Study (ARIC),--Revised...cardiovascular diseases among men, women, African Americans and white persons in four U.S. communities: Forsyth...primary objectives of the study are to: (1)...

  20. Myeloperoxidase genetic polymorphisms modulate human neutrophil enzyme activity: Genetic determinants for atherosclerosis?

    Microsoft Academic Search

    Isabelle Chevrier; David-Alexandre Tregouet; Simone Massonnet-Castel; Philippe Beaune; Marie-Anne Loriot

    2006-01-01

    ObjectiveMyeloperoxidase (MPO), an abundant leukocyte hemoprotein has been linked to atherosclerosis and cardiovascular disease. We previously found new genetic polymorphisms in MPO gene. The purpose of this study was to evaluate the influences of these polymorphisms on human neutrophil MPO activity by means of haplotype analysis.

  1. Direct viewing of atherosclerosis in vivo: plaque invasion by leukocytes is initiated by the endothelial selectins

    Microsoft Academic Search

    EINAR E. ERIKSSON; XUN XIE; JOACHIM WERR; PETER THOREN; LENNART LINDBOM

    2001-01-01

    Leukocyte infiltration in atherosclerosis has been extensively investigated by using histological techniques on fixed tissues. In this study, intravital microscopic observations of leukocyte recruitment in the aorta of atherosclerotic mice were performed. Interactions between leukocytes and atherosclerotic endothelium were highly transient, thereby limiting the ability for rolling leukocytes to firmly adhere. Leuko- cyte rolling was abolished by function inhibition of

  2. Band neutrophil count and the presence and severity of coronary atherosclerosis

    Microsoft Academic Search

    Hiroshi Kawaguchi; Tsukasa Mori; Tomoki Kawano; Suminori Kono; Jun Sasaki; Kikuo Arakawa

    1996-01-01

    It has been consistently shown that the total blood leukocyte count is an independent risk factor for coronary artery disease. Few studies, however, have addressed the relation between differential leukocyte counts and coronary artery disease. We investigated the relation of total and differential leukocyte counts to angiographically determined coronary atherosclerosis. The study included 486 subjects (335 men, 151 women) who

  3. Monocyte-Targeting Supramolecular Micellar Assemblies: A Molecular Diagnostic Tool for Atherosclerosis

    PubMed Central

    Chung, E. J.; Nord, K.; Sugimoto, M. J.; Wonder, E.; Tirrell, M.; Mlinar, L. B.; Alenghat, F. J.; Fang, Y.

    2014-01-01

    Atherosclerosis is a multifactorial inflammatory disease that can progress silently for decades and result in myocardial infarction, stroke, and death. Diagnostic imaging technologies have made great strides to define the degree of atherosclerotic plaque burden through the severity of arterial stenosis. However, current technologies cannot differentiate more lethal “vulnerable plaques,” and are not sensitive enough for preventive medicine. Imaging early molecular markers and quantifying the extent of disease progression continues to be a major challenge in the field. To this end, monocyte-targeting, peptide amphiphile micelles (PAMs) are engineered through the incorporation of the chemokine receptor CCR2-binding motif of monocyte chemoattractant protein-1 (MCP-1) and MCP-1 PAMs are evaluated preclinically as diagnostic tools for atherosclerosis. Monocyte-targeting is desirable as the influx of monocytes is a marker of early lesions, accumulation of monocytes is linked to atherosclerosis progression, and rupture-prone plaques have higher numbers of monocytes. MCP-1 PAMs bind to monocytes in vitro, and MCP-1 PAMs detect and discriminate between early- and late-stage atherosclerotic aortas. Moreover, MCP-1 PAMs are found to be eliminated via renal clearance and the mononuclear phagocyte system (MPS) without adverse side effects. Thus, MCP-1 PAMs are a promising new class of diagnostic agents capable of monitoring the progression of atherosclerosis. PMID:25156590

  4. Monocyte-targeting supramolecular micellar assemblies: a molecular diagnostic tool for atherosclerosis.

    PubMed

    Chung, Eun Ji; Mlinar, Laurie B; Nord, Kathryn; Sugimoto, Matthew J; Wonder, Emily; Alenghat, Francis J; Fang, Yun; Tirrell, Matthew

    2015-02-18

    Atherosclerosis is a multifactorial inflammatory disease that can progress silently for decades and result in myocardial infarction, stroke, and death. Diagnostic imaging technologies have made great strides to define the degree of atherosclerotic plaque burden through the severity of arterial stenosis. However, current technologies cannot differentiate more lethal "vulnerable plaques," and are not sensitive enough for preventive medicine. Imaging early molecular markers and quantifying the extent of disease progression continues to be a major challenge in the field. To this end, monocyte-targeting, peptide amphiphile micelles (PAMs) are engineered through the incorporation of the chemokine receptor CCR2-binding motif of monocyte chemoattractant protein-1 (MCP-1) and MCP-1 PAMs are evaluated preclinically as diagnostic tools for atherosclerosis. Monocyte-targeting is desirable as the influx of monocytes is a marker of early lesions, accumulation of monocytes is linked to atherosclerosis progression, and rupture-prone plaques have higher numbers of monocytes. MCP-1 PAMs bind to monocytes in vitro, and MCP-1 PAMs detect and discriminate between early- and late-stage atherosclerotic aortas. Moreover, MCP-1 PAMs are found to be eliminated via renal clearance and the mononuclear phagocyte system (MPS) without adverse side effects. Thus, MCP-1 PAMs are a promising new class of diagnostic agents capable of monitoring the progression of atherosclerosis. PMID:25156590

  5. IRON AND ATHEROSCLEROSIS: IRON CHELATORS DECREASE ADHESION OF MONOCYTES TO VASCULAR ENDOTHELIUM

    Microsoft Academic Search

    R. Kartikasari; N. A. Georgiou; B. Sweder van Asbeck; I. J. M. Marx

    2003-01-01

    Besides the fact that it is a vital element in life, iron may also participate in diverse pathological processes. It has been hypothesised that iron is involved in the development of atherosclerosis and related cardiovascular diseases. Several epidemiological studies as well as in vivo and in vitro experiments are in favour for this iron hypothesis, although some studies have yielded

  6. 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

  7. Animal, In Vitro, and Ex Vivo Models of Flow-Dependent Atherosclerosis: Role of Oxidative Stress

    PubMed Central

    Rezvan, Amir; Ni, Chih-Wen; Alberts-Grill, Noah

    2011-01-01

    Abstract Atherosclerosis is an inflammatory disease preferentially occurring in curved or branched arterial regions, whereas straight parts of the arteries are protected, suggesting a close relationship between flow and atherosclerosis. However, evidence directly linking disturbed flow to atherogenesis is just emerging, thanks to the recent development of suitable animal models. In this article, we review the status of various animal, in vitro, and ex vivo models that have been used to study flow-dependent vascular biology and atherosclerosis. For animal models, naturally flow-disturbed regions such as branched or curved arterial regions as well as surgically created models, including arterio-venous fistulas, vascular grafts, perivascular cuffs, and complete, incomplete, or partial ligation of arteries, are used. Although in vivo models provide the environment needed to mimic the complex pathophysiological processes, in vitro models provide simple conditions that allow the study of isolated factors. Typical in vitro models use cultured endothelial cells exposed to various flow conditions, using devices such as cone-and-plate and parallel-plate chambers. Ex vivo models using isolated vessels have been used to bridge the gap between complex in vivo models and simple in vitro systems. Here, we review these flow models in the context of the role of oxidative stress in flow-dependent inflammation, a critical proatherogenic step, and atherosclerosis. Antioxid. Redox Signal. 15, 1433–1448. PMID:20712399

  8. Inflammation Is a Crucial Feature of Atherosclerosis and a Potential Target to Reduce Cardiovascular Events

    Microsoft Academic Search

    François Mach

    Contrary to popular opinion, atherosclerosis is not a disease unique to modern civilization. In fact, atherosclerotic lesions have been found in the arteries of mummies dating back to 1,500 b.c., and yet our understanding of this complex process is still evolving. A fusion of basic science advances and clinical research findings has radically altered our traditional concepts about the pathogenesis

  9. Therapeutic potential of vitamin E in the pathogenesis of spontaneous atherosclerosis.

    PubMed

    Janero, D R

    1991-01-01

    Spontaneous atherosclerosis is largely an occlusive disease of medium-size arteries whose progression in a hyperlipidemic environment reflects chronic interactions among injury stimuli to the vessel wall and "responses to injury" by vascular tissue and certain blood components. Development of vessel lesions in animal models of spontaneous atherosclerosis and (at least in principle) in man largely reflects responses of three major cell types (vascular endothelial cells, vascular smooth muscle cells, monocytes-macrophages) as well as the content and distribution of lipids among various lipoprotein subclasses and the increased atherogenicity of modified (e.g., oxidized) lipoproteins. The severe clinical complications associated with spontaneous atherosclerosis, along with its rather common incidence in man, have focused attention on the prevention and therapy of this vascular disease state. Some pharmacological studies in animal models of spontaneous atherosclerosis and some retrospective epidemiological studies in man suggest that vitamin E, the principal (if not sole) lipid-soluble chain-breaking tissue antioxidant, might have therapeutic benefit as an antiatherosclerotic agent. This suggestion gains support from a variety of compelling in vitro evidence demonstrating direct influences of vitamin E on cells and lipoproteins likely involved in the pathogenesis of spontaneous atherosclerosis. Biochemical and cellular data indicate that the potential antiatherogenic activity of vitamin E could reflect its activities as a regulator of endothelial, smooth muscle, or monocyte-macrophage function, an inhibitor of endothelial membrane lipid peroxidation, a modulator of plasma lipid levels and lipid distribution among circulating lipoproteins, and a preventor of lipoprotein oxidative modification. On the other hand, there is a comparative lack of conclusive evidence from animal models regarding: (a) the importance to atherogenesis of vascular and cellular processes modulated by vitamin E; (b) the influence of vitamin E on these processes in vivo and, consequently, on the initiation/progression of spontaneous atherosclerosis. Therefore, pharmacologic investigation of vitamin E (and synthetic, vitamin E-like antioxidants) in nutritional and hyperlipidemic animal models of spontaneous atherosclerosis is required to establish whether any atherosclerotic impact is associated with vitamin E and, if so, what the mechanistic basis of the therapeutic benefit is. Such a line of experimental inquiry should also increase our understanding of the pathogenesis of atherosclerotic vessel disease per se. PMID:1937126

  10. 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.

  11. -uncertainty Anonymization by Partial Suppression

    E-print Network

    Zhu, Kenny Q.

    -uncertainty Anonymization by Partial Suppression Xiao Jia1 , Chao Pan1 , Xinhui Xu1 , Kenny Q. Zhu 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

  12. Local factors modify the dose dependence of 56Fe-induced atherosclerosis.

    NASA Astrophysics Data System (ADS)

    Kucik, Dennis; Gupta, Kiran; Wu, Xing; Yu, Tao; Chang, Polly; Kabarowski, Janusz; Yu, Shaohua

    2012-07-01

    Radiation exposure from a number of terrestrial sources is associated with an increased risk of cardiovascular disease, but evidence establishing whether high-LET radiation has similar effects has been lacking. We recently demonstrated that 600 MeV/n 56Fe induces atherosclerosis as well. Ten-week old male apolipoprotein-E deficient mice, a well-characterized atherosclerosis animal model, were exposed to 0 (control) 2, or 5Gy 56Fe targeted to the chest and neck. In these mice, 56Fe-induced atherosclerosis was similar in character to that induced by X-rays in the same mouse model and to that resulting from therapeutic radiation in cancer patients. Atherosclerosis was exacerbated by 56Fe only in targeted areas, however, suggesting a direct effect of the radiation on the arteries themselves. This is in contrast to some other risk factors, such as high cholesterol or tobacco use, which have systemic effects. The radiation dose required to accelerate development of atherosclerotic plaques, however, differed depending on the vessel that was irradiated and even the location within the vessel. For example, atherosclerosis in the aortic arch was accelerated only by the highest dose (5 Gy), while the carotid arteries and the aortic root showed effects at 2 Gy (a dose four- to eight-fold lower than the dose of X-rays that produces similar effects in this model). Since shear stress is disrupted in the area of the aortic root, it is likely that at least part of the site-specificity is due to additive or synergistic effects of radiation and local hydrodynamics. Other factors, such as local oxidative stress or gene expression may also have been involved. Since the pro-atherogenic effects of 56Fe depend on additional local factors, this suggests that radiation exposure, when unavoidable, might be mitigated by modification of factors unrelated to the radiation itself.

  13. 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

  14. Correlation study on adiponectin gene SNP45 and long-term oxidative stress in patients with diabetes and carotid atherosclerosis.

    PubMed

    Piao, Lianshan; Han, Yanhua; Li, Dan

    2014-09-01

    The aim of the present study was to investigate the correlation between the adiponectin gene single nucleotide polymorphism (SNP)45 T/G and long-term oxidative stress in type II diabetes mellitus (T2DM) patients with carotid atherosclerosis. Patients with T2DM were divided into non-carotid atherosclerosis and carotid atherosclerosis groups, which were then subsequently divided into TT and TG + GG groups according to the adiponectin SNP45 T/G genotypes. Enzyme-linked immunosorbent assay, TaqMan probe quantitative polymerase chain reaction (PCR), PCR-TaqMan, color Doppler and other methods were used to determine the adiponectin levels, gene polymorphisms, acquired mitochondrial DNA (mtDNA) A3243G somatic cell mutation rates and the carotid intima-media thickness. The somatic cell mutation rate of acquired mtDNA A3243A/G in the T2DM carotid atherosclerosis group was significantly higher compared with the group without carotid atherosclerosis. In addition, the acquired mtDNA A3243A/G somatic cell mutation rate in the T2DM carotid atherosclerosis group with the adiponectin gene SNP45 TT genotype was significantly lower compared with the SNP45 TG/GG genotype group. T2DM combined with carotid atherosclerosis was associated with long-term oxidative stress. In addition, adiponectin gene SNP45 T/G was associated with increased mtDNA A3243A/G somatic mutation rates in T2DM patients with carotid atherosclerosis. Therefore, adiponectin gene polymorphisms may lead to diabetes atherosclerosis through oxidative stress. PMID:25120586

  15. Sound can suppress visual perception.

    PubMed

    Hidaka, Souta; Ide, Masakazu

    2015-01-01

    In a single modality, the percept of an input (e.g., voices of neighbors) is often suppressed by another (e.g., the sound of a car horn nearby) due to close interactions of neural responses to these inputs. Recent studies have also suggested that close interactions of neural responses could occur even across sensory modalities, especially for audio-visual interactions. However, direct behavioral evidence regarding the audio-visual perceptual suppression effect has not been reported in a study with humans. Here, we investigated whether sound could have a suppressive effect on visual perception. We found that white noise bursts presented through headphones degraded visual orientation discrimination performance. This auditory suppression effect on visual perception frequently occurred when these inputs were presented in a spatially and temporally consistent manner. These results indicate that the perceptual suppression effect could occur across auditory and visual modalities based on close and direct neural interactions among those sensory inputs. PMID:26023877

  16. Sound can suppress visual perception

    PubMed Central

    Hidaka, Souta; Ide, Masakazu

    2015-01-01

    In a single modality, the percept of an input (e.g., voices of neighbors) is often suppressed by another (e.g., the sound of a car horn nearby) due to close interactions of neural responses to these inputs. Recent studies have also suggested that close interactions of neural responses could occur even across sensory modalities, especially for audio-visual interactions. However, direct behavioral evidence regarding the audio-visual perceptual suppression effect has not been reported in a study with humans. Here, we investigated whether sound could have a suppressive effect on visual perception. We found that white noise bursts presented through headphones degraded visual orientation discrimination performance. This auditory suppression effect on visual perception frequently occurred when these inputs were presented in a spatially and temporally consistent manner. These results indicate that the perceptual suppression effect could occur across auditory and visual modalities based on close and direct neural interactions among those sensory inputs. PMID:26023877

  17. The role of infection in atherosclerosis and coronary artery disease: a new therapeutic target.

    PubMed

    Ismail, A; Khosravi, H; Olson, H

    1999-01-01

    There is growing evidence that inflammatory processes may be involved in the development of atherosclerosis and its complications. Viral and bacterial pathogens have been implicated as possible causative factors in the pathogenesis of coronary artery disease (CAD) and restenosis after angioplasty. Antibiotic trials are now in progress to examine whether treatment of infection can prevent the complications of CAD. Atherosclerosis, the primary pathologic process in coronary artery disease (CAD), carotid artery disease, abdominal aortic aneurysm, and peripheral vascular disease, is no longer considered to be an obscure, slowly progressive, degenerative disease. Indeed, recent molecular studies on the atherosclerotic plaque have shown that the initiation, progression, and acute sequelae of atherosclerosis can be explained in part by a low-grade inflammatory process. Studies show that mediators of inflammation can be found at all stages of the life cycle of the atherosclerotic plaque. These include activated macrophages and lymphocytes, cytokines, growth factors, matrix degenerating proteinases, and tissue factor. It is hypothesized that risk factors such as hypertension, smoking, or elevated levels of low-density lipoprotein (LDL) cholesterol result in injury to the endothelial cell of the artery, and this injury initiates the inflammatory process. However, many patients with vascular disease do not have these established risk factors, and this observation has galvanized efforts to find new risk factors. Because inflammation is now considered to be an operative paradigm for atherosclerosis, it is not a major leap to the hypothesis that infectious agents, such as viral or bacterial, may play a role. Certainly this is not a new concept, and with the recent discovery that peptic ulcer disease, heretofore considered a disease of excess acid and reduced mucosal resistance, is caused by the ubiquitous bacterium Helicobacter pylori, interest in finding an infectious etiology for atherosclerosis has increased. Accordingly, the purpose of this discussion is to review in a historical manner the evidence that infectious agents-including herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), Enterovirus (adenovirus, Coxsackie virus), Chlamydia pneumoniae, and H. pylori-may play a role in atherosclerosis and its manifestations, especially as they relate to CAD. PMID:11720630

  18. 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

  19. Overexpression of CCN3 Inhibits Inflammation and Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice

    PubMed Central

    Liu, Jun; Ren, Yingang; Kang, Li; Zhang, Lihua

    2014-01-01

    Background Cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed (CCN) 3 has been recently reported to play a role in regulating inflammation of vascular endothelial cells. However, the role of CCN3 in atherosclerosis, which is characterized by vascular inflammation, remains unclear. Hypothesis and Objectives Overexpression of CCN3 may relieve the inflammation response in and inhibit the progress of atherosclerosis. We aimed to explore the potential roles of CCN3 in inflammation in atherosclerosis. Strategy and Main Results In in vitro studies using cultured human aortic endothelial cells and human umbilical vein endothelial cells, CCN3 mRNA and protein expression significantly decreased in response to tumor necrosis factor-? and interleukin-1? treatments (p<0.05), when analyzed by quantitative real-time polymerase chain reaction and Western blot. Using a mouse model of atherosclerosis, the mRNA and protein levels of CCN3 decreased by 72.2% (p?=?0.041) and 86.4% (p?=?0.036), respectively, compared with levels in wild-type control mice, respectively. Overexpression of CCN3 by adenovirus-mediated gene overexpression decreased low-density lipoprotein cholesterol by 48.9% (p?=?0.017), total cholesterol by 58.9% (p?=?0.031), and triglycerides by 56.8% (p?=?0.022), and it increased high-density lipoprotein cholesterol level by 2.16-fold (p?=?0.039), compared with control groups. Additionally, a reduced plaque area and increased fibrous cap were observed (p<0.05). Furthermore, CCN3 overexpression decreased cell adhesion molecule-1 mRNA expression by 84.7% (p?=?0.007) and intercellular adhesion molecule-1 mRNA expression by 61.2% (p?=?0.044). Inflammatory factors, including matrix metalloproteinases, cyclooxygenase 2, and tissue factor also significantly (p<0.05) decreased with CCN3 overexpression in the atherosclerotic mouse model. Additionally, CCN1 and CCN2, which have been reported to be highly expressed in aortic atherosclerotic plaques, were significantly downregulated (p<0.05) by CCN3 overexpression. Conclusion CCN3 overexpression is associated with control of inflammatory processes and reversion of dyslipidemia in the process of atherosclerosis, which implies that CCN3 may be a promising target in the treatment of atherosclerosis. PMID:24722330

  20. 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...

  1. 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

    factors for atherosclerosis in avian species and learning ability, a series of studies were conducted in Monk parrots: 1) alterations comparing a high linoleic acid diet with -linolenic acid (ALA) diet on lipid metabolism, fatty acid conversions...

  2. Micronutrient intakes and their associations with markers of inflammation, subclinical atherosclerosis, cardiovascular disease, type II diabetes and metabolic syndrome

    Microsoft Academic Search

    Marcia C. C. de Oliveira

    2010-01-01

    We investigated cross-sectional associations between intakes of zinc, magnesium, heme- and non heme iron, beta-carotene, vitamin C and vitamin E and inflammation and subclinical atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). We also investigated prospective associations between those micronutrients and incident MetS, T2D and CVD. Participants between 45-84 years of age at baseline were followed between 2000 and 2007.

  3. Sustained suppression in congruency tasks.

    PubMed

    Notebaert, Wim; Soetens, Eric

    2006-01-01

    In a list version of the Stroop task, Thomas observed that Stroop interference was smaller when the irrelevant word was repeated through parts of the list. MacLeod formulated the sustained-suppression hypothesis for this effect. It is assumed that the automatic response activation on the basis of the irrelevant word is selectively suppressed. In this paper this hypothesis is further investigated. In a serial Stroop task with short response-stimulus interval (RSI) we demonstrate that the Stroop effect disappears when the irrelevant word is repeated, whereas the Stroop effect is evident when the word changes. With a long RSI, there is no influence of the sequence of the irrelevant word. The same pattern of results is observed in a flanker task. The results are discussed in terms of the activation-suppression model (Ridderinkhof) and the sustained-suppression hypothesis. PMID:16556566

  4. In Vivo Treg Suppression Assays

    PubMed Central

    Workman, Creg J.; Collison, Lauren W.; Bettini, Maria; Pillai, Meenu R.; Rehg, Jerold E.; Vignali, Dario A.A.

    2011-01-01

    To fully examine the functionality of a regulatory T cell (Treg) population, one needs to assess their ability to suppress in a variety of in vivo models. We describe five in vivo models that examine the suppressive capacity of Tregs upon different target cell types. The advantages and disadvantages of each model includ ing resources, time, and technical expertise required to execute each model are also described. PMID:21287333

  5. Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: Differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17?

    PubMed Central

    Ashlin, Tim G.; Kwan, Alvin P.L.; Ramji, Dipak P.

    2013-01-01

    Atherosclerosis is an inflammatory disease of the vasculature regulated by cytokines. Macrophages play a crucial role at all stages of this disease, including regulation of foam cell formation, the inflammatory response and stability of atherosclerotic plaques. For example, matrix metalloproteinases produced by macrophages play an important role in modulating plaque stability. More recently, the ADAMTS proteases, which are known to play a key role in the control of cartilage degradation during arthritis, have been found to be expressed in atherosclerotic lesions and suggested to have potentially important functions in the control of plaque stability. Unfortunately, the action of cytokines on the expression of ADAMTS family in macrophages is poorly understood. We have investigated the effect of classical cytokines (IFN-? and TGF-?) and those that have been recently identified (TL1A and IL-17) on the expression of ADAMTS-1, -4 and -5 in human macrophages. The expression of all three ADAMTS members was induced during differentiation of monocytes into macrophages. TGF-? had a differential action with induction of ADAMTS-1 and -5 expression and attenuation in the levels of ADAMTS-4. In contrast, IFN-? suppressed the expression of ADAMTS-1 without having an effect on ADAMTS-4 and -5. Although TL-1A or IL-17A alone had little effect on the expression of all the members, they induced their expression synergistically when present together. These studies provide new insight into the regulation of key ADAMTS family members in human macrophages by major cytokines in relation to atherosclerosis. PMID:23859810

  6. Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17.

    PubMed

    Ashlin, Tim G; Kwan, Alvin P L; Ramji, Dipak P

    2013-10-01

    Atherosclerosis is an inflammatory disease of the vasculature regulated by cytokines. Macrophages play a crucial role at all stages of this disease, including regulation of foam cell formation, the inflammatory response and stability of atherosclerotic plaques. For example, matrix metalloproteinases produced by macrophages play an important role in modulating plaque stability. More recently, the ADAMTS proteases, which are known to play a key role in the control of cartilage degradation during arthritis, have been found to be expressed in atherosclerotic lesions and suggested to have potentially important functions in the control of plaque stability. Unfortunately, the action of cytokines on the expression of ADAMTS family in macrophages is poorly understood. We have investigated the effect of classical cytokines (IFN-? and TGF-?) and those that have been recently identified (TL1A and IL-17) on the expression of ADAMTS-1, -4 and -5 in human macrophages. The expression of all three ADAMTS members was induced during differentiation of monocytes into macrophages. TGF-? had a differential action with induction of ADAMTS-1 and -5 expression and attenuation in the levels of ADAMTS-4. In contrast, IFN-? suppressed the expression of ADAMTS-1 without having an effect on ADAMTS-4 and -5. Although TL-1A or IL-17A alone had little effect on the expression of all the members, they induced their expression synergistically when present together. These studies provide new insight into the regulation of key ADAMTS family members in human macrophages by major cytokines in relation to atherosclerosis. PMID:23859810

  7. Marked Acceleration of Atherosclerosis following Lactobacillus casei induced Coronary Arteritis in a Mouse Model of Kawasaki Disease

    PubMed Central

    Chen, Shuang; Lee, Young Ho; Crother, Timothy R.; Fishbein, Michael; Zhang, Wenxuan; Yilmaz, Atilla; Shimada, Kenichi; Schulte, Danica J; Lehman, Thomas J.A.; Shah, Prediman K.; Arditi, Moshe

    2012-01-01

    Objective To investigate if Lactobacillus casei cell wall extract (LCWE)-induced Kawasaki Disease (KD) accelerates atherosclerosis in hypercholesterolemic mice. Method and Resuslts Apoe?/? or Ldlr?/? mice were injected with LCWE (KD mice) or PBS, fed high fat diet for 8 weeks, and atherosclerotic lesions in aortic sinuses (AS), arch (AC) and whole aorta were assessed. KD mice had larger, more complex aortic lesions with abundant collagen, and both extracellular and intracellular lipid and foam cells, compared to lesions in control mice despite similar cholesterol levels. Both Apoe?/? KD and Ldlr?/? KD mice showed dramatic acceleration in atherosclerosis vs. controls, with increases in en face aortic atherosclerosis and plaque size in both the AS and AC plaques. Accelerated atherosclerosis was associated with increased circulating IL-12p40, IFN-?, TNF-?, and increased macrophage, DC, and T cell recruitment in lesions. Furthermore, daily injections of the IL-1Ra, which inhibits LCWE induced KD vasculitis, prevented the acceleration of atherosclerosis. Conclusions Our results suggest an important pathophysiologic link between coronary arteritis/vasculitis in the KD mouse model and subsequent atherosclerotic acceleration, supporting the concept that a similar relation may also be present in KD patients. These results also suggest that KD in childhood may predispose to accelerated and early atherosclerosis as adults. PMID:22628430

  8. The dynamic lives of macrophage and dendritic cell subsets in atherosclerosis

    PubMed Central

    Taghavie-Moghadam, Paresa L.; Butcher, Matthew J.; Galkina, Elena V.

    2014-01-01

    Atherosclerosis, the major pathological process through which arterial plaques are formed, is a dynamic chronic inflammatory disease of large and medium sized arteries in which the vasculature, lipid metabolism, and the immune system all play integral roles. Both the innate and adaptive immune systems are involved in the development and progression of atherosclerosis but myeloid cells represent the major component of the burgeoning atherosclerotic plaque. Various myeloid cells, including monocytes, macrophages, and dendritic cells can be found within the healthy and atherosclerotic arterial wall, where they can contribute to or regulate inflammation. However, the precise behaviors and functions of these cells in situ are still active areas of investigation that continue to yield exciting and surprising new data. Here, we review recent progress in understanding of the complex biology of macrophages and dendritic cells, focusing particularly on the dynamic regulation of these subsets in the arterial wall and novel, emerging functions of these cells during atherogenesis. PMID:24628328

  9. Regulation of Atherosclerosis and Associated Risk Factors by Adenosine and Adenosine Receptors

    PubMed Central

    Koupenova, Milka; Johnston-Cox, Hillary; Ravid, Katya

    2013-01-01

    Adenosine is an endogenous metabolite that has an anti-inflammatory effect across the vasculature. Extracellular adenosine activates four G-protein coupled receptors (A1, A3, A2A, and A2B) whose expression varies in different cells and tissues, including the vasculature and blood cells. Higher levels of adenosine are generated during stress, inflammation, and upon tissue damage. Some of the adenosine receptors (AR), such as the A2BAR, are further upregulated following such stresses. This review will discuss the role of adenosine and adenosine receptors in the development of atherosclerosis and some of the risk factors associated with this pathology. These include adenosine receptor-regulated changes in atherosclerosis, blood pressure, thrombosis, and myocardial infarction. PMID:22850979

  10. The Expression and Functions of Toll-Like Receptors in Atherosclerosis

    PubMed Central

    Cole, Jennifer E.; Georgiou, Ektoras; Monaco, Claudia

    2010-01-01

    Inflammation drives atherosclerosis. Both immune and resident vascular cell types are involved in the development of atherosclerotic lesions. The phenotype and function of these cells are key in determining the development of lesions. Toll-like receptors are the most characterised innate immune receptors and are responsible for the recognition of exogenous conserved motifs on pathogens, and, potentially, some endogenous molecules. Both endogenous and exogenous TLR agonists may be present in atherosclerotic plaques. Engagement of toll-like receptors on immune and resident vascular cells can affect atherogenesis as signalling downstream of these receptors can elicit proinflammatory cytokine release, lipid uptake, and foam cell formation and activate cells of the adaptive immune system. In this paper, we will describe the expression of TLRs on immune and resident vascular cells, highlight the TLR ligands that may act through TLRs on these cells, and discuss the consequences of TLR activation in atherosclerosis. PMID:20652007

  11. 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

  12. 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

  13. Radiographic evidence of atherosclerosis of the descending aorta in a grey-cheeked parakeet (Brotogeris pyrrhopterus).

    PubMed

    Mans, Christoph; Brown, Cynthia J

    2007-03-01

    A 16-year-old male grey-cheeked parakeet (Brotogeris pyrrhopterus) was presented for dyspnea and decreased activity. The bird's diet was primarily table food, with a large proportion of animal products. Radiographs revealed a linear mineralized structure in the plane of the aorta and an enlarged hepatocardiac silhouette. Left atrial and left ventricular enlargement and a left ventricular systolic dysfunction were diagnosed by echocardiography. The bird's condition progressively declined, and it died 5 days after presentation. A postmortem examination revealed marked atherosclerosis of the aorta, great vessels of the heart, and coronary arteries with myocardial degeneration, pulmonary congestion, and ascites. Little is known about the risk factors of atherosclerosis in psittacine birds, and dietary influence, if any, is not understood. PMID:18069172

  14. The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques.

    PubMed

    van Gils, Janine M; Derby, Merran C; Fernandes, Luciana R; Ramkhelawon, Bhama; Ray, Tathagat D; Rayner, Katey J; Parathath, Sajesh; Distel, Emilie; Feig, Jessica L; Alvarez-Leite, Jacqueline I; Rayner, Alistair J; McDonald, Thomas O; O'Brien, Kevin D; Stuart, Lynda M; Fisher, Edward A; Lacy-Hulbert, Adam; Moore, Kathryn J

    2012-02-01

    Atherosclerotic plaque formation is fueled by the persistence of lipid-laden macrophages in the artery wall. The mechanisms by which these cells become trapped, thereby establishing chronic inflammation, remain unknown. Here we found that netrin-1, a neuroimmune guidance cue, was secreted by macrophages in human and mouse atheroma, where it inactivated the migration of macrophages toward chemokines linked to their egress from plaques. Acting via its receptor, UNC5b, netrin-1 inhibited the migration of macrophages directed by the chemokines CCL2 and CCL19, activation of the actin-remodeling GTPase Rac1 and actin polymerization. Targeted deletion of netrin-1 in macrophages resulted in much less atherosclerosis in mice deficient in the receptor for low-density lipoprotein and promoted the emigration of macrophages from plaques. Thus, netrin-1 promoted atherosclerosis by retaining macrophages in the artery wall. Our results establish a causative role for negative regulators of leukocyte migration in chronic inflammation. PMID:22231519

  15. Molecular imaging of atherosclerosis with nanoparticle-based fluorinated MRI contrast agents.

    PubMed

    Palekar, Rohun U; Jallouk, Andrew P; Lanza, Gregory M; Pan, Hua; Wickline, Samuel A

    2015-06-01

    As atherosclerosis remains one of the most prevalent causes of patient mortality, the ability to diagnose early signs of plaque rupture and thrombosis represents a significant clinical need. With recent advances in nanotechnology, it is now possible to image specific molecular processes noninvasively with MRI, using various types of nanoparticles as contrast agents. In the context of cardiovascular disease, it is possible to specifically deliver contrast agents to an epitope of interest for detecting vascular inflammatory processes, which serve as predecessors to atherosclerotic plaque development. Herein, we review various applications of nanotechnology in detecting atherosclerosis using MRI, with an emphasis on perfluorocarbon nanoparticles and fluorine imaging, along with theranostic prospects of nanotechnology in cardiovascular disease. PMID:26080701

  16. 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

  17. Agonistic antibody to angiotensin II type 1 receptor accelerates atherosclerosis in ApoE-/- mice

    PubMed Central

    Li, Weijuan; Chen, Yaoqi; Li, Songhai; Guo, Xiaopeng; Zhou, Wenping; Zeng, Qiutang; Liao, Yuhua; Wei, Yumiao

    2014-01-01

    This study aimed to investigate the effects of agonistic antibody to angiotensin II type 1 receptor (AT1-AA) on atherosclerosis in male ApoE-/- mice which were employed to establish the animal models of AT1-AA in two ways. In the first group, mice were injected subcutaneously with conjugated AT1 peptide at multiple sites; in the second group, mice were infused with AT1-AA prepared from rabbits that were treated with AT1 peptide intraperitoneally. Mice in each group were further randomly divided into five subgroups and treated with AT1 peptide/AT1-AA, AT1 peptide/AT1-AA plus valsartan, AT1 peptide/AT1-AA plus fenofibrate, AT1 peptide/ AT1-AA plus pyrrolidine dithiocarbamate (PDTC) and control vehicle, respectively. Antibodies were detected in mice (except for mice in control group). Aortic atherosclerotic lesions were assessed by oil red O staining, while plasma CRP, TNF-?, nuclear factor-kappa B (NF-?B) and H2O2 were determined by ELISA. CCR2 (the receptor of MCP-1), macrophages, and smooth muscle cells were detected by immunohistochemistry. P47phox, MCP-1 and eNOS were detected by RT-PCR, while P47phox, NF-?B and MCP-1 were detected by Western blot assay. The aortic atherosclerotic lesions were significantly increased in AT1 peptide/AT1-AA treated mice, along with simultaneous increases in inflammatory parameters. However, mice treated with valsartan, fenofibrate or PDTC showed alleviated progression of atherosclerosis and reductions in inflammatory parameters. Thus, AT1-AA may accelerate aortic atherosclerosis in ApoE-/- mice, which is mediated, at least in part, by the inflammatory reaction involving nicotinamide-adenine dinucleotide phosphate oxidase, reactive oxygen species, and NF-?B. In addition, valsartan, fenofibrate and PDTC may inhibit the AT1-AA induced atherosclerosis. PMID:25628779

  18. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure

    Microsoft Academic Search

    Peter Stenvinkel; Olof Heimbürger; Furcy Paultre; Ulf Diczfalusy; Tao Wang; Lars Berglund; Tomas Jogestrand

    1999-01-01

    Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure.BackgroundAtherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been

  19. Noninvasive Ultrasound Molecular Imaging of the Effect of Statins on Endothelial Inflammatory Phenotype in Early Atherosclerosis

    PubMed Central

    Khanicheh, Elham; Mitterhuber, Martina; Xu, Lifen; Haeuselmann, Stéphanie P.; Kuster, Gabriela M.; Kaufmann, Beat A.

    2013-01-01

    Background/Objectives Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) with contrast enhanced ultrasound (CEU) could assess treatment effects on endothelial phenotype in early atherosclerosis. Methods Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day). At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MBVCAM) and control microbubbles (MBCtr). Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression. Results Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MBVCAM in non-treated animals (MBVCAM 2±0.3 vs MBCtr 0.7±0.2, p<0.01), but not in statin-treated animals (MBVCAM 0.8±0.2 vs MBCtr 1.0±0.2, p?=?ns; p<0.01 for the effect of statin on MBVCAM signal). Conclusions Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients. PMID:23554922

  20. Analysis of haemodynamic factors involved in carotid atherosclerosis using computational fluid dynamics.

    PubMed

    Martin, D; Zaman, A; Hacker, J; Mendelow, D; Birchall, D

    2009-01-01

    Atherosclerosis presents a massive healthcare burden in both the developing and developed world. There is mounting evidence relating to the involvement of haemodynamic factors in the pathogenesis of this process. This article aims to review the current understandings that have developed in this area, and to present a demonstrative case study obtained using state of the art computational fluid dynamics (CFD) methodology to model and analyse haemodynamic factors within the atheromatous carotid artery bifurcation. PMID:20348534

  1. Relation between type a behavior pattern and the extent of coronary atherosclerosis in Japanese women

    Microsoft Academic Search

    Kouichi Yoshimasu; Masakazu Washio; Shoji Tokunaga; Keitaro Tanaka; Ying Liu; Hiroko Kodama; Hidekazu Arai; Samon Koyanagi; Koji Hiyamuta; Yoshitaka Doi; Tomoki Kawano; Osamu Nakagaki; Kazuyuki Takada; Shizuka Sasazuki; Takanobu Nii; Kazuyuki Shirai; Munehito Ideishi; Kikuo Arakawa; Masahiro Mohri; Akira Takeshita

    2002-01-01

    This study examined the relation of Type A behavior pattern and its components to angiographically documented coronary atherosclerosis\\u000a in 198 Japanese women. A questionnaire-based interview elicited psychosocial and other factors. Type A behavior pattern was\\u000a measured by 12 questions. Significant coronary stenosis was defined when a 75% or greater luminal narrowing occurred atoneor\\u000a more major coronary arteries or 50% or

  2. Proprotein convertases furin and PC5: targeting atherosclerosis and restenosis at multiple levels

    Microsoft Academic Search

    Philipp Stawowy; Eckart Fleck

    2005-01-01

    Several growth factors, chemokines, adhesion molecules, and proteolytic enzymes important for cell–cell\\/cell–matrix interactions in atherosclerosis and restenosis are initially synthesized as inactive precursor proteins. Activation of proproteins to biologically active molecules is regulated by limited endoproteolytic cleavage at dibasic amino acid residues. This type of activation typically requires the presence of suitable proprotein convertases (PCs). The PC-isozymes furin and PC5

  3. Erosive Hand Osteoarthritis is Associated with Subclinical Atherosclerosis and Endothelial Dysfunction

    PubMed Central

    Koutroumpas, Athanasios; Giannoukas, Athanasios; Zintzaras, Elias; Exarchou, Ekaterini; Baliakos, Aris; Makaritsis, Konstantinos; Sakkas, Lazaros I.

    2013-01-01

    Chronic inflammatory disorders have been associated with accelerated atherosclerosis and increased cardiovascular (CV) risk. Recent evidence suggests that erosive hand osteoarthritis (EOA) has considerable inflammation; therefore, we examined the presence of subclinical atherosclerosis and endothelial dysfunction in EOA. Twenty-four patients with EOA and 24 age- and sex-matched healthy individuals without clinical OA were included in the study. No subject had a history of CV disease. Intima-media thickness (IMT) and atheromatous plaques in the common carotid and common femoral arteries were measured by Doppler ultrasonography. The endothelium-dependent, flow-mediated dilatation (FMD) and endothelium-independent, sublingual glyceryl trinitrate (NTG)-induced dilatation (NMD) of the brachial artery were assessed. The EOA patients had significantly elevated systolic and diastolic blood pressure (p<0.001 for both). The 10-year risk of general CV disease, as predicted with the Framingham Risk Score, was similar in patients and controls (p=0.18). IMT of both common carotid and common femoral artery were increased in EOA (p=0.01 and p<0.01, respectively), but the frequency of atherosclerotic plaques was not increased. There was no difference in FMD and NMD between the two groups, but the difference between FMD and NMD was increased in EOA. In conclusion, this small controlled study showed an association between EOA and subclinical atherosclerosis that cannot be fully attributed to traditional CV risk factors, as assessed by the Framingham score. These results suggest that chronic, low-grade inflammation is implicated in atherosclerosis in EOA. PMID:24711757

  4. Preliminary Results of Intracranial Angioplasty for Vascular Stenosis Caused by Atherosclerosis and Vasculitis

    Microsoft Academic Search

    John D. McKenzie; Robert C. Wallace; Bruce L. Dean; Richard A. Flom; Mazen H. Khayata

    PURPOSE: To evaluate the results of balloon angioplasty of 17 stenoses resulting from intracranial atherosclerosis and vasculitis. METHODS: Seventeen skull-base and intracranial lesions were dilated with a microballoon angioplasty catheter.RESULTS:Initially, 16 of the 17 stenoses showed improvement at angiography. Moderate residual stenosis was found in 2 of 12 atherosclerotic lesions, both in the distal vertebral artery. Angioplasty in 1 of

  5. Does Early Mismatched Nutrition Predispose to Hypertension and Atherosclerosis, in Male Mice?

    PubMed Central

    Bol, Vanesa; Desjardins, Fanny; Reusens, Brigitte; Balligand, Jen-Luc; Remacle, Claude

    2010-01-01

    Background A link between early mismatched nutritional environment and development of components of the metabolic syndrome later in life has been shown in epidemiological and animal data. The aim of this study was to investigate whether an early mismatched nutrition produced by catch-up growth after fetal protein restriction could induce the appearance of hypertension and/or atherosclerosis in adult male mice. Methodology/Principal Findings Wild-type C57BL6/J or LDLr?/? dams were fed a low protein (LP) or a control (C) diet during gestation. Catch-up growth was induced in LP offspring by feeding dams with a control diet and by culling the litter to 4 pups against 8 in controls. At weaning, male mice were fed either standard chow or an obesogenic diet (OB), leading to 4 experimental groups. Blood pressure (BP) and heart rate (HR) were assessed in conscious unrestrained wild-type mice by telemetry. Atherosclerosis plaque area was measured in aortic root sections of LDLr?/? mice. We found that: (1) postnatal OB diet increased significantly BP (P<0.0001) and HR (P<0.008) in 3-month old OB-C and OB-LP offspring, respectively; (2) that maternal LP diet induced a significant higher BP (P<0.009) and HR (P<0.004) and (3) an altered circadian rhythm in addition to higher plasma corticosterone concentration in 9 months-old LP offspring; (4) that, although LP offspring showed higher plasma total cholesterol than control offspring, atherosclerosis assessed in aortic roots of 6-mo old mice featured increased plaque area due to OB feeding but not due to early mismatched nutrition. Conclusions/Significance These results indicate a long-term effect of early mismatched nutrition on the appearance of hypertension independently of obesity, while no effect on atherosclerosis was noticed at this age. PMID:20844591

  6. Monocyte Chemoattractant Protein1 Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice

    Microsoft Academic Search

    Robert J. Aiello; Patricia-Ann K. Bourassa; Saralyn Lindsey; Weifan Weng; Edward Natoli; Barrett J. Rollins; Patrice M. Milos

    2010-01-01

    The pro-inflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), plays a fundamental role in monocyte recruitment and has been implicated as a contributing factor to atherosclerosis. The predominant cell types within the vessel wall— endothelial cells, smooth muscle cells, and macrophages—all contribute to overexpression of MCP-1 in atherosclerotic tissue. In this report we assess the role of MCP-1 expression by leukocytes on

  7. Rapamune Does Not Attenuate High Cholesterol-Induced Atherosclerosis in Rabbits

    PubMed Central

    Attia, Ahmed; Ahmed, Mohamed; Ng, Siew Hon; Prasad, Kailash; Shoker, Ahmed

    2014-01-01

    Solid-organ transplant recipients are prone to develop atherosclerosis. The objectives of this study were to investigate the effects of Rapamune (Wyeth Canada, Saint-Larent, QC, Canada) on the rabbit model of atherosclerosis. The rabbits were assigned to four groups: group I, regular diet (control); group II, 1% cholesterol diet; group III, control with Rapamune (1 mg/kg/d orally); and group IV, high cholesterol diet with Rapamune. Blood samples for serum lipids (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C]), as well as malondialdehyde, and protein carbonyls, the indices of oxidative stress were collected at the end of 2 months on the respective diet regimen. Aortic tissue for atherosclerotic changes were also collected for oxidative stress indices were also collected. Rapamune reduced serum levels of TG, TC, LDL-C, and HDL-C. Rapamune elevated the oxidative stress in rabbits on high cholesterol diet. Rapamune did not attenuate extent of atherosclerosis (group II vs. group IV, 45.00?±?12.00 vs. 57.28?±?2.99%); intimal thickness (group II vs. group IV, 32.38?±?7.14?×?103 vs. 21.90?±?11.98?×?103 ?m2); intimal/medial ratio (group II vs. group IV, 0.50?±?0.06 vs. 0.35?±?0.06); and macrophage accumulation (group II vs. group IV, 69.72?±?5.02 vs. 61.52?±?8.94%) in the intima of rabbits on high cholesterol diet. The data suggest that (1) Rapamune increased the oxidative stress in rabbits on high cholesterol diet and (2) Rapamune did not attenuate the hypercholesterolemic atherosclerosis in the rabbit model. PMID:25075164

  8. Effect of crude extract of Bombyx mori coccoons in hyperlipidemia and atherosclerosis.

    PubMed

    Ali, Mir Mahdi; Arumugam, Sarasa Bharati A

    2011-04-01

    The silkworm is the larva or caterpillar of the domesticated silkmoth, Bombyx mori and being a primary producer of silk is an economically important insect. These days the silk is emerging as a resource for solving a broad range of biological problems. The silk (Abresham) is popularly known as Abresham muqriz (muqriz means cut) in Unani medicine. Its cocoons are extensively used as an ingredient of various Unani formulations like Khameer-E- Abresham Sada, Khameere Abresham Hakeem Arshad Wala, Khameere Abresham Ood Mastagi Wala etc. and are used to treat many cardiac and nervous disorders. The hypolipidemic activity of this drug, along with Nepata Hindostana (Badranjboya) and Terminalia Arjuna (Arjan) has been documented. But action of extract of Bombyx mori cocoons as a single drug is not documented. That's why; it was decided to study its effect on hyperlipidemia and atherosclerosis. The Male New Zealand White rabbits all of 1.5kgs were selected for the study. After stabilization period (2 weeks) the rabbits were divided into 3 groups (Group I - Control, Group II Lesion Control and Group III treated with extract of Bombyx mori silk cocoon). Hyperlipidemia and atherosclerosis were induced with 1% cholesterol diet. After induction of hyperlipidemia and atherosclerosis for twelve weeks, Group III rabbits were treated with Bombyx mori for 6 weeks (45 days). A significant decrease in hyperlipidemia was seen within 4 weeks of treatment. Histopathologically, the atherosclerotic plaques showed reduction in size. The third group showed a significant increase in the body weight and also an increase in the HDL cholesterol levels. The study concludes that extract of Bombyx mori cocoons has a significant effect on hypercholesterolemia and atherosclerosis probably because of its antioxidant and hypolipidemic effect. PMID:21760692

  9. Regulation and possible role of endocannabinoids and related mediators in hypercholesterolemic mice with atherosclerosis

    Microsoft Academic Search

    Fabrizio Montecucco; Isabel Matias; Sébastien Lenglet; Stefania Petrosino; Fabienne Burger; Graziano Pelli; Vincent Braunersreuther; François Mach; Sabine Steffens; Vincenzo Di Marzo

    2009-01-01

    In this study we analysed the possible modulation of endocannabinoids and related molecules during atherosclerosis development in mice. Wild-type and apolipoprotein E knockout (ApoE?\\/?) mice were fed either normal chow or high-cholesterol diet for 8–12 weeks, and tissue endocannabinoid levels were measured by liquid chromatography–mass spectrometry. We found increased levels of 2-AG in aortas and visceral adipose tissue (VAT) of

  10. Impact of Intracranial Cerebral Atherosclerosis on the Long-term Mortality after Ischemic Stroke

    Microsoft Academic Search

    Jihoon Kang; Yoonsook Jhang; Juneyoung Lee

    b Background: Intracranial cerebral atherosclerosis (ICAS) is an important cause of stroke, but it is not well-known whether and how much it contributes to the long-term prognosis of stroke patients. The purpose of this study was to elucidate the impact of ICAS on the long-term mortality of patients with acute ischemic stroke. Methods: From November 1998 to December 2002, a

  11. Inhibition of bone morphogenetic protein signaling reduces vascular calcification and atherosclerosis

    PubMed Central

    Derwall, Matthias; Malhotra, Rajeev; Lai, Carol S; Beppu, Yuko; Aikawa, Elena; Seehra, Jasbir S.; Zapol, Warren M; Bloch, Kenneth D.; Yu, Paul B.

    2012-01-01

    Objective The expression of bone morphogenetic proteins (BMPs) is enhanced in human atherosclerotic and calcific vascular lesions. While genetic gain- and loss-of-function experiments in mice have supported a causal role of BMP signaling in atherosclerosis and vascular calcification, it remains uncertain whether BMP signaling might be targeted pharmacologically to ameliorate both of these processes. Methods and Results We tested the impact of pharmacologic BMP inhibition upon atherosclerosis and calcification in low density lipoprotein receptor-deficient (LDLR?/?) mice. LDLR?/? mice fed a high-fat diet developed abundant vascular calcification within twenty weeks. Prolonged treatment of LDLR?/? mice with the small molecule BMP inhibitor LDN-193189 was well-tolerated and potently inhibited development of atheroma, as well as associated vascular inflammation, osteogenic activity, and calcification. Administration of recombinant BMP antagonist ALK3-Fc replicated the anti-atherosclerotic and anti-inflammatory effects of LDN-193189. Treatment of human aortic endothelial cells with LDN-193189 or ALK3-Fc abrogated the production of reactive oxygen species (ROS) induced by oxidized LDL, a known early event in atherogenesis. Unexpectedly, treatment of mice with LDN-193189 lowered LDL serum cholesterol by 35% and markedly decreased hepatosteatosis without inhibiting HMG-CoA reductase activity. Treatment with BMP2 increased, whereas LDN-193189 or ALK3-Fc inhibited apolipoprotein B100 secretion in HepG2 cells, suggesting that BMP signaling contributes to the regulation of cholesterol biosynthesis. Conclusions These results definitively implicate BMP signaling in atherosclerosis and calcification, while uncovering a previously unidentified role for BMP signaling in LDL cholesterol metabolism. BMP inhibition may be helpful in the treatment of atherosclerosis and associated vascular calcification. PMID:22223731

  12. Orthostatic Hypotension and Cognitive Function: The Atherosclerosis Risk in Communities Study

    Microsoft Academic Search

    Kathryn M. Rose; David Couper; Marsha L. Eigenbrodt; Thomas H. Mosley; A. Richey Sharrett; Rebecca F. Gottesman

    2010-01-01

    Background: To examine the association between orthostatic hypotension (OH) and cognitive function in middle-aged adults. Methods: Participants were 12,702 men and women from the Atherosclerosis Risk in Communities Study. OH was defined as decrease in systolic blood pressure (BP) by ?20 mm Hg or diastolic BP by ?10 mm Hg upon standing. At the 2nd and the 4th follow-up examinations,

  13. Race and Ethnic Variation in Excessive Daytime Sleepiness: The MultiEthnic Study of Atherosclerosis

    Microsoft Academic Search

    Kelly Glazer Baron; Kiang Liu; Cheeling Chan; Eyal Shahar; Romana Hasnain-Wynia; Phyllis Zee

    2010-01-01

    This cross-sectional study utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA). The sample included 5,173 older adults (mean age = 66.4 years) recruited from 6 field centers in the United States. Excessive daytime sleepiness (EDS) was evaluated using two measures: self-report of feeling excessively sleepy ? 5 days per month and the Epworth Sleepiness Scale (ESS) > 12. White

  14. Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome The Insulin Resistance Atherosclerosis Study (IRAS)

    Microsoft Academic Search

    Andreas Festa; George Howard; Leena Mykkanen; Russell P. Tracy; Steven M. Haffner

    2010-01-01

    Background—Inflammation has been suggested as a risk factor for the development of atherosclerosis. Recently, some components of the insulin resistance syndrome (IRS) have been related to inflammatory markers. We hypothesized that insulin insensitivity, as directly measured, may be associated with inflammation in nondiabetic subjects. Methods and Results—We studied the relation of C-reactive protein (CRP), fibrinogen, and white cell count to

  15. Association between Fibrinogen and Carotid Atherosclerosis According to Smoking Status in a Korean Male Population

    PubMed Central

    Cho, Hye Min; Kang, Dae Ryong; Oh, Sun Min; Kim, Byeong-Keuk; Suh, Il

    2015-01-01

    Purpose Although inconsistent, reports have shown fibrinogen levels to be associated with atherosclerosis. Accordingly, since cigarette smoking is associated with increased levels of fibrinogen and atherosclerosis, it may also affect the association between fibrinogen and atherosclerosis. We investigated the associations between fibrinogen and carotid intima-media thickness (IMT) according to smoking status in a Korean male population. Materials and Methods Plasma fibrinogen levels were measured in 277 men aged 40-87 years without a history of myocardial infarction or stroke. High-resolution B-mode ultrasonography was used to examine the common carotid arteries. IMT level was analyzed both as a continuous (IMT-max, maximum value; IMT-tpm, 3-point mean value) and categorical variable (higher IMT; presence of plaque). Serial linear and logistic regression models were employed to examine the association between fibrinogen and IMT according to smoking status. Results Fibrinogen levels were positively associated with IMT-max (standardized ?=0.25, p=0.021) and IMT-tpm (standardized ?=0.21, p=0.038), even after adjusting for age, body mass index, systolic blood pressure, fasting glucose, and total cholesterol to high-density lipoprotein cholesterol ratio in current smokers (n=75). No significant association between fibrinogen and IMT, however, was noted in former smokers (n=80) or nonsmokers (n=122). Adjusted odds ratios (95% confidence interval) for having plaque per one standard deviation higher fibrinogen level were 2.06 (1.09-3.89) for current smokers, 0.68 (0.43-1.10) for former smokers, and 1.06 (0.60-1.87) for nonsmokers. Conclusion Our findings suggest that cigarette smoking may modify the association between fibrinogen and carotid atherosclerosis. Further studies are required to confirm this finding in different populations. PMID:26069112

  16. 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

  17. Effects of Lycopene on the Initial State of Atherosclerosis in New Zealand White (NZW) Rabbits

    Microsoft Academic Search

    Mario Lorenz; Mandy Fechner; Janine Kalkowski; Kati Fröhlich; Anne Trautmann; Volker Böhm; Gerhard Liebisch; Stefan Lehneis; Gerd Schmitz; Antje Ludwig; Gert Baumann; Karl Stangl; Verena Stangl

    2012-01-01

    BackgroundLycopene is the main carotenoid in tomatoes, where it is found in high concentrations. Strong epidemiological evidence suggests that lycopene may provide protection against cardiovascular diseases. We therefore studied the effects of lycopene on diet-induced increase in serum lipid levels and the initiation of atherosclerosis in New Zealand White (NZW) rabbits.Methodology\\/Principal FindingsThe animals, divided into four groups of 9 animals

  18. Reduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid

    Microsoft Academic Search

    K. Prasad; S. V. Mantha; A. D. Muir; N. D. Westcott

    1998-01-01

    Flaxseed (Type I flaxseed) with 51–55% ?-linolenic acid in its oil and richest source of plant lignans, has been shown to reduce hypercholesterolemic atherosclerosis by 46% without lowering serum lipids. Antiatherogenic activity was claimed to be due to its ?-linolenic acid and\\/or lignan content. If ?-linolenic acid component of flaxseed is responsible for antiatherogenic activity, then, CDC-flaxseed (Type II flaxseed)

  19. Carotid atherosclerosis in women with polycystic ovary syndrome: Initial results from a case-control study

    Microsoft Academic Search

    David S. Guzick; Evelyn O. Talbott; Kim Sutton-Tyrrell; Holly C. Herzog; Lewis H. Kuller; Sidney K. Wolfson

    1996-01-01

    OBJECTIVE: Our purpose was to determine whether women with polycystic ovary syndrome have greater subclinical atherosclerosis as measured by carotid artery ultrasonography. STUDY DESIGN: Sixteen premenopausal women ?40 years old with a history of clinical polycystic ovary syndrome and a current total testosterone concentration ?2.0 nmol\\/L and 16 age-matched (±5 years) cycling women underwent carotid scanning. Intima-media thickness and plaque

  20. Autoantibodies against MDA-LDL in subjects with severe and minor atherosclerosis and healthy population controls

    Microsoft Academic Search

    Roland Steyger; Geert van Poppel; Jolanda M. A. Boer; Dick A. C. M. Kruijssen; Jacob C. Seidell; Hans M. G. Princen

    1996-01-01

    Autoantibodies against oxidized low-density lipoprotein (LDL) have been reported to be associated with atherosclerosis. However, data are not consistent.We compared the titres of autoantibodies to malondialdehyde-modified LDL in three groups, a case group with angiographically documented severe coronary stenosis (>80% stenosis in at least 1 vessel, n = 47), a hospital control group with minor stenosis on the coronary angiography

  1. Effect of macrophage ApoE on atherosclerosis in LDL-receptor deficient mice

    Microsoft Academic Search

    Carsten Tennert; Daniel Teupser; Marc A. Mueller; Wolfgang Wilfert; Ingrid Renner-Müller; Olga Stein; Yechezkiel Stein; Albrecht E. Sippel; Eckhard Wolf; Joachim Thiery

    2007-01-01

    Apolipoprotein E (ApoE) plays an important role in the development of atherosclerosis. Previous studies provide evidence for an atheroprotective role of ApoE in mouse models on the ApoE deficient (ApoE?\\/?) background. However, it is not clear whether this is also true on the LDL-receptor deficient (LDLR?\\/?) background. Transgenic mice carrying hApoE coding sequences in a chicken lysozyme expression cassette were

  2. Alcohol Consumption and Carotid Atherosclerosis in Older Adults The Cardiovascular Health Study

    Microsoft Academic Search

    Kenneth J. Mukamal; Richard A. Kronmal; Murray A. Mittleman; Daniel H. O'Leary; Joseph F. Polak; Mary Cushman; David S. Siscovick

    2010-01-01

    Objective—The association of alcohol use with atherosclerosis is inconsistent in previous studies. Methods and Results—For the Cardiovascular Health Study, 5888 adults aged 65 years and older underwent a standardized interview and examination. They reported beer, wine, and liquor use individually and underwent B-mode ultrasonog- raphy to determine internal and common carotid intima-media thickness (IMT). We compared composite carotid IMT values

  3. Tortuosity, Kinking, and Coiling of the Carotid Artery: Expression of Atherosclerosis or Aging?

    Microsoft Academic Search

    Laura Del Corso; Daniela Moruzzo; Biagio Conte; Maria Agelli; Anna Maria Romanelli; Fabrizio Pastine; Mariangela Protti; Ferdinando Pentimone; Giovanni Baggiani

    1998-01-01

    The etiology of carotid abnormalities is both congenital than acquired. The aim of this study was to clarify the role of aging and atherosclerosis in the acquired cases, and the role of these abnormalities in hemodynamic alterations and neurologic symptoms.Over a 1-year period the authors studied all the subjects undergoing carotid exami nation by continuous-wave and color-coded Doppler sonography at

  4. Atherosclerosis associated with vasculopathic lesions in a golden retriever with hypercholesterolemia

    PubMed Central

    Boynosky, Nicole A.; Stokking, Laura

    2014-01-01

    A 2-year-old neutered male golden retriever dog presented for lameness secondary to ulcerations of multiple digital paw pads was diagnosed with vasculitis and hypercholesterolemia. Despite treatment, ischemic necrosis progressed to include all distal extremities and the dog eventually expired due to myocardial infarction secondary to severe atherosclerosis. The rapid demise and the dermatologic lesions may have been secondary to cholesterol embolism syndrome which has never before been reported in a dog. PMID:24790237

  5. The role of non-LDL:non-HDL particles in atherosclerosis

    Microsoft Academic Search

    Jere P. Segrest

    2002-01-01

    Elevated concentrations of circulating apolipoprotein B (apoB)-containing lipoproteins, other than low-density lipoprotein\\u000a (LDL), have been implicated as causative agents for the development of atherosclerosis. A form of dyslipidemia, the atherogenic\\u000a lipoprotein profile, that consists of elevated intermediate-density lipoprotein (IDL), triglycerides (TGs), dense LDL and\\u000a dense very low density lipoprotein (VLDL), and low high density lipoprotein-2, occurs in 40% to 50%

  6. Small dense low-density lipoprotein cholesterol concentration and carotid atherosclerosis

    Microsoft Academic Search

    Tetsuo Shoji; Sawako Hatsuda; Shoko Tsuchikura; Kayo Shinohara; Eiji Kimoto; Hidenori Koyama; Masanori Emoto; Yoshiki Nishizawa

    2009-01-01

    Low-density lipoprotein cholesterol (LDL-C) and the small dense LDL (SdLDL) phenotype are both predictors for ischemic heart disease. We examined whether cholesterol of SdLDL (SdLDL-C) is more closely associated with carotid artery intima-media thickness (CA-IMT), a surrogate measure of atherosclerosis, than LDL-C and other lipid parameters. The subjects were 326 consecutive participants including those with dyslipidemia, diabetes mellitus, hypertension, chronic

  7. Cholesterol-Induced Non-Alcoholic Fatty Liver Disease and Atherosclerosis Aggravated by Systemic Inflammation

    PubMed Central

    Seo, Hong Seog; Lee, Yong Jik; Kim, Hyun Hee; Son, Hyun-Hwa; Choi, Man Ho

    2014-01-01

    Although triglyceride accumulation in the liver causes non-alcoholic fatty liver disease (NAFLD), hypercholesterolemia is also a main cause of NAFLD as well as atherosclerosis. However, NAFLD and atherosclerosis have not been investigated simultaneously in animal models fed a high-cholesterol diet. Moreover, it is unclear whether systemic inflammation can exacerbate both pathologies in the same model. Accordingly, this study investigated the effect of additional systemic inflammation on NAFLD and atherosclerosis induced by cholesterol overload in wild animals. New Zealand white rabbits were divided into 4 groups: groups I (control) and II received normal chow, and groups III and IV received a 1% cholesterol diet. To induce inflammation via toll-like receptor (TLR)-4 signaling, groups II and IV received subcutaneous injections of 0.5 mL of 1% carrageenan every 3 weeks. After 3 months, total cholesterol markedly increased in groups III and IV, and the serum expressions of systemic inflammatory markers were elevated in the groups II–IV. Early NAFLD lesions (e.g., mild fatty changes in the liver with sporadic fibrosis) and atherosclerosis (e.g., intimal hyperplasia composed of foam cells) were observed in both the liver and aorta specimens from group III, and advanced lesions were observed in group IV. The expressions of inflammatory cellular receptors, TLR-2 and TLR-4, in the aorta gradually increased from group I to IV but were similar in the liver in groups II–IV. Cholesteryl ester (CE) levels were higher in group IV than in group III, although the difference was not significant. CE levels in the aorta were similar between groups III and IV. Systemic inflammation can simultaneously exacerbate existing early lesions due to cholesterol overload in both the liver and aorta of rabbits. However, the cellular response of inflammatory receptors and expression of cholesterol metabolites differ between these organs. PMID:24901254

  8. Preventive effect of trifluoperazine on atherosclerosis induced by cholesterol & adrenaline in rabbits.

    PubMed

    Mohindroo, A; Kukreja, R S; Kaul, D

    1989-06-01

    Studies on the preventive role of trifluoperazine on cholesterol and adrenaline-induced experimental atherosclerosis in rabbits, revealed that trifluoperazine completely prevented the development of atherosclerotic lesions in both the aorta and coronary arteries of animals administered atherogenic diet and adrenaline (im) despite the fact that this drug had no significant effect on the elevated serum lipid profile induced by atherogenic diet. These findings confirm earlier observations of the authors that trifluoperazine has an inherent capacity to prevent atherogenesis. PMID:2767746

  9. Expression of Neutrophil Gelatinase-Associated Lipocalin in Atherosclerosis and Myocardial Infarction

    Microsoft Academic Search

    Anne-Louise Hemdahl; Anders Gabrielsen; Chaoyong Zhu; Per Eriksson; Ulf Hedin; Jens Kastrup; Peter Thoren; Goran K. Hansson

    2010-01-01

    Objective—Neutrophil gelatinase-associated lipocalin (NGAL) modulates the activity of matrix metalloproteinase (MMP) 9, an important mediator of vascular remodeling and plaque instability in atherosclerosis. This study aimed to analyze the expression of NGAL in atherosclerotic plaques and myocardial infarction (MI). Methods and Results—Atherosclerotic apolipoprotein E (apoE)\\/ low-density lipoprotein receptor (LDLR)\\/ and C57BL\\/6J control mice were exposed to brief hypoxic stress (10

  10. Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice

    Microsoft Academic Search

    B Geeraert; F Crombé; M Hulsmans; N Benhabilès; J M Geuns; P Holvoet

    2010-01-01

    Objective:Stevioside is a non-caloric natural sweetener that does not induce a glycemic response, making it attractive as sweetener to diabetics and others on carbohydrate-controlled diets. Obesity is frequently associated with insulin resistance and increased inflammation and oxidative stress. Therefore, we investigated its effects on insulin resistance, inflammation and oxidative stress related to atherosclerosis in obese insulin-resistant mice.Research design:Twelve-week-old mice were

  11. Hand osteoarthritis in older women is associated with carotid and coronary atherosclerosis: the AGES Reykjavik study

    Microsoft Academic Search

    H Jonsson; G P Helgadottir; T Aspelund; G Eiriksdottir; S Sigurdsson; T Ingvarsson; T B Harris; L Launer; V Gudnason

    2009-01-01

    Objective:There is evidence that atherosclerosis may contribute to the initiation or progression of osteoarthritis. To test this hypothesis, the presence and severity of hand osteoarthritis (HOA) was compared with markers of atherosclerotic vascular disease in an elderly population.Patients and Methods:The AGES Reykjavik Study is a population-based multidisciplinary study of ageing in the elderly population of Reykjavik. In a study of

  12. Does Statin Therapy Affect the Progression of Atherosclerosis Measured by a Coronary Calcium Score?

    Microsoft Academic Search

    Edward A. Gill Jr

    2010-01-01

    Coronary atherosclerosis is a leading cause of death in the United States and worldwide, accounting for close to 1 million\\u000a deaths annually in the United States alone. The evaluation of coronary disease by CT-derived calcium scores is a rapidly evolving\\u000a field of medical imaging. Furthermore, until recently, whether or not regression or progression of coronary disease could\\u000a accurately be assessed

  13. 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

  14. Prospective study of particulate air pollution exposures, subclinical atherosclerosis, and clinical cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

    PubMed

    Kaufman, Joel D; Adar, Sara D; Allen, Ryan W; Barr, R Graham; Budoff, Matthew J; Burke, Gregory L; Casillas, Adrian M; Cohen, Martin A; Curl, Cynthia L; Daviglus, Martha L; Diez Roux, Ana V; Jacobs, David R; Kronmal, Richard A; Larson, Timothy V; Liu, Sally Lee-Jane; Lumley, Thomas; Navas-Acien, Ana; O'Leary, Daniel H; Rotter, Jerome I; Sampson, Paul D; Sheppard, Lianne; Siscovick, David S; Stein, James H; Szpiro, Adam A; Tracy, Russell P

    2012-11-01

    The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) was initiated in 2004 to investigate the relation between individual-level estimates of long-term air pollution exposure and the progression of subclinical atherosclerosis and the incidence of cardiovascular disease (CVD). MESA Air builds on a multicenter, community-based US study of CVD, supplementing that study with additional participants, outcome measurements, and state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, and black carbon. More than 7,000 participants aged 45-84 years are being followed for over 10 years for the identification and characterization of CVD events, including acute myocardial infarction and other coronary artery disease, stroke, peripheral artery disease, and congestive heart failure; cardiac procedures; and mortality. Subcohorts undergo baseline and follow-up measurements of coronary artery calcium using computed tomography and carotid artery intima-medial wall thickness using ultrasonography. This cohort provides vast exposure heterogeneity in ranges currently experienced and permitted in most developed nations, and the air monitoring and modeling methods employed will provide individual estimates of exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand and reduce uncertainty in health effect estimation regarding long-term exposure to air pollution and CVD. PMID:23043127

  15. 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.

  16. 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

  17. 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

  18. Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits.

    PubMed

    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

  19. Interferon-? promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis

    PubMed Central

    Denny, Michael F.; Thacker, Seth; Mehta, Hemal; Somers, Emily C.; Dodick, Todd; Barrat, Franck J.; McCune, W. Joseph

    2007-01-01

    Individuals with systemic lupus erythematosus (SLE) have a striking increase in premature atherosclerosis of unclear etiology. Accelerated endothelial cell apoptosis occurs in SLE and correlates with endothelial dysfunction. Endothelial progenitor cells (EPCs) and myelomonocytic circulating angiogenic cells (CACs) are crucial in blood vessel repair after vascular damage, and decreased levels or abnormal function of EPCs/CACs are established atherosclerosis risk factors. We investigated if vascular repair is impaired in SLE. We report that SLE patients display abnormal phenotype and function of EPCs/CACs. These abnormalities are characterized by significant decreases in the number of circulating EPCs (310 ± 50 EPCs/mL of blood in SLE versus 639 ± 102 in controls) and significant impairments in the capacity of EPCs/CACs to differentiate into mature ECs and synthesize adequate levels of the proangiogenic molecules vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF). These abnormalities are triggered by interferon-? (IFN-?), which induces EPC and CAC apoptosis and skews myeloid cells toward nonangiogenic phenotypes. Lupus EPCs/CACs have increased IFN-? expression and their supernatants promote higher induction of IFN-inducible genes. Importantly, neutralization of IFN pathways restores a normal EPC/CAC phenotype in lupus. SLE is characterized by an imbalance between endothelial cell damage and repair triggered by type I IFNs, which might promote accelerated atherosclerosis. PMID:17638846

  20. 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.