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1

Suppressive Effects of Irbesartan on Inflammation and Apoptosis in Atherosclerotic Plaques of apoE?/? Mice: Molecular Imaging with 14C-FDG and 99mTc-Annexin A5  

PubMed Central

Objectives To investigate the effects of irbesartan on inflammation and apoptosis in atherosclerotic plaques by histochemical examination and molecular imaging using 14C-FDG and 99mTc-annexin A5. Background Irbesartan has a peroxisome proliferator-activated receptor gamma (PPAR?) activation property in addition to its ability to block the AT1 receptor. Accordingly, irbesartan may exert further anti-inflammatory and anti-apoptotic effects in atherosclerotic plaques. However, such effects of irbesartan have not been fully investigated. Molecular imaging using 18F-FDG and 99mTc-annexin A5 is useful for evaluating inflammation and apoptosis in atherosclerotic plaques. Methods Female apoE?/? mice were treated with irbesartan-mixed (50 mg/kg/day) or irbesartan-free (control) diet for 12 weeks (n?=?11/group). One week after the treatment, the mice were co-injected with 14C-FDG and 99mTc-annexin A5, and cryostat sections of the aortic root were prepared. Histochemical examination with Movat's pentachrome (plaque size), Oil Red O (lipid deposition), Mac-2 (macrophage infiltration), and TUNEL (apoptosis) stainings were performed. Dual-tracer autoradiography was carried out to evaluate the levels of 14C-FDG and 99mTc-annexin A5 in plaques (%ID×kg). In vitro experiments were performed to investigate the mechanism underlying the effects. Results Histological examination indicated that irbesartan treatment significantly reduced plaque size (to 56.4%±11.1% of control), intra-plaque lipid deposition (53.6%±20.2%) and macrophage infiltration (61.9%±20.8%) levels, and the number of apoptotic cells (14.5%±16.6%). 14C-FDG (43.0%±18.6%) and 99mTc-annexin A5 levels (45.9%±16.8%) were also significantly reduced by irbesartan treatment. Irbesartan significantly suppressed MCP-1 mRNA expression in TNF-? stimulated THP-1 monocytes (64.8%±8.4% of un-treated cells). PPAR? activation was observed in cells treated with irbesartan (134%±36% at 3 µM to 3329%±218% at 81 µM) by a PPAR? reporter assay system. Conclusions Remissions of inflammation and apoptosis as potential therapeutic effects of irbesartan on atherosclerosis were observed. The usefulness of molecular imaging using 18F-FDG and 99mTc-annexin A5 for evaluating the therapeutic effects of irbesartan on atherosclerosis was also suggested. PMID:24586699

Zhao, Songji; Kobayashi, Tatsuo; Fukao, Keita; Tanaka, Yoshikazu; Nakano, Toru; Yoshida, Tetsuya; Takemoto, Hiroshi; Tamaki, Nagara; Kuge, Yuji

2014-01-01

2

Atherosclerosis  

MedlinePLUS

Atherosclerosis Updated:May 12,2014 View an animation of atherosclerosis Atherosclerosis, or hardening of the arteries, is ... the arteries as you get older. How does atherosclerosis start and progress? It's a complex process. Exactly ...

3

Suppression of high lipid diet induced by atherosclerosis sarpogrelate  

PubMed Central

Sarpogrelate (SP), a serotonin (5-HT2A) receptor antagonist, is used as an anti-platelet agent for the treatment of some vascular diseases. SP has been reported to inhibit 5-HT induced coronary artery spasm, increase in intracellular calcium and smooth muscle cells proliferation. This study was undertaken to test that SP suppresses the development of atherosclerosis due to high cholesterol diet (HCD) by decreasing blood viscosity and oxidative stress. For this purpose, 29 rabbits were divided into four groups: control group (normal diet); normal diet group with SP at the dose of 5 mg/kg/day; HCD group fed 1% cholesterol; and HCD group with SP at the dose of 5 mg/kg/day. After 90 days of the experiment, blood samples were collected and the animals were killed; the thoracic aorta was stained by the Oil Red O staining method. The results indicate that plasma levels of cholesterol, triglycerides and malondialdehyde were increased in rabbits fed HCD. Plasma viscosity and whole blood viscosity were also higher in the HCD group than that in normal diet group. Treatment with SP prevented these alterations induced by HCD whereas this agent had no significant effect in rabbits fed normal diet. Morphological examination of the aorta revealed that SP treatment prevented the formation of foam cells and atherosclerotic plaque. It is suggested that the beneficial effects of SP in atherosclerosis may be due to actions on blood viscosity, lipid levels and oxidative stress. PMID:22348587

Xu, Yan-Jun; Zhang, Ming; Ji, Lei; Elimban, Vijayan; Chen, Li; Dhalla, Naranjan S

2012-01-01

4

PPAR? regulates multiple proinflammatory pathways to suppress atherosclerosis  

PubMed Central

Lipid homeostasis and inflammation are key determinants in atherogenesis, exemplified by the requirement of lipid-laden, foam cell macrophages for atherosclerotic lesion formation. Although the nuclear receptor PPAR? has been implicated in both systemic lipid metabolism and macrophage inflammation, its role as a therapeutic target in vascular disease is unclear. We show here that orally active PPAR? agonists significantly reduce atherosclerosis in apoE?/? mice. Metabolic and gene expression studies reveal that PPAR? attenuates lesion progression through its HDL-raising effect and anti-inflammatory activity within the vessel wall, where it suppresses chemoattractant signaling by down-regulation of chemokines. Activation of PPAR? also induces the expression of regulator of G protein signaling (RGS) genes, which are implicated in blocking the signal transduction of chemokine receptors. Consistent with this, PPAR? ligands repress monocyte transmigration and macrophage inflammatory responses elicited by atherogenic cytokines. These results reveal that PPAR? antagonizes multiple proinflammatory pathways and suggest PPAR?-selective drugs as candidate therapeutics for atherosclerosis. PMID:18337509

Barish, Grant D.; Atkins, Annette R.; Downes, Michael; Olson, Peter; Chong, Ling-Wa; Nelson, Mike; Zou, Yuhua; Hwang, Hoosang; Kang, Heonjoong; Curtiss, Linda; Evans, Ronald M.; Lee, Chih-Hao

2008-01-01

5

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

SciTech Connect

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.

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

6

Suppression of experimental atherosclerosis by the Ca++-antagonist lanthanum. Possible role of calcium in atherogenesis.  

PubMed Central

Agents inhibiting calcium deposition into arteries are known to suppress atherosclerosis in animals. However, the precise role of calcium in atherogenesis is unknown. In this study, the specific Ca2+-antagonist lanthanum was used to attempt suppression of experimental atherosclerosis and to gain more insight into the possible effects of calcium on atherogenesis. Rabbits were fed an atherogenic diet with and without increasing doses of LaCl3. All cholesterol-fed rabbits showed marked increases in serum cholesterol and ca2+. Untreated atherogenic animals revealed pronounced gross and microscopic atherosclerosis and striking increases in the aortic content of cholesterol, collagen, "elastin," and calcium as well as of elastin calcium, polar amino acids, and cholesterol. With increasing LaCl3 dosage these abnormalities progressively decreased and were completely abolished at the highest dose. The ingested La3+ was absorbed only in small quantities and had no discernible effect on the calcium and connective tissue content of bone, skin, lung, heart, and skeletal muscle nor on myocardial function (left ventricle pressure and left ventricle dp/dt) or myocardial and muscle content in ATP and creatine phosphate. The data suggest that shifts in arterial Ca2+-distribution may play a decisive part in atherogenesis, and provision of arterial calcium homeostasis by La3+ a pivotal role in its prevention, despite hypercholesteremia. Other inhibitors of calcium deposition into arteries may exert their protective effect by similar mechanisms. However, a direct inhibition of atherogenesis by La3+ cannot entirely be ruled out in this study, although no direct effects of La3+ on tissue metabolism have as yet been reported. Images PMID:7364947

Kramsch, D M; Aspen, A J; Apstein, C S

1980-01-01

7

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

PubMed Central

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

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

8

Inhibiting DNA Methylation by 5-Aza-2'-deoxycytidine ameliorates atherosclerosis through suppressing macrophage inflammation.  

PubMed

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

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

2014-12-01

9

Irbesartan ameliorates diabetic cardiomyopathy by regulating protein kinase D and ER stress activation in a type 2 diabetes rat model.  

PubMed

Recent studies demonstrate an important role of protein kinase D (PKD) in the cardiovascular system. However, the potential role of PKD in the pathogenesis of diabetic cardiomyopathy (DCM) remains unclear. Irbesartan has beneficial effects against diabetes-induced heart damage, while the mechanisms were still poorly understood. Our present study was designed to investigate the effects of irbesartan in DCM and whether the cardioprotective effects of irbesartan were mediated by PKD and endoplasmic reticulum (ER) stress. We induced the type 2 diabetic rat model by high fat diet and low dose streptozotocin injection. The characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. 8-weeks administration of irbesartan (15, 30 and 45mg/kg/day) was used to evaluate the effect irbesartan in DCM. Diabetic rats revealed severe metabolic abnormalities, left ventricular dysfunction, myocardial fibrosis and apoptosis. PKD and ER stress were excessive activated in the myocardium of diabetic rats. Furthermore, cardiac fibrosis, apoptosis, diastolic dysfunction and ER stress were all significantly related to PKD activation in diabetic rats. Irbesartan treatment attenuated the activation of PKD and ER stress, which paralleled its cardioprotective effects. Our study suggests that irbesartan could ameliorate cardiac remodeling and dysfunction in type 2 diabetes, and these beneficial effects were associated with its ability to suppress the activation of PKD and ER stress. PMID:25617729

Liu, Xiangjuan; Xu, Qun; Wang, Xiaomeng; Zhao, Zhuo; Zhang, Liping; Zhong, Ling; Li, Li; Kang, Weiqiang; Zhang, Yun; Ge, Zhiming

2015-03-01

10

MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1  

PubMed Central

Atherosclerosis, a hyperlipidemia-induced chronic inflammatory process of the arterial wall, develops preferentially at sites where disturbed laminar flow compromises endothelial cell (EC) function. Here we show that endothelial miR-126-5p maintains a proliferative reserve in ECs through suppression of the Notch1 inhibitor delta-like 1 homolog (Dlk1) and thereby prevents atherosclerotic lesion formation. Endothelial recovery after denudation was impaired in Mir126?/? mice because lack of miR-126-5p, but not miR-126-3p, reduced EC proliferation by derepressing Dlk1. At nonpredilection sites, high miR-126-5p levels in endothelial cells confer a proliferative reserve that compensates for the antiproliferative effects of hyperlipidemia, such that atherosclerosis was exacerbated in Mir126?/? mice. In contrast, downregulation of miR-126-5p by disturbed flow abrogated EC proliferation at predilection sites in response to hyperlipidemic stress through upregulation of Dlk1 expression. Administration of miR-126-5p rescued EC proliferation at predilection sites and limited atherosclerosis, introducing a potential therapeutic approach. PMID:24584117

Schober, Andreas; Nazari-Jahantigh, Maliheh; Wei, Yuanyuan; Bidzhekov, Kiril; Gremse, Felix; Grommes, Jochen; Megens, Remco T A; Heyll, Kathrin; Noels, Heidi; Hristov, Michael; Wang, Shusheng; Kiessling, Fabian; Olson, Eric N; Weber, Christian

2015-01-01

11

Silence of NLRP3 Suppresses Atherosclerosis and Stabilizes Plaques in Apolipoprotein E-Deficient Mice  

PubMed Central

Objectives. The role of the NLRP3 inflammasome in atherosclerosis remains controversial. The aim of this study was to determine whether inhibition of NLRP3 signaling by lentivirus-mediated RNA interference could reduce atherosclerosis and stabilizes plaques. We also tried to explore the mechanisms of the impact of NLRP3 inflammasome on atherosclerosis. Methods. Apolipoprotein E-deficient mice aged 8 weeks were fed a high-fat diet and were injected with NLRP3 interfering or mock viral suspension after 4 weeks. Lentivirus transfer was repeated in 2 weeks. Four weeks after the first lentivirus injection, we evaluated the effects of NLRP3 gene silencing on plaque composition and stability and on cholesterol efflux and collagen metabolism, by histopathologic analyses and real-time PCR. Results. Gene silence of NLRP3 prevented plaques progression and inhibited inductions of proinflammatory cytokines. Moreover, this RNA interference reduced plaque content of macrophages and lipid, and increased plaque content of smooth muscle cells and collagen, leading to the stabilizing of atherosclerotic plaques. Conclusions. NLRP3 inflammasomes may play a vital role in atherosclerosis, and lentivirus-mediated NLRP3 silencing would be a new strategy to inhibit plaques progression and to reduce local inflammation. PMID:24999295

Zheng, Fei; Xing, Shanshan; Gong, Zushun; Mu, Wei; Xing, Qichong

2014-01-01

12

Inhibition of Nuclear Factor of Activated T-Cells (NFAT) Suppresses Accelerated Atherosclerosis in Diabetic Mice  

PubMed Central

Objective of the Study Diabetic patients have a much more widespread and aggressive form of atherosclerosis and therefore, higher risk for myocardial infarction, peripheral vascular disease and stroke, but the molecular mechanisms leading to accelerated damage are still unclear. Recently, we showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin. Here we investigate whether NFAT activation may be a link between diabetes and atherogenesis. Methodology and Principal Findings Streptozotocin (STZ)-induced diabetes in apolipoprotein E?/? mice resulted in 2.2 fold increased aortic atherosclerosis and enhanced pro-inflammatory burden, as evidenced by elevated blood monocytes, endothelial activation- and inflammatory markers in aorta, and pro-inflammatory cytokines in plasma. In vivo treatment with the NFAT blocker A-285222 for 4 weeks completely inhibited the diabetes-induced aggravation of atherosclerosis, having no effect in non-diabetic mice. STZ-treated mice exhibited hyperglycemia and higher plasma cholesterol and triglycerides, but these were unaffected by A-285222. NFAT-dependent transcriptional activity was examined in aorta, spleen, thymus, brain, heart, liver and kidney, but only augmented in the aorta of diabetic mice. A-285222 completely blocked this diabetes-driven NFAT activation, but had no impact on the other organs or on splenocyte proliferation or cytokine secretion, ruling out systemic immunosuppression as the mechanism behind reduced atherosclerosis. Instead, NFAT inhibition effectively reduced IL-6, osteopontin, monocyte chemotactic protein 1, intercellular adhesion molecule 1, CD68 and tissue factor expression in the arterial wall and lowered plasma IL-6 in diabetic mice. Conclusions Targeting NFAT signaling may be a novel and attractive approach for the treatment of diabetic macrovascular complications. PMID:23755169

Zetterqvist, Anna V.; Berglund, Lisa M.; Blanco, Fabiana; Garcia-Vaz, Eliana; Wigren, Maria; Dunér, Pontus; Andersson, Anna-Maria Dutius; To, Fong; Spegel, Peter; Nilsson, Jan; Bengtsson, Eva; Gomez, Maria F.

2013-01-01

13

Suppressed soluble Fms-like tyrosine kinase-1 production aggravates atherosclerosis in chronic kidney disease.  

PubMed

Patients with chronic kidney disease (CKD) die of cardiovascular diseases for unknown reasons. Blood vessel formation in plaques and its relationship with plaque stability could be involved with signaling through the Flt-1 receptor and its ligands, vascular endothelial growth factor, and the closely related placental growth factor (PlGF). Flt-1 also exists as a circulating regulatory splice variant short-inhibitory form (sFlt-1) that serves as a decoy receptor, thereby inactivating PlGF. Heparin releases sFlt-1 by displacing the sFlt-1 heparin-binding site from heparin sulfate proteoglycans. Heparin could provide diagnostic inference or could also induce an antiangiogenic state. In the present study, postheparin sFlt-1 levels were lower in CKD patients than in control subjects. More importantly, sFlt-1 levels were inversely related to atherosclerosis in CKD patients, and this correlation was more robust after heparin injection, as verified by subsequent cardiovascular events. Knockout of apolipoprotein E (ApoE) and/or sFlt-1 showed that the absence of sFlt-1 worsened atherogenesis in ApoE-deficient mice. Thus, the relationship between atherosclerosis and PlGF signaling, as regulated by sFlt-1, underscores the underappreciated role of heparin in sFlt-1 release. These clinical and experimental data suggest that novel avenues into CKD-dependent atherosclerosis and its detection are warranted. PMID:24048373

Matsui, Masaru; Takeda, Yukiji; Uemura, Shiro; Matsumoto, Takaki; Seno, Ayako; Onoue, Kenji; Tsushima, Hideo; Morimoto, Katsuhiko; Soeda, Tsunenari; Okayama, Satoshi; Somekawa, Satoshi; Samejima, Ken-Ichi; Kawata, Hiroyuki; Kawakami, Rika; Nakatani, Kimihiko; Iwano, Masayuki; Saito, Yoshihiko

2014-02-01

14

Atherosclerosis induced by chronic inhibition of the synthesis of nitric oxide in moderately hypercholesterolaemic rabbits is suppressed by pitavastatin  

PubMed Central

Background and purpose: It is not clear if the new 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pitavastatin prevents atherogenesis by a direct effect. Statins have a cholesterol-lowering effect, so an accessible animal model of atherosclerosis showing only moderate hypercholesterolaemia as in humans, is needed. The effects of pitavastatin were evaluated on atherosclerotic lesions accumulating foam cells derived from macrophages, produced in rabbits with moderate hypercholesterolaemia by chronic inhibition of nitric oxide synthase (NOS). Experimental approach: White New Zealand rabbits were fed a 0.2% cholesterol diet with the NOS inhibitor N?-nitro-L-arginine methyl ester (L-NAME) in the same diet. Pitavastatin (0.1 and 0.3 mg·kg?1) was given orally once a day for 8 weeks. The aortic arch and thoracic aorta were analysed by histochemistry and atherosclerotic lesions were quantified. The effect of pitavastatin on adhesion of THP-1 cells to endothelial cells, and cholesterol content in RAW264.7 cells incubated with oxidized or acetylated LDL were also investigated. Key results: Atherosclerotic lesions containing foam cells were induced in a model of atherosclerosis in rabbits with moderate hypercholesterolaemia by chronic inhibition of NOS. The area of atherosclerotic lesions was diminished by pitavastatin administration. The adhesion of THP-1 cells and cholesteryl ester content in RAW macrophages were decreased by pitavastatin treatment. Conclusion: Atherosclerosis induced by chronic inhibition of NOS in moderately hypercholesterolaemic rabbits was suppressed by pitavastatin via inhibition of macrophage accumulation and macrophage foam cell formation. PMID:20233214

Kitahara, Masaki; Kanaki, Tatsuro; Ishii, Itsuko; Saito, Yasushi

2010-01-01

15

ATF3 protects against atherosclerosis by suppressing 25-hydroxycholesterol–induced lipid body formation  

PubMed Central

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipid-loaded macrophages in the arterial wall. We demonstrate that macrophage lipid body formation can be induced by modified lipoproteins or by inflammatory Toll-like receptor agonists. We used an unbiased approach to study the overlap in these pathways to identify regulators that control foam cell formation and atherogenesis. An analysis method integrating epigenomic and transcriptomic datasets with a transcription factor (TF) binding site prediction algorithm suggested that the TF ATF3 may regulate macrophage foam cell formation. Indeed, we found that deletion of this TF results in increased lipid body accumulation, and that ATF3 directly regulates transcription of the gene encoding cholesterol 25-hydroxylase. We further showed that production of 25-hydroxycholesterol (25-HC) promotes macrophage foam cell formation. Finally, deletion of ATF3 in Apoe?/? mice led to in vivo increases in foam cell formation, aortic 25-HC levels, and disease progression. These results define a previously unknown role for ATF3 in controlling macrophage lipid metabolism and demonstrate that ATF3 is a key intersection point for lipid metabolic and inflammatory pathways in these cells. PMID:22473958

Gold, Elizabeth S.; Ramsey, Stephen A.; Sartain, Mark J.; Selinummi, Jyrki; Podolsky, Irina; Rodriguez, David J.; Moritz, Robert L.

2012-01-01

16

Overexpression of STAMP2 suppresses atherosclerosis and stabilizes plaques in diabetic mice  

PubMed Central

Our research aims to evaluate the function of the STAMP2 gene, an important trigger in insulin resistance (IR), and explore its role in macrophage apoptosis in diabetic atherosclerotic vulnerable plaques. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. The level of STAMP2 was measured by RT-PCR and Western blot. The plaque area, lipid and collagen content of brachiocephalic artery plaques were measured by histopathological analyses, and the macrophage apoptosis was measured by TUNEL. Correlation of STAMP2/Akt signaling pathway and macrophage apoptosis was validated by Ad-STAMP2 transfection and STAMP2 siRNA inhibition. The diabetic mice showed typical features of IR, hyperglycaemia. Overexpression of STAMP2 ameliorated IR and decreased serum glucose level. In brachiocephalic lesions, lipid content, macrophage quantity and the vulnerability index were significantly decreased by overexpression of STAMP2. Moreover, the numbers of apoptotic cells and macrophages in lesions were both significantly decreased. In vitro, both mRNA and protein expressions of STAMP2 were increased under high glucose treatment. P-Akt was highly expressed and caspase-3 was decreased after overexpression of STAMP2. However, expression of p-Akt protein was decreased and caspase-3 was increased when STAMP2 was inhibited by siRNA. STAMP2 overexpression could exert a protective effect on diabetic atherosclerosis by reducing IR and diminishing macrophage apoptosis. PMID:24467451

Wang, Jia; Han, Lu; Wang, Zhi-hao; Ding, Wen-yuan; Shang, Yuan-yuan; Tang, Meng-xiong; Li, Wen-bo; Zhang, Yun; Zhang, Wei; Zhong, Ming

2014-01-01

17

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

PubMed

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

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

2014-10-01

18

Anti-inflammatory effects of a Chinese herbal medicine in atherosclerosis via estrogen receptor ? mediating nitric oxide production and NF-?B suppression in endothelial cells  

PubMed Central

Bu-Shen-Ning-Xin Decoction (BSNXD) administration has alleviated the early pathologic damage of atherosclerosis by inhibiting the adhesion molecule expression and upregulating the estrogen receptor (ER) ? expression in endothelial cells, and increasing the serum nitric oxide (NO) level without any effect on serum lipid status, endometrium and fat deposition in liver in ovariectomized rabbits. The BSNXD-derived serum increases ER ? expression in the human umbilical vein endothelial cells (HUVECs), and decreases malondialdehyde (MDA) production, and upregulates eNOS expression then increases NO synthesis through ER?-dependent pathway. NO not only suppresses the LPS-induced NF-?B transcription in HUVECs, but also decreases apoptosis of endothelial cells. The BSNXD-derived serum decreases monocyte chemoattractant protein-1 production, and suppresses cell adhesion molecules (ICAM-1, VCAM-1 and E-selectin) expression in HUVECs injured by oxidized low-density lipoproteins (ox-LDL), and these effects can be abolished by ER? antagonist (R,RTHC) and NO synthase inhibitor (L-NAME). The BSNXD-derived serum-treated HUVECs supernatant reduces CCR2, LFA-1 and VLA-4 expression in monocytes cell line U937 cells, which in turn inhibits adherence of U937 to injured endothelial cells. NO synthesis increases, and MDA production decreases through ER?-mediated pathway that suppresses apoptosis and NF-?B activity in endothelial cells that downregulates adhesion molecules expression on endothelial cells via ER?/NO/NF-?B pathway, and in turn leukocyte adhesion, which suggests BSNXD potential value in prophylaxis atherosclerosis. PMID:23519120

Wang, L; Qiu, X-M; Hao, Q; Li, D-J

2013-01-01

19

Atherosclerosis (image)  

MedlinePLUS

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

20

Stimulation of ?7 nicotinic acetylcholine receptor by AR-R17779 suppresses atherosclerosis and aortic aneurysm formation in apolipoprotein E-deficient mice.  

PubMed

Atherosclerosis is a chronic inflammatory disease. It has been appreciated that vagus nerve inhibits macrophage activation via ?7 nicotinic acetylcholine receptor (nAChR), termed the cholinergic anti-inflammatory pathway. We explored the effects of AR-R17779, a selective ?7nAChR agonist, on atherosclerosis and aneurysm formation in apolipoprotein E (ApoE)-deficient mice. ApoE-deficient mice were fed a high-fat diet (HFD) and angiotensin II (Ang II) was infused by osmotic minipumps from 10-week-old for 4weeks. AR-R17779 was given in drinking water ad libitum. Oil red O staining of the aorta showed that combined loading of HFD and Ang II induced marked atherosclerosis compared with control mice fed a normal chow. Treatment with AR-R17779 significantly reduced atherosclerotic plaque area and improved survival of mice. Treatment with AR-R17779 also suppressed abdominal aortic aneurysm formation. Quantitative RT-PCR of the aorta revealed that mRNA expression levels of interleukin-1?, interleukin-6 and NOX2 were significantly decreased in AR-R17779-treated mice compared with Ang II+HFD mice. AR-R17779 treatment also reduced blood pressure and serum lipid levels. In conclusion, ?7nAChR activation attenuates atherogenesis and aortic abdominal aneurysm formation in ApoE-deficient mice possibly through an anti-inflammatory effect and reduction of blood pressure and lipid levels. Pharmacological activation of ?7nAChR may have a therapeutic potential against atherosclerotic vascular diseases through multiple mechanisms. PMID:24685818

Hashimoto, Toru; Ichiki, Toshihiro; Watanabe, Aya; Hurt-Camejo, Eva; Michaëlsson, Erik; Ikeda, Jiro; Inoue, Eriko; Matsuura, Hirohide; Tokunou, Tomotake; Kitamoto, Shiro; Sunagawa, Kenji

2014-01-01

21

Anagliptin, a DPP-4 inhibitor, suppresses proliferation of vascular smooth muscles and monocyte inflammatory reaction and attenuates atherosclerosis in male apo E-deficient mice.  

PubMed

Dipeptyl peptidase-4 (DPP-4) inhibitors modulate the progression of atherosclerosis. To gain insights into their mechanism of action, 9-wk-old male apolipoprotein E (apoE)-deficient mice were fed a DPP-4 inhibitor, anagliptin-containing diet. The effects of anagliptin were investigated in, a monocyte cell line, human THP-1 cells, and rat smooth muscle cells (SMCs). Treatment with anagliptin for 16 wk significantly reduced accumulation of monocytes and macrophages in the vascular wall, SMC content in plaque areas, and oil red O-stained area around the aortic valve without affecting glucose tolerance or body weight. Serum DPP-4 concentrations were significantly higher in apoE-deficient mice than control mice, and the levels increased with aging, suggesting the involvement of DPP-4 in the progression of atherosclerosis. Indeed, soluble DPP-4 augmented cultured SMC proliferation, and anagliptin suppressed the proliferation by inhibiting ERK phosphorylation. In THP-1 cells, anagliptin reduced lipopolysaccharide-induced TNF-? production with inhibiting ERK phosphorylation and nuclear translocation of nuclear factor-?B. Quantitative analysis also showed that anagliptin reduced the area of atherosclerotic lesion in apoE-deficient mice. These results indicated that the anti-atherosclerotic effect of anagliptin is mediated, at least in part, through its direct inhibition of SMC proliferation and inflammatory reaction of monocytes. PMID:23337530

Ervinna, Nasib; Mita, Tomoya; Yasunari, Eisuke; Azuma, Kosuke; Tanaka, Rica; Fujimura, Satoshi; Sukmawati, Dewi; Nomiyama, Takashi; Kanazawa, Akio; Kawamori, Ryuzo; Fujitani, Yoshio; Watada, Hirotaka

2013-03-01

22

The cost-effectiveness of irbesartan for hypertension.  

PubMed

High blood pressure is a very common problem in the adult and elderly population, both in developed and developing countries. A relatively large number of drug classes are available to treat this condition and prevent its complications, which are not only more frequent in the aforementioned patients but also those affected by metabolic syndrome and/or Type 2 diabetes. Irbesartan is an angiotensin-receptor blocker class drug with good antihypertensive efficacy and specific pharmacological characteristics, whose efficacy has been more deeply evaluated in metabolically complex hypertensive patients. In this review, the authors will analyze its effectiveness in preventing or delaying organ damage in hypertensive patients, with a closer look at the economic implications of treating hypertension with irbesartan in the context of available antihypertensive drugs. PMID:25703678

Borghi, Claudio; Urso, Riccardo; Cicero, Arrigo Fg

2015-04-01

23

Rutaecarpine suppresses atherosclerosis in ApoE-/- mice through upregulating ABCA1 and SR-BI within RCT.  

PubMed

ABCA1 and scavenger receptor class B type I (SR-BI)/CD36 and lysosomal integral membrane protein II analogous 1 (CLA-1) are the key transporter and receptor in reverse cholesterol transport (RCT). Increasing the expression level of ABCA1 and SR-BI/CLA-1 is antiatherogenic. The aim of the study was to find novel antiatherosclerotic agents upregulating expression of ABCA1 and SR-BI/CLA-1 from natural compounds. Using the ABCA1p-LUC and CLA-1p-LUC HepG2 cell lines, we found that rutaecarpine (RUT) triggered promoters of ABCA1 and CLA-1 genes. RUT increased ABCA1 and SR-BI/CLA-1 expression in vitro related to liver X receptor alpha and liver X receptor beta. RUT induced cholesterol efflux in RAW264.7 cells. ApoE-deficient (ApoE(-/-)) mice treated with RUT for 8 weeks showed ?68.43, 70.23, and 85.56% less en face lesions for RUT (L), RUT (M), and RUT (H) groups, respectively, compared with the model group. Mouse macrophage-specific antibody and filipin staining indicated that RUT attenuated macrophages and cholesterol accumulations in atherosclerotic lesions, respectively. Additionally, ABCA1 and SR-BI expression was highly induced by RUT in livers of ApoE(-/-) mice. Meanwhile, RUT treatment significantly increased the fecal (3)H-cholesterol excretion, which demonstrated that RUT could promote RCT in vivo. RUT was identified to be a candidate that protected ApoE(-/-) mice from developing atherosclerosis through preferentially promoting activities of ABCA1 and SR-BI within RCT. PMID:24908654

Xu, Yanni; Liu, Qi; Xu, Yang; Liu, Chang; Wang, Xiao; He, Xiaobo; Zhu, Ningyu; Liu, Jikai; Wu, Yexiang; Li, Yongzhen; Li, Ni; Feng, Tingting; Lai, Fangfang; Zhang, Murui; Hong, Bin; Jiang, Jian-Dong; Si, Shuyi

2014-06-01

24

What Causes Atherosclerosis?  

MedlinePLUS

... page from the NHLBI on Twitter. What Causes Atherosclerosis? The exact cause of atherosclerosis isn't known. ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 10/14/2014 August 4, 2014 Atherosclerosis Clinical ...

25

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

SciTech Connect

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

Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)] [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)] [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

2011-03-04

26

Experimental atherosclerosis  

Microsoft Academic Search

Almost one-hundred years ago the first evidence of experimental atherosclerosis was reported. Over the past century, significant advances have been made in the development of animal models of human coronary artery disease. In this minireview, induction of atherosclerotic lesions in several animal models including rodents (mice, rabbits, rats, hamsters, guinea pigs), avian (pigeons, chickens, quail), swine, carnivora (dogs, cats), and

Mohammed H. Moghadasian

2002-01-01

27

Increased Expression of Chitinase 3-Like 1 in Aorta of Patients with Atherosclerosis and Suppression of Atherosclerosis in Apolipoprotein E-Knockout Mice by Chitinase 3-Like 1 Gene Silencing  

PubMed Central

Introduction. The purpose of this study was to investigate the changes of chitinase 3-like 1 (CHI3L1) in the aorta of patients with coronary atherosclerosis and to determine whether inhibition of CHI3L1 by lentivirus-mediated RNA interference could stabilize atherosclerotic plaques in apolipoprotein E-knockout (ApoE?/?) mice. Methods. We collected discarded aortic specimens from patients undergoing coronary artery bypass graft surgery and renal arterial tissues from kidney donors. A lentivirus carrying small interfering RNA targeting the expression of CHI3L1 was constructed. Fifty ApoE?/? mice were divided into control group and CHI3L1 gene silenced group. A constrictive collar was placed around carotid artery to induce plaques formation. Then lentivirus was transfected into carotid plaques. Results. We found that CHI3L1 was overexpressed in aorta of patients with atherosclerosis and its expression was correlated with the atherosclerotic risk factors. After lentivirus transduction, mRNA and protein expression of CHI3L1 were attenuated in carotid plaques, leading to reduced plaque content of lipids and macrophages, and increased plaque content of collagen and smooth muscle cells. Moreover, CHI3L1 gene silencing downregulated the expression of local proinflammatory mediators. Conclusions. CHI3L1 is overexpressed in aorta from patients with atherosclerosis and the lentivirus-mediated CHI3L1 gene silencing could represent a new strategy to inhibit plaques progression. PMID:24729664

Gong, Zushun; Xing, Shanshan; Zheng, Fei; Xing, Qichong

2014-01-01

28

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

Federal Register 2010, 2011, 2012, 2013, 2014

...irbesartan), oral tablets, 25 mg/300 mg, were withdrawn from sale for reasons of safety or effectiveness. In addition, Lupin Pharmaceuticals, Inc. submitted a citizen petition dated November 10, 2011 (Docket No. FDA-2011-P-0822),...

2012-01-11

29

Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke  

PubMed Central

Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs. PMID:24065095

Kikuchi, Kiyoshi; Tancharoen, Salunya; Ito, Takashi; Morimoto-Yamashita, Yoko; Miura, Naoki; Kawahara, Ko-ichi; Maruyama, Ikuro; Murai, Yoshinaka; Tanaka, Eiichiro

2013-01-01

30

Living with Atherosclerosis  

MedlinePLUS

... page from the NHLBI on Twitter. Living With Atherosclerosis Improved treatments have reduced the number of deaths ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 10/14/2014 August 4, 2014 Atherosclerosis Clinical ...

31

Naringenin and atherosclerosis: a review of literature.  

PubMed

Atherosclerosis is a multifactorial disease mainly caused by deposition of low-density lipoprotein (LD) cholesterol in macrophages of arterial walls. Atherosclerosis leads to heart attacks as well as stroke. Epidemiological studies showed that there is an inverse correlation between fruit and vegetable consumption and the risk of atherosclerosis. The promising effect of high vegetable and fruit containing diet on atherosclerosis is approved by several experimental studies on isolated phytochemicals such as flavonoids. Flavonoids are known to up-regulate endogenous antioxidant system, suppress oxidative and nitrosative stress, decrease macrophage oxidative stress through cellular oxygenase inhibition as well as interaction with several signal transduction pathways and from these ways, have therapeutic effects against atherosclerosis. Naringenin is a well known flavonoid belonging to the chemical class of flavanones. It is especially abundant in citrus fruits, especially grapefruits. A plethora of evidences ascribes to naringenin antiatherosclerotic effects. Naringenin abilities to decrease LDL and triglycerides as well as inhibit glucose uptake; increase high-density lipoprotein (HDL); co-oxidation of NADH; suppress protein oxidation; protect against intercellular adhesion molecule-1(ICAM-1); suppress macrophage inflammation; inhibit leukotriene B4, monocyte adhesion and foam cell formation; induce of HO-1 and G 0/G 1 cell cycle arrest in vascular smooth muscle cells (VSMC) and down regulate atherosclerosis related genes are believed to have crucial role in the promising role against atherosclerosis. In the present review, we have summarized the available literature data on the anti-atherosclerotic effects of naringenin and its possible mechanisms of action. PMID:25483717

Orhan, Ilkay E; Nabavi, Seyed F; Daglia, Maria; Tenore, Gian C; Mansouri, Kowsar; Nabavi, Seyed M

2015-01-01

32

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

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

Neutel, Joel M

2011-07-01

33

Simultaneous determination of the acid\\/base antihypertensive drugs celiprolol, bisoprolol and irbesartan in human plasma by liquid chromatography  

Microsoft Academic Search

A simple, rapid method for the simultaneous determination of cardiovascular drugs: celiprolol, bisoprolol and irbesartan in human plasma is described. The two main features of the proposed method deal first, with a simultaneous solid phase extraction of weakly basic beta-blockers derivatives and irbesartan which exhibit weak acidic properties; second with an absorbance monitoring using diode array detection in order to

E Caudron; S Laurent; E. M Billaud; P Prognon

2004-01-01

34

HIV and Atherosclerosis  

MedlinePLUS

HIV and Atherosclerosis Updated:Jan 22,2014 Featured Video How is HIV Related to Atherosclerosis? Length: 2: ... improve your cholesterol ratios, with or without HIV. HIV and Your Heart • Home • About HIV • HIV and ...

35

Decay-accelerating factor suppresses complement C3 activation and retards atherosclerosis in low-density lipoprotein receptor-deficient mice.  

PubMed

Decay-accelerating factor (DAF; CD55) is a membrane protein that regulates complement pathway activity at the level of C3. To test the hypothesis that DAF plays an essential role in limiting complement activation in the arterial wall and protecting from atherosclerosis, we crossed DAF gene targeted mice (daf-1(-/-)) with low-density lipoprotein-receptor deficient mice (Ldlr(-/-)). Daf-1(-/-)Ldlr(-/-) mice had more extensive en face Sudan IV staining of the thoracoabdominal aorta than Ldlr(-/-) mice, both following a 12-week period of low-fat diet or a high-fat diet. Aortic root lesions in daf-1(-/-)Ldlr(-/-) mice on a low-fat diet showed increased size and complexity. DAF deficiency increased deposition of C3d and C5b-9, indicating the importance of DAF for downstream complement regulation in the arterial wall. The acceleration of lesion development in the absence of DAF provides confirmation of the proinflammatory and proatherosclerotic potential of complement activation in the Ldlr(-/-) mouse model. Because upstream complement activation is potentially protective, this study underlines the importance of DAF in shielding the arterial wall from the atherogenic effects of complement. PMID:19729477

Leung, Viola W Y; Yun, Sheng; Botto, Marina; Mason, Justin C; Malik, Talat H; Song, Wenchao; Paixao-Cavalcante, Danielle; Pickering, Matthew C; Boyle, Joseph J; Haskard, Dorian O

2009-10-01

36

High-performance liquid chromatographic assay for the quantitation of irbesartan (SR 47436\\/BMS-186295) in human plasma and urine  

Microsoft Academic Search

A selective, accurate, precise and reproducible high-performance liquid chromatographic assay was developed for the quantitation of irbesartan, an angiotensin II antagonist, in human plasma and urine samples. The method involved solid-phase extraction of irbesartan and internal standard (I.S.) using a 100-mg Isolute CN cartridge. A portion of the eluate was injected onto an ODS analytical column connected to a fluorescence

Shu-Ying Chang; Daisy B Whigan; Nimish N Vachharajani; Rajesh Patel

1997-01-01

37

Vinpocetine attenuates lipid accumulation and atherosclerosis formation  

SciTech Connect

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

Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)] [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States)] [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)] [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)

2013-05-10

38

Depression and atherosclerosis.  

PubMed

The aim of this paper was to examine the interaction between depression and atherosclerosis through a systematic review. A Medline search was performed from 1966 through 2009 using relevant terms such as depression, epidemiology and atherosclerosis. This was supplemented by a thorough manual search using bibliographies of reviews and full articles. The papers were divided and analyzed separately for each vascular bed. Depression is diagnosed usually before atherosclerosis becomes obvious. The contribution of depression in the development of atherosclerosis emerges from various mechanisms, including lack of physical activity, that exist in this illness. Controversies about the etiology and pathogenesis exist. These interactions of all elements and the importance of each one have not been investigated adequately. Repeated objective measurements for atherosclerosis are lacking. There is an association between depression and atherosclerosis, but the strength of this relationship has to be determined. Prospective studies are needed to determine the early and long term effects of their interaction. PMID:21427645

Saleptsis, V G; Labropoulos, N; Halaris, A; Angelopoulos, N V; Giannoukas, A D

2011-04-01

39

Dendritic cells in atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory disease with activation of both the innate and adaptive arms of the immune system. Dendritic cells (DCs) are potent activators of adaptive immunity and have been identified in the normal arterial wall and within atherosclerotic lesions. Recent evidence points to a functional role for DCs in all stages of atherosclerosis because of their myriad functions including lipid uptake, antigen presentation, efferocytosis, and inflammation resolution. Moreover, DC-based vaccination strategies are currently being developed for the treatment of atherosclerosis. This review will focus on the current evidence as well as the proposed roles for DCs in the pathogenesis of atherosclerosis and discuss future therapeutic strategies. PMID:24196454

Tabas, Ira

2013-01-01

40

Dietary cholesterol and atherosclerosis  

Microsoft Academic Search

The perceived relationship between dietary cholesterol, plasma cholesterol and atherosclerosis is based on three lines of evidence: animal feeding studies, epidemiological surveys, and clinical trials. Over the past quarter century studies investigating the relationship between dietary cholesterol and atherosclerosis have raised questions regarding the contribution of dietary cholesterol to heart disease risk and the validity of dietary cholesterol restrictions based

Donald J. McNamara

2000-01-01

41

Vaccine for atherosclerosis.  

PubMed

Atherosclerosis is an immune-mediated inflammatory disease of the arterial wall, with both the innate and adaptive immune systems responding to many endogenous and exogenous antigens. Both proatherogenic as well as atheroprotective roles have been identified for the immune system in atherosclerosis. Hence, it is conceivable that an immunomodulatory strategy via active immunization against many of these antigens could potentially alter the natural history of atherosclerosis. This review discusses: 1) the complex role of important components of the innate and adaptive immune systems in atherogenesis; 2) the nature of many antigens that have been tested successfully in vaccine formulations to reduce atherosclerosis in pre-clinical experimental models; and 3) the potential opportunities and challenges for clinical application of vaccination for atherosclerosis in the future. PMID:25541132

Shah, Prediman K; Chyu, Kuang-Yuh; Dimayuga, Paul C; Nilsson, Jan

2014-12-30

42

Animal models of atherosclerosis  

PubMed Central

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

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

2014-01-01

43

Atherosclerosis and Stroke  

MedlinePLUS

... reached their 50s or 60s. View a detailed animation of atherosclerosis . Males and people with a family ... and Live Our Interactive Cardiovascular Library has detailed animations and illustrations to help you learn about conditions, ...

44

The Mechanics of Atherosclerosis  

NSDL National Science Digital Library

In this module, developed as part of Cornell's Learning Initiative in Medicine and Bioengineering (CLIMB), students will understand how arterial stiffness contributes to disturbed blood flow and the progression of atherosclerosis. This is done using polymer chemistry, fabricating gels of varying stiffness, and designing experiments to quantify gel stiffness. This module contains a teacher's guide, powerpoint instructional lecture "Atherosclerosis", instructional student activity sheets for laboratory activities, and multiple choice quizzes. CLIMB is part of the NSF GK-12 program.

CLIMB: Cornell's Learning Initiative in Medicine and Bioengineering

45

Chitinase Inhibition Promotes Atherosclerosis in Hyperlipidemic Mice  

PubMed Central

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

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

2014-01-01

46

Thrombin generation and atherosclerosis.  

PubMed

Atherosclerosis is a major cause of mortality worldwide. The important role inflammation plays in atherosclerosis is evident through the participation of inflammatory cells in the development and progression of the disease. Thrombin is the central protease of the coagulation cascade, involved in the formation of a hemostatic plug to avoid severe bleeding. In addition, thrombin is a key factor in regulating inflammatory processes, signaling through protease activated receptors. We propose that thrombin may be a relevant factor in the atherosclerosis coagulation-inflammation axis. Human histological data show abundant coagulation activity within atherosclerotic lesions with thrombin activity being related to atherosclerotic plaque development and (in)stability. Animal studies establish that the generated thrombin level relates to progression of atherosclerosis, with hypercoagulability producing advanced atherosclerosis in mice with an Apolipoprotein E-deficient (ApoE(-/-)) background. Several studies show that administration of direct oral anticoagulants, like dabigatran and rivaroxaban, attenuate atherosclerosis development in ApoE(-/-) mice. In this review we explore several mechanisms by which thrombin may operate in modifying the chronic process of atherosclerosis. One of the key elements may be the conversion of thrombin, from a physiological regulator of hemostasis towards an inflammation-mediator under pathophysiological conditions, contributing to a switch in the thrombin-activated protein C (APC) regulation. The ongoing inflammatory activity, indicated by the activation of pro-inflammatory cytokines, neutrophils and neutrophil extracellular traps, drive thrombin generation, while diminishing APC formation. The net result is accelerated pro-inflammatory and pro-thrombotic changes in blood and in the vessel wall. We conclude that these atherogenic influences of thrombin may be clinically relevant in the long-term. Further the treatment with long-term anticoagulant therapy deserves further attention as to its potential, vascular side effects. PMID:24241912

Kalz, Jana; ten Cate, Hugo; Spronk, Henri M H

2014-01-01

47

Mitochondrial DNA damage and atherosclerosis  

E-print Network

evidence that mitochondrial DNA (mtDNA) damage leads to mitochondrial dysfunction and promotes atherosclerosis directly. In this review we discuss the recent evidence for and mechanisms linking mtDNA defects and atherosclerosis, and suggest areas...

Yu, E. PK.; Bennett, M. R.

2014-01-01

48

Effects of garlic on atherosclerosis  

Microsoft Academic Search

This review discusses the use of garlic and garlic preparations as agents for prevention and treatment of atherosclerosis and atherosclerosis-related diseases. Garlic indirectly effects atherosclerosis by reduction of hyperlipidemia, hypertension, and probably diabetes mellitus and prevents thrombus formation. In addition, in animal models, garlic causes direct antiatherogenic (preventive) and antiatherosclerotic (causing regression) effects at the level of artery wall. Garlic's

Alexander N. Orekhov; Jörg Grünwald

1997-01-01

49

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

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

Xiaojun Ren; Guangju Guan; Gang Liu; Gaohong Liu

2009-01-01

50

Soy, Isoflavones and Atherosclerosis  

Microsoft Academic Search

Consumption of soy protein is associated with a lower risk of cardiovascular disease in man, and reduced atherosclerosis in a variety of experimental animals. Although a portion of the cardiovascular protective effects appears to be due to reductions in plasma lipoprotein concentration, in most people the magnitude of this effect is relatively small. In many, but not all studies using

R. Clair; M. Anthony

51

Intercellular Communication in Atherosclerosis  

NSDL National Science Digital Library

Cell-to-cell communication is a process necessary for physiological tissue homeostasis and appears often altered during disease. Gap junction channels, formed by connexins, allow the direct intercellular communication between adjacent cells. After a brief review of the pathophysiology of atherosclerosis, we will discuss the role of connexins throughout the different stages of the disease.

Laurent Burnier (University of Lausanne)

2009-02-01

52

Treating atherosclerosis with regulatory T cells.  

PubMed

Regulatory T cells (Tregs) play an important role in the regulation of T-cell-mediated immune responses through suppression of T-cell proliferation and secretion of inhibitory cytokines, such as interleukin-10 and transforming growth factor-?. Impaired Treg numbers and function have been associated with numerous diseases, and an imbalance between proinflammatory/proatherogenic cells and Tregs promotes atherosclerotic disease. Restoration of this balance by inducing Tregs has great therapeutic potential to prevent cardiovascular disease. In addition to suppressing differentiation and function of effector T cells, Tregs have been shown to induce anti-inflammatory macrophages, inhibit foam cell formation and to influence cholesterol metabolism. Furthermore, Tregs suppress immune responses of endothelial cells and innate lymphoid cells. In this review, we focus on the recent knowledge on Treg subsets, their activity and function in atherosclerosis, and discuss promising strategies to use Tregs as a therapeutic tool to prevent cardiovascular disease. PMID:25414253

Foks, Amanda C; Lichtman, Andrew H; Kuiper, Johan

2015-02-01

53

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

SciTech Connect

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

Cheng, Tain-Junn [Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Department of Neurology, Chi Mei Medical Center, 901 Chung-Hwa Road, Tainan 710, Taiwan (China); Department of Occupational Medicine, Chi Mei Medical Center, 901 Chung-Hwa Road, Yongkang, Tainan 710, Taiwan (China); Department of Occupational Safety, College of Environment, Chia Nan University of Pharmacy and Science, 60, Sec. 1, Erh-Jen Road, Jen-Te, Tainan 711, Taiwan (China); Chuu, Jiunn-Jye [Department of Biotechnology, Southern Taiwan University, 1 Nan-Tai Street, Yongkang, Tainan 710, Taiwan (China); Chang, Chia-Yu [Department of Neurology, Chi Mei Medical Center, 901 Chung-Hwa Road, Tainan 710, Taiwan (China); Department of Biotechnology, Southern Taiwan University, 1 Nan-Tai Street, Yongkang, Tainan 710, Taiwan (China); Tsai, Wan-Chen; Chen, Kuan-Jung [Department of Biotechnology, Southern Taiwan University, 1 Nan-Tai Street, Yongkang, Tainan 710, Taiwan (China); Guo, How-Ran, E-mail: hrguo@mail.ncku.edu.tw [Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Sustainable Environment Research Center, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Center for Occupational and Environmental Health and Preventive Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China)

2011-10-15

54

Chapter 7. Atherosclerosis and hypertension  

PubMed Central

Autopsy studies of atherosclerosis of the aorta and the coronary arteries were carried out in 3134 subjects with essential hypertension. A comparison was made with low, average, and high atherosclerosis groups. Essential hypertension was found to accelerate the development of all types of aortic lesion, except fatty streak, as compared with the standardized average atherosclerosis group, and to accelerate the development of fibrous plaque but not complicated and calcified lesions as compared with the high atherosclerosis group. The extent of fibrous plaque in the coronary arteries was greater in the essential hypertension group than in the low and standardized average atherosclerosis groups but did not differ from that in the high atherosclerosis group. The extent of complicated and calcified lesions and the prevalence of coronary stenosis were higher in the high atherosclerosis group than in cases of hypertension. Geographical differences in atherosclerosis among hypertensives in different towns reflected the findings for the whole material. Symptomatic hypertension was found to accelerate aortic atherosclerosis at least to the same extent as essential hypertension. It was conductive to coronary atherosclerosis but not to the same extent as essential hypertension. Coronary stenosis and various manifestations of coronary heart disease were rare in symptomatic hypertension. PMID:1087193

Matova, E. E.; Vihert, A. M.

1976-01-01

55

Danger signaling in atherosclerosis.  

PubMed

All aspects of the pathogenesis of atherosclerosis are critically influenced by the inflammatory response in vascular plaques. Research in the field of innate immunity from the past 2 decades has uncovered many novel mechanisms elucidating how immune cells sense microbes, tissue damage, and metabolic derangements. Here, we summarize which triggers of innate immunity appear during atherogenesis and by which pathways they can contribute to inflammation in atherosclerotic plaques. The increased understanding gained from studies assessing how immune activation is associated with the pathogenesis of atherosclerosis has provided many novel targets for potential therapeutic intervention. Excitingly, the concept that inflammation may be the core of cardiovascular disease is currently being clinically evaluated and will probably encourage further studies in this area. PMID:25593277

Zimmer, Sebastian; Grebe, Alena; Latz, Eicke

2015-01-16

56

Insulin Resistance and Atherosclerosis  

PubMed Central

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

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

2008-01-01

57

Animal models of atherosclerosis.  

PubMed

Cardiovascular disease is currently the predominant cause of mortality worldwide and its incidence is expected to increase significantly during the next decades owing to the unhealthy effects of modern lifestyle habits (e.g., obesity and lack of physical exercise). Cardiovascular death is frequently associated with acute myocardial infarction or stroke, which are generally the ultimate consequence of an underlying atherosclerotic process. Small and big animal models are valuable tools to understand the molecular mechanisms underlying atherosclerotic plaque formation and progression, as well as the occurrence of associated ischemic events. Moreover, animal models of atherosclerosis are pivotal for testing mechanistic hypothesis and for translational research, including the assessment of dietary and/or pharmacological interventions and the development of imaging technologies and interventional devices. In this chapter, we will describe the most widely used animal models that have permitted major advances in atherosclerosis research and significant improvements in the treatment and diagnosis of atherosclerotic disease. PMID:22137427

Fuster, José J; Castillo, Ana I; Zaragoza, Carlos; Ibáñez, Borja; Andrés, Vicente

2012-01-01

58

Glycosyltransferases, glycosylation and atherosclerosis.  

PubMed

Cardiovascular diseases arising from atherosclerosis are currently the leading cause of mortality worldwide. Leukocyte recruitment is a key step for the successful initiation of atherosclerosis and occurs predominantly in the inflamed endothelium. Leukocyte recruitment is mediated by a group of adhesive molecules and chemokine receptors, which are often glycosylated protein. Recent studies demonstrated that post-translational glycosylation by glycosyltransferases is necessary for adhesive molecules and chemokine receptors activities. Several glycosyltransferases, such as ?2,3-sialyltransferases IV, ?1,3-fucosyltransferases IV and VII, core 2 ?1,6-N-acetylglucosaminyltransferase-I, are considered to participate in the synthesis of glycosylation for adhesive molecules and chemokine receptors, and the initiation of atherosclerotic lesions. In this review, we will discuss new data concerning the roles of different glycosyltransferases in atherogenesis. The knowledge of glycosyltransferases in atherogenesis offers the opportunity to develop novel therapeutic strategies. PMID:25294497

Pu, Qianghong; Yu, Chao

2014-12-01

59

Inflammation and atherosclerosis  

Microsoft Academic Search

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

Mehdi H. Shishehbor; Deepak L. Bhatt

2004-01-01

60

Atherosclerosis and osteoporosis.  

PubMed

Atherosclerosis and osteoporosis are degenerative chronic diseases with a high incidence in developed countries. They are silent processes with a great economic cost that becomes evident when complications become overt. Numerous epidemiological studies show an independent association between the two diseases that is not related to age or other cardiovascular risk factors. This review analyzes the clinical studies that support this association and describes the possible common etiopathogenic and physiopathological mechanisms. PMID:18299695

Pérez Castrillón, J L; de Luis, D; Duenas-Laita, A

2008-02-01

61

Hyperlipidemia, atherosclerosis, and diabetes.  

PubMed

At present the two different mechanisms underlying the hypertriglyceridemia of diabetes are reasonably well defined. The rationale of therapy has grown from this knowledge. One form of hyperlipidemia is due to the hyperinsulinemia which results from the patient's resistance to insulin. The approach to treatment aims to overcome the insulin resistance. In most patients this is done by treating their obesity. The other form of hypertriglyceridemia results from insulin deficiency and is treated by bringing the patient's diabetes under control. There is strongly suggestive evidence that hypertriglyceridemia may be associated with a high risk of atherosclerosis. The reason for treating hypertriglyceridemia in general, and in the diabetic in particular, is to reduce this risk. However, it must be conceded that, at the moment, there is no information about the effect of lower triglyceride levels on the incidence of atherosclerosis. Hence much epidemiologic research is needed before our rationale for treatment can move from the realm of hope to the realm of definite proof. In the mean time an attack on this and the other risk factors is the best way we have to attempt to prevent the major complication of diabetes, atherosclerosis. PMID:206921

Steiner, G

1978-03-01

62

Inflammation, atherosclerosis, and psoriasis.  

PubMed

Increasing evidence supports an important role for inflammation in all phases of atherosclerosis, from initiation of the fatty streak to final culmination in acute coronary syndromes. Numerous inflammatory biomarkers including cell adhesion molecules, cytokines, chemokines, and acute-phase reactants such as fibrinogen, serum amyloid A, and C-reactive protein (CRP) have been shown to predict cardiovascular (CVD) events. Several prospective studies have shown a consistent and robust relationship between levels of high-sensitivity CRP and the risk of future CVD events. Toll-like receptors are pattern recognition receptors and members of the innate immune system that contribute to inflammation and appear to play key roles in atherosclerosis. Lipoprotein-associated phospholipase A2 may also be an independent CVD risk factor. Psoriasis has been associated with an increasing risk for atherosclerosis, including coronary artery disease and stroke. Patients with psoriasis have a 5-year shorter life expectancy, most frequently due to CVD. Psoriasis is associated with a chronic inflammatory state and with elevated levels of CRP and other inflammatory cytokines and these may play a causative role in the increased risk of psoriatic patients for CVD. Patients with psoriasis may represent an emerging risk population and patients with moderate to severe psoriasis should be screened and aggressively treated for CVD risk factors. PMID:22359071

Siegel, David; Devaraj, Sridevi; Mitra, Anupam; Raychaudhuri, Siba P; Raychaudhuri, Smriti K; Jialal, Ishwarlal

2013-04-01

63

Simultaneous determination of the acid/base antihypertensive drugs celiprolol, bisoprolol and irbesartan in human plasma by liquid chromatography.  

PubMed

A simple, rapid method for the simultaneous determination of cardiovascular drugs: celiprolol, bisoprolol and irbesartan in human plasma is described. The two main features of the proposed method deal first, with a simultaneous solid phase extraction of weakly basic beta-blockers derivatives and irbesartan which exhibit weak acidic properties; second with an absorbance monitoring using diode array detection in order to insure an improved selectivity. The separation is performed on a C(18) Kromasil 4.6 mm x 150 mm column using a linear gradient to achieve an entire separation of the four species in less than 20 min. The full analytical validation is performed according to guidance for industry for bioanalytical method validation. Linearity of the response was demonstrated for each drug for a range fulfilling the reported plasma levels, that is 10-500, 5-250 and 20-1000 ng l(-1) for celiprolol, bisoprolol and irbesartan respectively. Intra- and inter-day relative standard deviations for all compounds were, in any case, lower than 11% and the method exhibits a convenient accuracy (percentage of relative error lower than 6% for each drug). In each case, the LOD were sufficient to detect post dose trough concentrations for checking patient's observance. Moreover, selectivity towards either endogenous species or co-administered drugs was demonstrated by combination of the use of the solid phase extraction process, gradient elution and diode array detection facilities, making thus, the proposed technique especially suitable for routine drug monitoring of resistant hypertensive patients. PMID:14751804

Caudron, E; Laurent, S; Billaud, E M; Prognon, P

2004-03-01

64

High-performance liquid chromatographic assay for the quantitation of irbesartan (SR 47436/BMS-186295) in human plasma and urine.  

PubMed

A selective, accurate, precise and reproducible high-performance liquid chromatographic assay was developed for the quantitation of irbesartan, an angiotensin II antagonist, in human plasma and urine samples. The method involved solid-phase extraction of irbesartan and internal standard (I.S.) using a 100-mg Isolute CN cartridge. A portion of the eluate was injected onto an ODS analytical column connected to a fluorescence detector that was set at an excitation wavelength of 250 nm and an emission wavelength of 371 nm. The mobile phase consisted of 50% acetonitrile and a 50% weak phosphate-triethylamine solution, pH 3.5, at a flow-rate of 0.8 ml/min. The assay was linear from 1 to 1000 ng/ml with both plasma and urine. In either matrix, the lower limit of quantitation was 1 ng/ml. The analyses of quality control samples indicated that the nominal values could be predicted with an accuracy >95%. The inter- and intra-day coefficients of variation for the analyses in both matrices were <8%. Irbesartan was stable in both human plasma and urine for at least seven months at -20 degrees C. The application of the assay to a pharmacokinetic study is described. PMID:9449566

Chang, S Y; Whigan, D B; Vachharajani, N N; Patel, R

1997-11-21

65

Endothelial progenitor cells in atherosclerosis  

PubMed Central

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

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

2012-01-01

66

How Can Atherosclerosis Be Prevented or Delayed?  

MedlinePLUS

... page from the NHLBI on Twitter. How Can Atherosclerosis Be Prevented or Delayed? Taking action to control ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 10/14/2014 August 4, 2014 Atherosclerosis Clinical ...

67

Monocyte fate in atherosclerosis.  

PubMed

Monocytes and their descendant macrophages are essential to the development and exacerbation of atherosclerosis, a lipid-driven inflammatory disease. Lipid-laden macrophages, known as foam cells, reside in early lesions and advanced atheromata. Our understanding of how monocytes accumulate in the growing lesion, differentiate, ingest lipids, and contribute to disease has advanced substantially over the last several years. These cells' remarkable phenotypic and functional complexity is a therapeutic opportunity: in the future, treatment and prevention of cardiovascular disease and its complications may involve specific targeting of atherogenic monocytes/macrophages and their products. PMID:25538208

Hilgendorf, Ingo; Swirski, Filip K; Robbins, Clinton S

2015-02-01

68

B Cell Subsets in Atherosclerosis  

PubMed Central

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

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

2012-01-01

69

The immune system in atherosclerosis  

Microsoft Academic Search

Cardiovascular disease, a leading cause of mortality worldwide, is caused mainly by atherosclerosis, a chronic inflammatory disease of blood vessels. Lesions of atherosclerosis contain macrophages, T cells and other cells of the immune response, together with cholesterol that infiltrates from the blood. Targeted deletion of genes encoding costimulatory factors and proinflammatory cytokines results in less disease in mouse models, whereas

Andreas Hermansson; Göran K Hansson

2011-01-01

70

LRP: role in vascular wall integrity and protection from atherosclerosis.  

PubMed

Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of atherosclerosis. The low-density lipoprotein receptor-related protein (LRP1) mediates suppression of SMC migration induced by platelet-derived growth factor (PDGF). Here we show that LRP1 forms a complex with the PDGF receptor (PDGFR). Inactivation of LRP1 in vascular SMCs of mice causes PDGFR overexpression and abnormal activation of PDGFR signaling, resulting in disruption of the elastic layer, SMC proliferation, aneurysm formation, and marked susceptibility to cholesterol-induced atherosclerosis. The development of these abnormalities was reduced by treatment with Gleevec, an inhibitor of PDGF signaling. Thus, LRP1 has a pivotal role in protecting vascular wall integrity and preventing atherosclerosis by controlling PDGFR activation. PMID:12690199

Boucher, Philippe; Gotthardt, Michael; Li, Wei-Ping; Anderson, Richard G W; Herz, Joachim

2003-04-11

71

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

PubMed Central

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

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

2011-01-01

72

Helicobacter pylori Seropositivity and Atherosclerosis Risk Factors  

Microsoft Academic Search

Certain viral and bacterial infections may contribute to the initiation and progression of atherosclerosis. The aim of this study is to determine whether Helicobacter pylori (HP) seropositivity contributes to conventional atherosclerosis risk factors in the development of an early sign of atherosclerosis: intima-media thickness (IMT) of the carotid artery. Eighty-four patients who had at least two conventional atherosclerosis risk factors

Yakup Ekmekçi; Yasemin Karadeniz; Seyfettin Köklü; Teoman Apan; Mesut Sezikli; Tolga Demirel

2004-01-01

73

Macrophage function in atherosclerosis  

PubMed Central

Cation channels of the Transient Receptor Potential Canonical (TRPC) group, which belong to the larger TRP superfamily of channel proteins, are critical players in cardiovascular disease. Recent studies underscored a role of TRPC3 in macrophage survival and efferocytosis, two critical events in atherosclerosis lesion development. Also, other members of the TRP channel superfamily are found expressed in monocytes/macrophages, where they participate in processes that might be of significance to atherogenesis. These observations set a framework for future studies aimed at defining the ultimate functions not only of TRPC3, but probably other TRP channels, in macrophage biology. The purpose of this manuscript is to provide a timely revision of existing evidence on the role of members of the TRP channel superfamily, in particular TRPCs, in macrophages and discuss it in the context of the macrophage’s function in atherogenesis. PMID:22909953

Tano, Jean-Yves K.; Lee, Robert H.; Vazquez, Guillermo

2012-01-01

74

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

SciTech Connect

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

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

2014-01-17

75

Dietary flax seed in prevention of hypercholesterolemic atherosclerosis  

Microsoft Academic Search

Oxygen free radicals (OFRs) have been implicated in the development of hypercholesterolemic atherosclerosis. Flax seed is the richest source of ?-3 fatty acid and lignans. ?-3 Fatty acid suppresses the production of interleukin-1 (IL-1), tumor necrosis factor (TNF) and leukotriene B4 (LTB4), and of OFRs by polymorphonuclear leukocytes (PMNLs) and monocytes. Lignans possess anti-platelet activating factor (PAF) activity and are

Kailash Prasad

1997-01-01

76

Cardiac repolarization and its relation to ventricular geometry and rate in reverse remodelling during antihypertensive therapy with irbesartan or atenolol: results from the SILVHIA study  

Microsoft Academic Search

Hypertensive left ventricular (LV) hypertrophy is associated with a substantial risk for malignant arrhythmias and sudden death. According to recent results, antihypertensive therapy with the angiotensin II type 1 receptor blocker irbesartan reverses both structural and electrical remodelling. However, the relation between the LV geometric pattern (concentric vs eccentric) and electrical reverse remodelling has not been characterized, neither has the

K Malmqvist; T Kahan; M Edner; L Bergfeldt

2007-01-01

77

Chapter 10. Atherosclerosis and rheumatic heart disease  

PubMed Central

The extent of aortic atherosclerosis in subjects with rheumatic heart diseases was similar to that in the standardized average atherosclerosis group of subjects. The extent of coronary atherosclerosis, particularly in men, was similar to that in the low atherosclerosis group. In the aorta, this finding was accounted for by the greater extent of complicated and raised lesions; in the coronary arteries, it was accounted for by the lesser extent of fibrous plaque. Coronary stenosis, fresh myocardial infarction, and large myocardial scar occurred much less frequently in rheumatic subjects than in the high atherosclerosis group. There was no difference in the frequency of stenosis between the rheumatic and low atherosclerosis groups. PMID:1087196

Ždanov, V. S.

1976-01-01

78

Renal protection by low dose irbesartan in diabetic nephropathy is paralleled by a reduction of inflammation, not of endoplasmic reticulum stress.  

PubMed

Diabetes can disrupt endoplasmic reticulum (ER) homeostasis which leads to ER stress. ER stress-induced renal apoptosis seems to be involved in the development of diabetic nephropathy. The present study was designed to investigate the contribution of reduced ER stress to the beneficial effects of an angiotensin receptor blocker. Insulin-dependent diabetes mellitus was induced by streptozotocin injections to hypertensive mRen2-transgenic rats. After 2weeks animals were treated with 0.7mg/kg/day irbesartan. Blood glucose, blood pressure and protein excretion were assessed. Expression of ER stress markers was measured by real-time PCR. Immunohistochemistry was performed to detect markers of ER stress, renal damage and infiltrating cells. Glomerulosclerosis and apoptosis were evaluated. Diabetic mRen2-transgenic rats developed renal injury with proteinuria, tubulointerstitial cell proliferation as well as glomerulosclerosis and podocyte injury. Moreover, an increase in inflammation, podocyte ER stress and apoptosis was detected. Irbesartan somewhat lowered blood pressure and reduced proteinuria, tubulointerstitial cell proliferation and glomerulosclerosis. Podocyte damage was ameliorated but markers of ER stress (calnexin, grp78) and apoptosis were not reduced by irbesartan. On the other hand, inflammatory cell infiltration in the tubulointerstitium and the glomerulus was significantly attenuated. We conclude that irbesartan reduced renal damage even in a very low dose. The beneficial effects of low dose irbesartan were paralleled by a reduction of blood pressure and inflammation but not by a reduction of ER stress and apoptosis. Thus, sustained endoplasmic reticulum stress in the kidney does not necessarily lead to increased inflammation and tubulointerstitial or glomerular injury. PMID:24418215

Hartner, Andrea; Cordasic, Nada; Klanke, Bernd; Menendez-Castro, Carlos; Veelken, Roland; Schmieder, Roland E; Hilgers, Karl F

2014-04-01

79

What Are the Signs and Symptoms of Atherosclerosis?  

MedlinePLUS

... Twitter. What Are the Signs and Symptoms of Atherosclerosis? Atherosclerosis usually doesn't cause signs and symptoms ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 10/14/2014 August 4, 2014 Atherosclerosis Clinical ...

80

Who Is at Risk for Atherosclerosis?  

MedlinePLUS

... from the NHLBI on Twitter. Who Is at Risk for Atherosclerosis? Coronary heart disease (atherosclerosis of the ... Other risk factors can't be controlled. Major Risk Factors Unhealthy blood cholesterol levels . This includes high ...

81

Atherosclerosis in parrots. A review.  

PubMed

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

Bavelaar, F J; Beynen, A C

2004-06-01

82

Atherosclerosis: a classic inflammatory disease.  

PubMed

Atherosclerosis is an inflammatory disease due to a diet high in saturated fat, hypercholesterolemia, obesity, hypoglycemia, etc. mainly mediated by the infiltration of macrophage and T cells into the vascular wall. Once the endothelial is damaged monocytes penetrate the tissue and are transformed in scavenger cells. Upon stimulation of Th1 cells, a group of cytokines is released and contributes to the inflammatory response of atherosclerotic tissue. When macrophages proliferate they amplify inflammatory response through the secretion of growth factors and cytokines such as TNF and IL-1. In addition, chemokines such as RANTES and other C-C chemokines are generated, and matrix metalloprotinease 9 (MMP-9) are produced by activated monocytes. However, the immune system in atherosclerosis still remains unclear. Here, in this study we revisited the inter-relationship between atherosclerosis and inflammation. PMID:22230389

Anogeianaki, A; Angelucci, D; Cianchetti, E; D'Alessandro, M; Maccauro, G; Saggini, A; Salini, V; Caraffa, A; Tete, S; Conti, F; Tripodi, D; Shaik-Dasthagirisaheb, Y B

2011-01-01

83

Oxidized low-density lipoprotein and atherosclerosis  

Microsoft Academic Search

Atherosclerosis is the leading cause of morbidity and mortality in western society. The most important risk factors for atherosclerosis\\u000a include smoking, hypertension, dyslipidemia, diabetes and a family history of premature atherosclerosis. Several studies indicate\\u000a that an increased plasma low density lipoprotein (LDL) cholesterol constitutes a major risk factor for atherosclerosis. Many\\u000a data support a proatherogenic role for oxidized LDL and

S. Devaraj; I. Jialal

1996-01-01

84

Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms.  

PubMed

In contrast to the current belief that cholesterol reduction with statins decreases atherosclerosis, we present a perspective that statins may be causative in coronary artery calcification and can function as mitochondrial toxins that impair muscle function in the heart and blood vessels through the depletion of coenzyme Q10 and 'heme A', and thereby ATP generation. Statins inhibit the synthesis of vitamin K2, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification. Statins inhibit the biosynthesis of selenium containing proteins, one of which is glutathione peroxidase serving to suppress peroxidative stress. An impairment of selenoprotein biosynthesis may be a factor in congestive heart failure, reminiscent of the dilated cardiomyopathies seen with selenium deficiency. Thus, the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs. We propose that current statin treatment guidelines be critically reevaluated. PMID:25655639

Okuyama, Harumi; Langsjoen, Peter H; Hamazaki, Tomohito; Ogushi, Yoichi; Hama, Rokuro; Kobayashi, Tetsuyuki; Uchino, Hajime

2015-03-01

85

Epigenetics in atherosclerosis and inflammation  

PubMed Central

Abstract Atherosclerosis is a multifactorial disease with a severe burden on western society. Recent insights into the pathogenesis of atherosclerosis underscore the importance of chronic inflammation in both the initiation and progression of vascular remodelling. Expression of immunoregulatory molecules by vascular wall components within the atherosclerotic lesions is accordingly thought to contribute to the ongoing inflammatory process. Besides gene regulatory proteins (transcription factors), epigenetic mechanisms also play an essential and fundamental role in the transcriptional control of gene expression. These epigenetic mechanisms change the accessibility of chromatin by DNA methylation and histone modifications. Epigenetic modulators are thus critically involved in the regulation of vascular, immune and tissue-specific gene expression within the atherosclerotic lesion. Importantly, epigenetic processes are reversible and may provide an excellent therapeutic target. The concept of epigenetic regulation is gradually being recognized as an important factor in the pathogenesis of atherosclerosis. Recent research provides an essential link between inflammation and reprogramming of the epigenome. In this review we therefore discuss the basis of epigenetic regulation – and the contribution thereof in the regulation of inflammatory processes in general and during atherosclerosis in particular. Moreover we highlight potential therapeutic interventions based on epigenetic mechanisms. PMID:20132414

Wierda, Rutger J; Geutskens, Sacha B; Jukema, J Wouter; Quax, Paul HA; van den Elsen, Peter J

2010-01-01

86

Avian Atherosclerosis: Retardation by Pectin  

Microsoft Academic Search

A highly significant retardation of spontaneous atherosclerosis was observed in 2-year-old cockerels fed on a standard diet supplemented with 5 percent pectin for 18 months. The pectin-fed birds excreted three times as much lipid extract and almost twice as much cholesterol as did the control cockerels fed the standard diet supplemented with 5 percent nonnutritive fiber.

H. Fisher; P. Griminger; H. S. Weiss; W. G. Siller

1964-01-01

87

FISH AND PROGRESSION OF ATHEROSCLEROSIS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Intakes of fish and long-chain omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) have been of considerable interest for some time due to their effects on heart disease risk reduction. The relationship between fish consumption and progression of coronary atherosclerosis was examined in...

88

Chapter 12. Atherosclerosis and peptic ulcer  

PubMed Central

Aortic and coronary atherosclerosis and the frequency of coronary stenosis and myocardial lesions were studied in subjects with peptic ulcer, in two subgroups with acute and chronic peptic ulcer, and in subjects who had undergone a stomach operation. In all these respects the groups were similar to each other. Men with peptic ulcer had the same amount of aortic atherosclerosis as the standardized average coronary atherosclerosis group but less coronary atherosclerosis, while women with peptic ulcer had less aortic and much less coronary atherosclerosis. The prevalence of coronary stenosis, fresh myocardial infarction, and myocardial scar was very low in those with peptic ulcer, especially in women. PMID:1087198

Sternby, N. H.

1976-01-01

89

Baseline Plasma NT-proBNP and Clinical Characteristics: Results From the Irbesartan in Heart Failure With Preserved Ejection Fraction Trial  

Microsoft Academic Search

BackgroundN-terminal B type natriuretic peptide (NT-proBNP) is usually elevated in heart failure (HF) patients with reduced ejection fraction (EF). Less is known about NT-proBNP in HF with preserved EF (HF-PEF). We measured baseline NT-proBNP in 3562 HF-PEF enrolled patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial.

Robert S. Mckelvie; Michel Komajda; John Mcmurray; Michael Zile; Agata Ptaszynska; Mark Donovan; Peter Carson; Barry M. Massie

2010-01-01

90

Effects of aerobic exercise training and irbesartan on blood pressure and heart rate variability in patients with chronic obstructive pulmonary disease  

PubMed Central

BACKGROUND AND OBJECTIVES: The present pilot study was undertaken to evaluate the efficacy of an aerobic exercise training (AET) program alone or combined with an antihypertensive agent (irbesartan) to reduce blood pressure (BP) and enhance heart rate variability (HRV) in chronic obstructive pulmonary disease patients. METHODS: Twenty-one patients were randomly assigned to a double-blind treatment with exercise and placebo (n=11) or exercise and irbesartan (n=10). Subjects underwent 24 h BP monitoring and 24 h electrocardiographic recording before and after the 12-week AET. HRV was investigated using three indexes from the power spectral analysis and three indexes calculated from the time domain. The AET program consisted of exercising on a calibrated ergocycle for 30 min three times per week. Five patients in the placebo group were excluded during follow-up because they were not compliant. RESULTS: There was no change in 24 h systolic and diastolic BP before (130±14 mmHg and 70±3 mmHg, respectively) and after (128±8 mmHg and 70±8 mmHg, respectively) exercise training in the placebo group, whereas in the irbesartan group systolic and diastolic BP decreased from 135±9 mmHg and 76±9 mmHg to 126±12 mmHg and 72±8 mmHg, respectively (P<0.02). There were no changes in HRV parameters in either group. CONCLUSIONS: The present study suggests that a 12-week AET program is not associated with a significant reduction in BP or enhancement in HRV, whereas an AET program combined with irbe-sartan is associated with a reduction in 24 h BP. PMID:18949104

Marquis, Karine; Maltais, François; Lacasse, Yves; Lacourcière, Yves; Fortin, Claudette; Poirier, Paul

2008-01-01

91

Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension  

PubMed Central

Background Hypertension is one of the major risk factors for cardiovascular and cerebrovascular disease and mortality. Patients who receive insufficient doses of antihypertensive agents or who are poorly adherent to multidrug treatment regimens often fail to achieve adequate blood pressure (BP) control. The aim of this study was to determine the efficacy of an angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) combination tablet containing a regular dose of irbesartan (100 mg) and a high dose of amlodipine (10 mg) with regard to lowering BP and other risk factors for cardiovascular disease. Methods We retrospectively evaluated data from 68 patients with essential hypertension whose treatment regimen was changed either from combination treatment with an independent ARB and a low-dose or regular-dose CCB or from a combination tablet of ARB and a low-dose or regular-dose CCB to a combination tablet containing amlodipine 10 mg and irbesartan 100 mg, because of incomplete BP control. Previous treatments did not include irbesartan as the ARB. Results The combination tablet decreased systolic and diastolic BP. In addition, it significantly decreased serum uric acid, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol levels, independent of the BP-lowering effect. Treatment with the combination tablet did not affect serum triglycerides, plasma glucose, glycated hemoglobin, serum potassium or creatinine levels, or the urinary albumin excretion rate. Conclusion The combination tablet containing amlodipine 10 mg and irbesartan 100 mg had a greater BP-lowering effect than an ARB and a low-dose or regular-dose CCB. In addition, the combination tablet had more favorable effects on serum uric acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels in patients with hypertension. PMID:25624765

Yagi, Shusuke; Takashima, Akira; Mitsugi, Minoru; Wada, Toshihiro; Hotchi, Junko; Aihara, Ken-ichi; Hara, Tomoya; Ishida, Masayoshi; Fukuda, Daiju; Ise, Takayuki; Yamaguchi, Koji; Tobiume, Takeshi; Iwase, Takashi; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Akaike, Masashi; Sata, Masataka

2015-01-01

92

Complex Regulation and Function of the Inflammatory Smooth Muscle Cell Phenotype in Atherosclerosis  

Microsoft Academic Search

Vascular smooth muscle cell (SMC) phenotypic modulation plays a key role in atherosclerosis and is classically defined as a switch from a ‘contractile’ phenotype to a ‘synthetic’ phenotype, whereby genes that define the contractile SMC phenotype are suppressed and proliferation and\\/or migratory mechanisms are induced. There is also evidence that SMCs may take on a ‘proinflammatory’ phenotype, whereby SMCs secrete

Anthony Wayne Orr; Nicole E. Hastings; Brett R. Blackman; Brian R. Wamhoff

2010-01-01

93

Noninvasive Imaging of Carotid Atherosclerosis  

Microsoft Academic Search

\\u000a Carotid atherosclerosis is an important cause of stroke. Because stroke results in considerable morbidity, mortality, and\\u000a costs, prevention is pivotal. Patient symptomatology and degree of luminal stenosis are currently the main grounds to perform\\u000a carotid endarterectomy (CEA). However, many patients undergo CEA with its attendant risks without taking advantage, whereas\\u000a in others CEA is probably incorrectly withheld. Noninvasive imaging of

Robert M. Kwee; Robert J. van Oostenbrugge; Leo Hofstra; Jos M. A. Engelshoven; Werner H. Mess; Joachim E. Wildberger; M. Eline Kooi

94

MRI of subclinical coronary atherosclerosis  

Microsoft Academic Search

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the Western world. Whereas atherosclerosis\\u000a alone is rarely fatal, sudden luminal thrombosis precipitates life-threatening clinical events such as acute coronary syndromes\\u000a and stroke. Plaques assumed to cause luminal thrombosis are referred to as vulnerable plaques, which tend to preserve a normal\\u000a vessel lumen. Today’s clinical assessment of

Christian H. P. Jansen; Marcus R. Makowski; Andrea J. Wiethoff; René M. Botnar

2009-01-01

95

Epigenetics in atherosclerosis: a clinical perspective.  

PubMed

Significant progress has been made in understanding in the pathogenesis of atherosclerosis. Nevertheless, atherosclerosis remains a great threat to human health worldwide. Epigenetic mechanisms, which involve DNA methylation, histone modification, and microRNA, have significantly enhanced our understanding of the pathological process of atherosclerosis. More importantly, epigenetic processes (in contrast to genetic alterations) are reversible and thus provide a potential therapeutic target in atherosclerosis treatment. Both in vitro and in vivo studies using drugs targeting enzymes involved in epigenetic modifications have shown considerable promise in atherosclerosis treatment. This review aims to present an overview of current epigenetic mechanisms involved in the pathogenesis of atherosclerosis, and discuss points in these processes where therapeutic interventions likely bear fruition. PMID:25725221

Zhang, Bi-Kui; Lai, Xin; Jia, Su-Jie

2015-02-01

96

A multimodal Darwinian strategy for alleviating the atherosclerosis pandemic.  

PubMed

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

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

2014-02-01

97

Cholesterol-Lowering Atherosclerosis Study (CLAS)  

ClinicalTrials.gov

Arterial Occlusive Diseases; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Arteriosclerosis; Cerebrovascular Disorders; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Ischemia; Atherosclerosis

2013-12-12

98

Microorganisms in the aetiology of atherosclerosis  

PubMed Central

Recent publications have suggested that infective pathogens might play an important role in the pathogenesis of atherosclerosis. This review focuses on these microorganisms in the process of atherosclerosis. The results of in vitro studies, animal studies, tissue studies, and serological studies will be summarised, followed by an overall conclusion concerning the strength of the association of the microorganism with the pathogenesis of atherosclerosis. The role of the bacteria Chlamydia pneumoniae and Helicobacter pylori, and the viruses human immunodeficiency virus, coxsackie B virus, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and measles virus will be discussed. Key Words: atherosclerosis • Chlamydia pneumoniae • Helicobacter pylori PMID:11041053

Morre, S; Stooker, W; Lagrand, W; van den Brule, A J C; Niessen, H

2000-01-01

99

Multi-Ethnic Study of Atherosclerosis (MESA)  

ClinicalTrials.gov

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

2012-04-26

100

Hypercholesterolemia links hematopoiesis with atherosclerosis  

PubMed Central

Atherosclerosis is characterized by the progressive accumulation of lipids and leukocytes in the arterial wall. Leukocytes such as macrophages accumulate oxidized lipoproteins in the growing atheromata and give rise to foam cells, which can then contribute to a lesion’s necrotic core. Lipids and leukocytes interact also in other important ways. In experimental models, systemic hypercholesterolemia is associated with severe neutrophilia and monocytosis. Recent evidence indicates that cholesterol sensing pathways control the proliferation of hematopoietic stem cell progenitors. Here we review some of the studies that are forging this particular link between metabolism and inflammation and propose several strategies that could target this axis for the treatment of cardiovascular disease. PMID:23228326

Soehnlein, Oliver; Swirski, Filip K.

2015-01-01

101

Therapeutic approaches to drug targets in atherosclerosis  

PubMed Central

Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPAR?, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis. PMID:25061401

Jamkhande, Prasad G.; Chandak, Prakash G.; Dhawale, Shashikant C.; Barde, Sonal R.; Tidke, Priti S.; Sakhare, Ram S.

2013-01-01

102

Scavenger Receptors, Oxidized LDL, and Atherosclerosis  

E-print Network

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

Dennis, Edward A.

103

Molecular link between cholesterol, cytokines and atherosclerosis  

Microsoft Academic Search

Current investigation on the origin of atherosclerosis has initiated an intense debate over whether atherosclerosis results from hypercholesterolemia or an inappropriate immune response to vascular injury. Although the role of the immune system has been questioned, the overwhelming body of evidence clearly indicates that atherogenesis is initiated by the interplay between cholesterol and cellular secretion of cytokines (especially IL-6) and

D. Kaulof

2001-01-01

104

Endothelium Preserving Microwave Treatment for Atherosclerosis  

NASA Technical Reports Server (NTRS)

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.

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

2003-01-01

105

BIOLOGICAL IMAGING OF ATHEROSCLEROSIS: MOVING BEYOND ANATOMY  

PubMed Central

Biological or molecular imaging is now providing exciting new strategies to study atherosclerosis in both animals and humans. These technologies hold the promise to provide disease-specific, molecular information within the context of a systemic or organ-specific disease beyond traditional anatomical-based imaging. By integration of biological, chemical and anatomical imaging knowledge into diagnostic strategies, a more comprehensive and predictive picture of atherosclerosis is likely to emerge. As such, biological imaging is well-positioned to study different stages of atherosclerosis and its treatment, including the sequence of atheroma initiation, progression, and plaque rupture. In this review we describe the evolving concepts in atherosclerosis imaging with a focus on coronary artery disease, and we provide an overview of recent exciting translational developments in biological imaging. The illuminated examples and discussions will highlight how biological imaging is providing new clinical approaches to identify high-risk plaques, and to streamline the development process of new atherosclerosis therapies. PMID:23733542

Verjans, Johan W.; Jaffer, Farouc A.

2013-01-01

106

The autoimmune concept of atherosclerosis  

PubMed Central

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

Grundtman, Cecilia; Wick, Georg

2011-01-01

107

Quantification of carotid vessel atherosclerosis  

NASA Astrophysics Data System (ADS)

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.

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

2006-03-01

108

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 ...

109

Atherosclerosis  

MedlinePLUS

... your diet isn’t enough. Some examples include: Plant sterols and stanols. Plant sterols and stanols can help keep your body ... to get their omega-3 fatty acids from plant sources. For vegetarians, flaxseed oil is a common ...

110

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

PubMed Central

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

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

2014-01-01

111

Platelets and the complement cascade in atherosclerosis  

PubMed Central

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

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

2015-01-01

112

Immune Activation, Immunosenescence, and Osteoprotegerin as Markers of Endothelial Dysfunction in Subclinical HIV-Associated Atherosclerosis  

PubMed Central

HIV-infected patients have a significantly greater risk of cardiovascular disease. Several markers including osteoprotegerin have been shown to be involved in the development and progression of atherosclerosis. We investigated the relationship between T-cell phenotype, osteoprotegerin, and atherosclerosis evaluated by carotid intima-media thickness (c-IMT) in 94 HIV+ patients on suppressive antiretroviral therapy with Framingham score <10%. As for the control group, 24 HIV-negative subjects were enrolled. c-IMT was assessed by ultrasound. CD4+/CD8+ T-cell activation (CD38+ HLADR+) and senescence (CD57+ CD28?) were measured by flow cytometry. IL-6 and OPG levels were measured by ELISA kit. c-IMT was higher in HIV+ than in controls. Among HIV+ patients, 44.7% had pathological c-IMT (?0.9?mm). CD8+ T-cell activation and senescence and OPG plasma levels were higher in HIV+ patients than in controls. Subjects with pathological c-IMT exhibited higher CD8+ immune activation and immunosenescence and OPG levels than subjects with normal c-IMT. Multivariate analysis showed that age, CD8+ CD38+ HLADR+, and CD8+ CD28? CD57+ were independently associated with pathological c-IMT. Several factors have been implicated in the pathogenesis of atherosclerosis in HIV patients. Immune activation and immunosenescence of CD8+ T cell together with OPG plasma levels might be associated with the development and progression of early atherosclerosis, even in the case of viral suppression. PMID:25374442

D'Abramo, Alessandra; Zingaropoli, Maria Antonella; Oliva, Alessandra; D'Agostino, Claudia; Al Moghazi, Samir; De Luca, Giulia; Iannetta, Marco; Mastroianni, Claudio Maria; Vullo, Vincenzo

2014-01-01

113

Atherosclerosis and disturbances in flow.  

PubMed

From experiments on flow in a tapered tube it was found that a ring vortex could be produced in certain circumstances. The parameter which determines the vortex formation is the product of peak reversed flow, Reynolds number, and the taper angle of the tube. Using dimensional analysis, conditions in a model were adjusted to simulate those in the unbranched superficial femoral artery. A vortex was formed when there was sufficiently strong reversed flow, and it did so over a range of nondimensional frequencies similar to those which occur in the artery in humans. When the vortex passes up the tube, the surface stresses oscillate at a frequency an order of magnitude higher than the pulse frequency. It is possible that this oscillating stress could trigger atherosclerosis. The initiating ring vortex could be induced by a slight stenosis distal to the site of atherogenesis. PMID:3228538

Charlesworth, D; Gerrard, J H

1988-01-01

114

Atherosclerosis in Systemic Lupus Erythematosus  

PubMed Central

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

Stojan, George; Petri, Michelle

2015-01-01

115

Macrophage Plasticity in Experimental Atherosclerosis  

PubMed Central

As in human disease, macrophages (MØ) are central players in the development and progression of experimental atherosclerosis. In this study we have evaluated the phenotype of MØ associated with progression of atherosclerosis in the apolipoprotein E (ApoE) knockout (KO) mouse model. We found that bone marrow-derived MØ submitted to M1 and M2 polarization specifically expressed arginase (Arg) II and Arg I, respectively. This distinct arginase expression was used to evaluate the frequency and distribution of M1 and M2 MØ in cross-sections of atherosclerotic plaques of ApoE KO mice. Early lesions were infiltrated by Arg I+ (M2) MØ. This type of MØ favored the proliferation of smooth muscle cells, in vitro. Arg II+ (M1) MØ appeared and prevailed in lesions of aged ApoE KO mice and lesion progression was correlated with the dominance of M1 over the M2 MØ phenotype. In order to address whether the M2->M1 switch could be due to a phenotypic switch of the infiltrated cells, we performed in vitro repolarization experiments. We found that fully polarized MØ retained their plasticity since they could revert their phenotype. The analysis of the distribution of Arg I- and Arg II-expressing MØ also argued against a recent recruitment of M1 MØ in the lesion. The combined data therefore suggest that the M2->M1 switch observed in vivo is due to a conversion of cells already present in the lesion. Our study suggests that interventional tools able to revert the MØ infiltrate towards the M2 phenotype may exert an atheroprotective action. PMID:20111605

Khallou-Laschet, Jamila; Varthaman, Aditi; Fornasa, Giulia; Compain, Caroline; Gaston, Anh-Thu; Clement, Marc; Dussiot, Michaël; Levillain, Olivier; Graff-Dubois, Stéphanie; Nicoletti, Antonino; Caligiuri, Giuseppina

2010-01-01

116

Correlation of Coronary Artery Atherosclerosis with Atherosclerosis of the Intracranial Cerebral Artery and the Extracranial Carotid Artery  

Microsoft Academic Search

Background: Investigating atherosclerosis of the coronary artery in ischemic stroke patients is clinically important because comorbidity is relatively common in such patients. We studied the relationship of atherosclerosis of the coronary artery to atherosclerosis of the intracranial cerebral artery and extracranial carotid artery. Further investigation was performed for determining the factors independently associated with coronary artery atherosclerosis in ischemic stroke

Woo-Keun Seo; Hwan S. Yong; Seong-Beom Koh; Sang-il Suh; Ji H. Kim; Sung-Wook Yu; Ji-Yeon Lee

2008-01-01

117

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

PubMed

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

Miao, Ji; Ling, Alisha V; Manthena, Praveen V; Gearing, Mary E; Graham, Mark J; Crooke, Rosanne M; Croce, Kevin J; Esquejo, Ryan M; Clish, Clary B; Vicent, David; Biddinger, Sudha B

2015-01-01

118

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

PubMed Central

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

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

2015-01-01

119

Macrophages, dendritic cells, and regression of atherosclerosis  

PubMed Central

Atherosclerosis is the number one cause of death in the Western world. It results from the interaction between modified lipoproteins and cells such as macrophages, dendritic cells (DCs), T cells, and other cellular elements present in the arterial wall. This inflammatory process can ultimately lead to the development of complex lesions, or plaques, that protrude into the arterial lumen. Ultimately, plaque rupture and thrombosis can occur leading to the clinical complications of myocardial infarction or stroke. Although each of the cell types plays roles in the pathogenesis of atherosclerosis, the focus of this review will be primarily on the macrophages and DCs. The role of these two cell types in atherosclerosis is discussed, with a particular emphasis on their involvement in atherosclerosis regression. PMID:22934038

Feig, Jonathan E.; Feig, Jessica L.

2012-01-01

120

Neutrophils in atherosclerosis: from mice to man.  

PubMed

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

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

2015-02-01

121

Spectroscopic and spectrofluorimetric studies on the interaction of irbesartan with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and iodine.  

PubMed

Raman, UV-vis, 1H NMR, FT-IR, mass and fluorescence spectral techniques were employed to investigate the mechanism of interaction of irbesartan (IRB) drug with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and iodine. Interaction of IRB with iodine yields triiodide ion and its formation was confirmed by electronic and Raman spectra. The peaks appeared in Raman spectrum of the isolated product at 143, 113 and 76 cm(-1) are assigned to ?as(I-I), ?s(I-I) and ?(I3-) respectively, confirmed the presence of I3- ion. The interaction of DDQ with irbesartan was found to proceed through the formation of outer complex and its conversion to the CT complex. Formation constant (K), molar extinction coefficient (?) and thermodynamic properties ?H#, ?S# and ?G# were determined and discussed. Fluorescence quenching studies indicated that the interaction between the IRB and the acceptors are spontaneous and the IRB-DDQ interaction is found to be stronger than that the other system. Solvent variation studies indicated that the binding constant increased with an increase in polarity of the medium. PMID:21684193

Ganesh, K; Balraj, C; Elango, K P

2011-09-01

122

DNA damage, vascular senescence and atherosclerosis  

Microsoft Academic Search

Atherosclerosis, an intrinsically age-related disease, is attributed to an excessive inflammatory and fibroproliferative process\\u000a that selectively affects arteries. However, premature atherosclerosis is a feature of several human diseases that are known\\u000a to be defective in DNA repair pathways and characterised by predisposition to early onset of age-related diseases. Accordingly,\\u000a there is a growing amount of data demonstrating that oxidative-stress-induced DNA

Maria Grazia Andreassi

2008-01-01

123

Environmental carcinogens and mutational pathways in atherosclerosis.  

PubMed

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

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

2015-05-01

124

Artery regional properties and atherosclerosis susceptibility.  

PubMed

White carneau (WC) pigeons develop spontaneous atherosclerosis in contrast to atherosclerosis-resistant show racer (SR) pigeons. In this study, cellular and extracellular components and smooth muscle cell (SMC) proliferation rates of specific aortic sites were assessed in both breeds of pigeons prior to lesion development. The atherosclerosis-susceptible site of the WC aorta was characterized by larger lumen diameter without accompanying increase in wall thickness, as well as by SMC hypocellularity, increased proteoglycan content and higher elastin content. For both breeds, cells derived from the lesion site had lower proliferation rates compared to proximal aortic control sites. WC cells had greater proliferation rates than SR cells (109% greater at the atherosclerosis-prone site and 133% greater at the control site). Fibroblast growth factor (FGF) increased the proliferation of WC lesion site cells compared to SR cells (79% vs. 35%); whereas, transforming growth factor beta (TGFbeta) reduced growth in SR but not in WC cells. Differences in hemodynamic properties, in cell-matrix, elastin, proteoglycan and proliferation rates of cells and responses to FGF and TGFbeta in cells of the atherosclerosis-prone area have been identified as potential contributors to the enhanced atherosclerosis potential of this site in WC pigeons. PMID:17084416

Wagner, William D; Guo, Feng; Jokinen, Micheal P

2007-01-01

125

Positron Emission Tomography Imaging of Atherosclerosis  

PubMed Central

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

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

2013-01-01

126

AIP1-Mediated Stress Signaling in Atherosclerosis and Arteriosclerosis.  

PubMed

AIP1 (ASK1-interacting protein-1; encoded by the DAB2IP gene), a signaling scaffolding protein, is abundantly expressed in vascular endothelial cells (EC). While it was initially discovered as an apoptosis signal-regulating kinase 1 (ASK1)-interacting protein, AIP1 broadly suppresses inflammatory responses triggered by cytokines and stresses such as TNF, LPS, VEGF, and endoplasmic reticulum (ER) stress in EC (therefore, AIP1 is an anti-inflammatory protein). Human genome-wide association study (GWAS) has identified DAB2IP gene variants conferring susceptibility to cardiovascular diseases. Consistently, a global or vascular EC-specific deletion of DAB2IP in mice strongly enhances inflammatory responses and exacerbates atherosclerosis and graft arteriosclerosis progression in mouse models. Mechanisms for AIP1 function and regulation associated with human cardiovascular diseases need further investigations. PMID:25732743

Zhang, Jiqin; Zhou, Huanjiao Jenny; Ji, Weidong; Min, Wang

2015-05-01

127

The protective effect of the RAS inhibitor on diabetic patients with nephropathy in the context of VEGF suppression  

PubMed Central

Aim: The aim of the present study was to explore whether renin angiotensin system (RAS) inhibitor can reduce the production of vascular endothelium growth factor (VEGF). Further, we sought to elucidate the correlation between VEGF level and certain clinical parameters, such as albumin excretion rate (AER), before and after treatment with angiotensin type 1 receptor blocker. Methods: We recruited 166 type 2 diabetic patients at various stages of diabetic nephropathy (DN) and 46 healthy control subjects for a cross-sectional study. We recruited another 42 hypertensive type 2 diabetic patients with microalbuminuria for a longitudinal study involving a 6-month irbesartan treatment protocol. Urinary VEGF (uVEGF) levels were determined using ELISA. Results: In the cross-sectional study, hypertensive type 2 diabetic patients who received RAS inhibitor presented lower uVEGF levels than those who did not receive the RAS inhibitor. Statistical analysis indicated that uVEGF level was independently correlated with the AER. In the longitudinal study involving the 6-month irbesartan treatment, we demonstrated that uVEGF levels decreased significantly in patients who achieved a 50% AER reduction (remission group, n=32). In contrast, uVEGF levels remained unchanged in patients who did not exhibit a 50% AER reduction (nonremission group, n=10). Furthermore, the change in uVEGF was significantly correlated with the change in AER (r=0.65, P<0.01) before and after 6 months of irbesartan treatment. This result held true even after we had adjusted for the decrease in average blood pressure. Conclusion: The protective effect of the RAS inhibitor in DN patients is associated with the suppression of VEGF. Accordingly, it may be possible to use uVEGF as a marker of DN progression. We suggest that uVEGF may be an important target for therapeutic intervention in the context of DN. PMID:19169272

Chen, Hai-bing; Lu, Jun-xi; Li, Qing; Bao, Yu-qian; Tang, Jun-ling; Lu, Hui-juan; Xiang, Kun-san; Jia, Wei-ping

2009-01-01

128

Atherosclerosis: Process, Indicators, Risk Factors and New Hopes  

PubMed Central

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

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

2014-01-01

129

Gene delivery of suppressors of cytokine signaling (SOCS) inhibits inflammation and atherosclerosis development in mice.  

PubMed

Chronic activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway contributes to vascular inflammation and atherosclerosis by inducing expression of genes involved in cell proliferation, differentiation and migration. We aimed to investigate whether enforced expression of negative regulators, the suppressors of cytokine signaling (SOCS1 and SOCS3), inhibits harmful JAK/STAT-mediated responses and affects atherosclerosis in apolipoprotein E knockout mice. Adenovirus-mediated SOCS1 transgene expression impaired the onset and progression of atherosclerosis without impact on lipid profile, whereas SOCS3 was only effective on early atherosclerosis. Mechanistically, SOCS gene delivery, primarily SOCS1, attenuated STAT1 and STAT3 activation and reduced the expression of STAT-dependent genes (chemokine/chemokine receptors, adhesion molecules, pro-inflammatory cytokines and scavenger receptors) in aortic tissue. Furthermore, atherosclerotic plaques exhibit a more stable phenotype characterized by lower lipids, T cells and M1 macrophages and higher M2 macrophages and collagen. Atheroprotection was accompanied by a systemic alteration of T helper- and T regulatory-related genes and a reduced activation state of circulating monocytes. In vascular smooth muscle cells and macrophages, SOCS gene delivery inhibited cytokine-induced STAT activation, pro-inflammatory gene expression, cell migration and proliferation. In conclusion, targeting SOCS proteins, predominantly SOCS1, to suppress pathological mechanisms involved in atheroma plaque progression and destabilization could be an interesting anti-atherosclerotic strategy. PMID:25604439

Recio, Carlota; Oguiza, Ainhoa; Mallavia, Beñat; Lazaro, Iolanda; Ortiz-Muñoz, Guadalupe; Lopez-Franco, Oscar; Egido, Jesus; Gomez-Guerrero, Carmen

2015-03-01

130

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

PubMed Central

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

Eren, Esin; Yilmaz, Necat; Aydin, Ozgur

2013-01-01

131

Atherosclerosis and the role of immune cells.  

PubMed

Atherosclerosis is a chronic inflammatory disease arising from lipids, specifically low-density lipoproteins, and leukocytes. Following the activation of endothelium with the expression of adhesion molecules and monocytes, inflammatory cytokines from macrophages, and plasmacytoid dendritic cells, high levels of interferon (IFN)-? and ? are generated upon the activation of toll-like receptor-9, and T-cells, especially the ones with Th1 profile, produce pro-inflammatory mediators such as IFN-? and upregulate macrophages to adhere to the endothelium and migrate into the intima. This review presents an exhaustive account for the role of immune cells in the atherosclerosis. PMID:25879006

Ilhan, Fulya; Kalkanli, Sevgi Tas

2015-04-16

132

Atherosclerosis and the role of immune cells  

PubMed Central

Atherosclerosis is a chronic inflammatory disease arising from lipids, specifically low-density lipoproteins, and leukocytes. Following the activation of endothelium with the expression of adhesion molecules and monocytes, inflammatory cytokines from macrophages, and plasmacytoid dendritic cells, high levels of interferon (IFN)-? and ? are generated upon the activation of toll-like receptor-9, and T-cells, especially the ones with Th1 profile, produce pro-inflammatory mediators such as IFN-? and upregulate macrophages to adhere to the endothelium and migrate into the intima. This review presents an exhaustive account for the role of immune cells in the atherosclerosis. PMID:25879006

Ilhan, Fulya; Kalkanli, Sevgi Tas

2015-01-01

133

Macrophages in atherosclerosis: a dynamic balance  

PubMed Central

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

Moore, Kathryn; Sheedy, Frederick; Fisher, Edward

2015-01-01

134

The role of heat shock protein 90 in migration and proliferation of vascular smooth muscle cells in the development of atherosclerosis.  

PubMed

The molecular chaperone heat shock protein 90 (HSP90) is overexpressed in plaques of atherosclerosis patients, and is associated with plaque instability. However, the role of HSP90 in atherosclerosis remains unclear. The present study investigated the effects of HSP90 inhibition on migration and proliferation of vascular smooth muscle cells (VSMCs) and involvement in atherosclerosis. To examine the role of HSP90 in VSMC migration, VSMCs were treated with the specific HSP90 inhibitors, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) and STA-9090. Results of a chemotaxis assay showed that the HSP90 inhibitors suppress migration of VSMCs. HSP90 inhibition also prevented invasion and sprout formation of VSMCs via inhibition of matrix metalloproteinase-2 proteolytic activity. Results of a flow cytometric analysis showed that HSP90 inhibition induces cell cycle arrest via regulation of cyclin D3, PCNA and pRb. To investigate the role of HSP90 in the development of atherosclerosis, low-density lipoprotein receptor (LDLR) deficient mice were fed with a high cholesterol diet for 4weeks and treated with 17-AAG for 8weeks. HSP90 inhibition suppressed migration of VSMCs into atherosclerotic plaque lesions in high cholesterol diet-stimulated LDLR(-/-) mice. Inhibition of HSP90 attenuates formation of atherosclerotic plaques via suppression of VSMC migration and proliferation, indicating that HSP90 inhibitors can be used as therapeutic agents for atherosclerosis and in stent restenosis. PMID:24650873

Kim, Jeonghan; Jang, Sung-Wuk; Park, Eunsoo; Oh, Minseok; Park, Sodam; Ko, Jesang

2014-07-01

135

Diabetes and Progression of Carotid Atherosclerosis The Insulin Resistance Atherosclerosis Study  

Microsoft Academic Search

Objective—We sought to determine the rate of progression of carotid atherosclerosis in persons with normal glucose tolerance, impaired glucose tolerance, and undiagnosed and diagnosed type 2 diabetes. Methods and Results—The Insulin Resistance Atherosclerosis Study (IRAS) is an observational cohort study in which 1192 men and women were examined at a 5-year interval. Participants of 3 ethnic groups (non-Hispanic white, African

Lynne E. Wagenknecht; Daniel Zaccaro; Mark A. Espeland; Andrew J. Karter; Daniel H. O'Leary; Steven M. Haffner

2010-01-01

136

Ventilatory Chaos Is Impaired in Carotid Atherosclerosis  

Microsoft Academic Search

Ventilatory chaos is strongly linked to the activity of central pattern generators, alone or influenced by respiratory or cardiovascular afferents. We hypothesized that carotid atherosclerosis should alter ventilatory chaos through baroreflex and autonomic nervous system dysfunctions. Chaotic dynamics of inspiratory flow was prospectively evaluated in 75 subjects undergoing carotid ultrasonography: 27 with severe carotid stenosis (>70%), 23 with moderate stenosis

Laurence Mangin; Guy Lesèche; Alain Duprey; Christine Clerici

2011-01-01

137

Therapeutic targeting of chemokine interactions in atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a chronic inflammatory disease of the arterial wall that is characterized by a disturbed equilibrium of immune responses and lipid accumulation, leading to the development of plaques. The atherogenic influx of mononuclear cells is orchestrated by chemokines and their receptors. Studies using gene-deficient mice and antagonists based on peptides and small molecules have generated insight into targeting chemokine–receptor

Rory R. Koenen; Christian Weber

2010-01-01

138

Immune and Inflammatory Mechanisms of Atherosclerosis*  

PubMed Central

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

Galkina, Elena; Ley, Klaus

2009-01-01

139

Cannabinoids for therapeutic use in atherosclerosis 1  

Microsoft Academic Search

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

Sabine Steffens

2006-01-01

140

Inflammation, Atherosclerosis, and Coronary Artery Disease  

Microsoft Academic Search

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

Göran K. Hansson

2005-01-01

141

Metabolomic analyses for atherosclerosis, diabetes, and obesity  

PubMed Central

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

2013-01-01

142

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...

143

Macrophages heterogeneity in atherosclerosis – implications for therapy  

PubMed Central

Abstract Atherosclerosis is a chronic inflammatory disease occurring within the artery wall and is an underlying cause of cardiovascular complications, including myocardial infarction, stroke and peripheral vascular disease. Its pathogenesis involves many immune cell types with a well accepted role for monocyte/macrophages. Cholesterol-loaded macrophages are a characteristic feature of plaques and are major players in all stages of plaque development. As well as modulating lipid metabolism, macrophages secrete inflammatory cytokines, chemokines and reactive oxygen and nitrogen species that drive pathogenesis. They also produce proteases and tissue factor that contribute to plaque rupture and thrombosis. Macrophages are however heterogeneous cells and when appropriately activated, they phagocytose cytotoxic lipoproteins, clear apoptotic bodies, secrete anti-inflammatory cytokines and synthesize matrix repair proteins that stabilize vulnerable plaques. Pharmacological modulation of macrophage activity therefore represents a potential therapeutic strategy for atherosclerosis. The aim of this review is to provide an overview of the current understanding of the different macrophage subsets and their monocyte precursors, and, the implications of these subsets for atherosclerosis. This will present a foundation for highlighting novel opportunities to exploit the heterogeneity of macrophages as important diagnostic and therapeutic targets for atherosclerosis and its associated diseases. PMID:20629993

Wilson, Heather M

2010-01-01

144

Insulin resistance, metabolic stress, and atherosclerosis  

PubMed Central

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

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

2012-01-01

145

Infectious burden and atherosclerosis: A clinical issue  

PubMed Central

Atherosclerotic cardiovascular diseases, chronic inflammatory diseases of multifactorial etiology, are the leading cause of death worldwide. In the last decade, more infectious agents, labeled as “infectious burden”, rather than any single pathogen, have been showed to contribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae (C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet aggregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule production. Others, such as Helicobacter pylori (H. pylori), influenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall (e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents (such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may contribute to atherosclerosis, defining the interplay of more infectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be amplified. Clearly, continued research and a greater awareness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis. PMID:25032197

Sessa, Rosa; Pietro, Marisa Di; Filardo, Simone; Turriziani, Ombretta

2014-01-01

146

Endothelial MicroRNAs and Atherosclerosis  

PubMed Central

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

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

2013-01-01

147

Mutations of mitochondrial genome in carotid atherosclerosis  

PubMed Central

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.

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

148

Computer assessment of atherosclerosis from angiographic images  

NASA Technical Reports Server (NTRS)

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

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

1982-01-01

149

Restricted Protein Intake and Avian Atherosclerosis  

Microsoft Academic Search

ALTHOUGH low-protein diets in the presence or absence of supplementary dietary cholesterol give rise to a marked hypercholesterolaemia in Leghorn cocks, nevertheless, we observed1,2 a reduction in the severity of abdominal atherosclerosis after 10 or 20 weeks on the experimental low-protein diets. We have examined the effects of prolonged restrictions (20 months) of protein intake in relation to plasma cholesterol,

Hans Fisher; W. G. Siller; P. Griminger

1965-01-01

150

ADAMTS proteases: key roles in atherosclerosis?  

Microsoft Academic Search

The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteases are secreted enzymes that regulate extracellular\\u000a matrix turnover by degrading specific matrix components. Roles for the proteases in inflammation and atherosclerosis have\\u000a been suggested by a number of recent studies, and the role of ADAMTS-4 and -5 in the breakdown of aggrecan and subsequent\\u000a degradation of cartilage during osteoarthritis has

Rebecca C. Salter; Tim G. Ashlin; Alvin P. L. Kwan; Dipak P. Ramji

2010-01-01

151

ORAL HEALTH, ATHEROSCLEROSIS, AND CARDIOVASCULAR DISEASE  

Microsoft Academic Search

During the last two decades, there has been an increasing interest in the impact of oral health on atherosclerosis and subsequent cardiovascular disease (CVD). The advent of the inflammation paradigm in coronary pathogenesis stimulated research in chronic infections caused by a variety of micro-organisms—such as Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus—as well as dental pathogens, since these chronic infections are

Jukka H. Meurman; Mariano Sanz; Sok-Ja Janket

152

Pentraxins, Anti-pentraxin Antibodies, and Atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a disease of the vascular wall, which predominantly affects large and medium-sized arteries. It represents\\u000a a leading cause of morbidity and mortality in the Western world. In the last few decades, it has been clearly shown that immune\\u000a system plays a relevant role in atherogenesis. The effectors of both innate and adaptive immunity, including immune cells,\\u000a cell or

N. Bassi; S. Zampieri; A. Ghirardello; M. Tonon; M. Zen; F. Cozzi; A. Doria

2009-01-01

153

Hormones and coronary atherosclerosis in women  

Microsoft Academic Search

Heart disease is the major health issue facing women in the United States today. Yet, less than 50% of women are aware cardiovascular\\u000a disease is a health problem. Atherosclerosis begins in childhood and lipid streaks have been identified in girls ages 15–19\\u000a in the abdominal aorta and the right coronary artery. Risk factors for cardiovascular disease in women include smoking,

Charles E. Rackley

2004-01-01

154

Hyaluronic acid nanoparticles for active targeting atherosclerosis.  

PubMed

For the effective diagnosis and therapy of atherosclerosis, there is a pressing need to develop the carrier which can specifically deliver the agents to the pathological site. Since the representative hallmark of atherosclerosis in its pathogenic process is the over-expression of the receptors for hyaluronic acid (HA) such as stabilin-2 and CD44, we herein investigated the potential of HA nanoparticles (HA-NPs) as the carrier for active targeting atherosclerosis. From in vitro cellular uptake tests, it was revealed that HA-NPs were selectively taken up by the cells over-expressing stabilin-2 or CD44. On the other hand, the cellular uptake of HA-NPs was drastically reduced when the cells were pre-treated with excess amount of free HA, implying that HA-NPs were taken up by the receptor-mediated endocytosis. Following systemic administration of Cy5.5-labeled NPs into the ApoE-deficient mice as the animal model, the atherosclerotic legion was assessed at 24 post-injection by using the optical imaging system. Interestingly, the fluorescent signal of the atherosclerotic lesion by HA-NPs was much stronger than that of the normal aorta. Three dimensional z-stack images of an atherosclerotic plaque indicated the even distribution of HA-NPs in the atherosclerotic legion. It was demonstrated by immunohistochemistry that HA-NPs were co-localized with the HA receptors including stabilin-2 and CD44. In addition, the amount of HA-NPs, accumulated in the atherosclerotic lesion, was much higher than that of HGC-NPs, known to reach the atherosclerotic lesion by the passive targeting mechanism. Overall, it was evident that HA-NPs could effectively reach the atherosclerotic lesion via the active targeting mechanism after systemic administration, implying their high potential as the carrier for diagnosis and therapy of atherosclerosis. PMID:25890732

Lee, Ga Young; Kim, Jong-Ho; Choi, Ki Young; Yoon, Hong Yeol; Kim, Kwangmeyung; Kwon, Ick Chan; Choi, Kuiwon; Lee, Byung-Heon; Park, Jae Hyung; Kim, In-San

2015-06-01

155

Oral Health, Atherosclerosis, and Cardiovascular Disease  

Microsoft Academic Search

During the last two decades, there has been an increasing interest in the impact of oral health on atherosclerosis and subsequent cardiovascular disease (CVD). The advent of the inflammation paradigm in coronary pathogenesis stimulated research in chronic infections caused by a variety of micro-organisms—such as Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus—as well as dental pathogens, since these chronic infections are

Jukka H. Meurman; Mariano Sanz; Sok-Ja Janket

2004-01-01

156

[Mitogen-activated protein kinases in atherosclerosis].  

PubMed

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

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

2014-01-01

157

Tissue specific up regulation of ACE2 in rabbit model of atherosclerosis by atorvastatin: role of epigenetic histone modifications.  

PubMed

Growing body of evidence points out the crucial role of ACE2 in preventing atherosclerosis. However, data on how atherosclerosis affects ACE2 expression in heart and kidney remains unknown. Atherosclerosis was induced by feeding New Zealand White rabbits with high cholesterol diet (HCD - 2%) for 12 weeks and atorvastatin was administered (5mg/kg/day p.o) in last 3 weeks. ACE2 mRNA and protein expression was assessed by Western blotting and real time PCR. HCD fed rabbits developed atherosclerosis as confirmed by increase in plasma total cholesterol, LDL and triglycerides as well as formation atherosclerotic plaques in arch of aorta. The ACE2 protein but not mRNA expression was reduced in heart and kidney of HCD rabbits. Interestingly, atorvastatin increased the ACE2 protein expression in heart and kidney of HCD rabbits. However, atorvastatin increased ACE2 mRNA in heart but not in kidney of HCD rabbits. Atorvastatin increased the occupancy of histone H3 acetylation (H3-Ac) mark on ACE2 promoter region in heart of HCD rabbits indicating direct or indirect epigenetic up-regulation of ACE2 by atorvastatin. Further, atorvastatin suppressed Ang II-induced contractile responses and enhanced AT2 receptor mediated relaxant responses in atherosclerotic aorta. We propose that atherosclerosis is associated with reduced ACE2 expression in heart and kidney. We also show an unexplored potential of atorvastatin to up-regulate ACE2 via epigenetic histone modifications. Our data suggest a novel way of replenishing ACE2 expression for preventing not only atherosclerosis but also other cardiovascular disorders. PMID:25482567

Tikoo, Kulbhushan; Patel, Gaurang; Kumar, Sandeep; Karpe, Pinakin Arun; Sanghavi, Maitri; Malek, Vajir; Srinivasan, K

2015-02-01

158

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

PubMed Central

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

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

2012-01-01

159

Animal models for the atherosclerosis research: a review.  

PubMed

Atherosclerosis is a leading cause of death worldwide, and its mechanisms are still unclear. However, various animal models have significantly advanced our understanding of the mechanisms involved in atherosclerosis and have allowed the evaluation of therapeutic options. The aim of this paper is to review those animal models (i.e., rabbits, mice, rats, guinea pigs, hamsters, avian, carnivores, swine, and, non-human primates) that have been used to study atherosclerosis. Though there is no single perfect animal model that completely replicates the stages of human atherosclerosis, cholesterol feeding and mechanical endothelial injury are two common features shared by most models of atherosclerosis. Further, with the development of genetically modified animals, these models are significantly broadening our understanding of the pathogenesis of atherosclerosis. PMID:21468891

Xiangdong, Li; Yuanwu, Liu; Hua, Zhang; Liming, Ren; Qiuyan, Li; Ning, Li

2011-03-01

160

The role of the vascular dendritic cell network in atherosclerosis  

PubMed Central

A complex role has been described for dendritic cells (DCs) in the potentiation and control of vascular inflammation and atherosclerosis. Resident vascular DCs are found in the intima of atherosclerosis-prone vascular regions exposed to disturbed blood flow patterns. Several phenotypically and functionally distinct vascular DC subsets have been described. The functional heterogeneity of these cells and their contributions to vascular homeostasis, inflammation, and atherosclerosis are only recently beginning to emerge. Here, we review the available literature, characterizing the origin and function of known vascular DC subsets and their important role contributing to the balance of immune activation and immune tolerance governing vascular homeostasis under healthy conditions. We then discuss how homeostatic DC functions are disrupted during atherogenesis, leading to atherosclerosis. The effectiveness of DC-based “atherosclerosis vaccine” therapies in the treatment of atherosclerosis is also reviewed. We further provide suggestions for distinguishing DCs from macrophages and discuss important future directions for the field. PMID:23552284

Alberts-Grill, Noah; Denning, Timothy L.; Rezvan, Amir

2013-01-01

161

Vascular respiratory uncoupling increases blood pressure and atherosclerosis  

Microsoft Academic Search

The observations that atherosclerosis often occurs in non-smokers without elevated levels of low-density lipoprotein cholesterol, and that most atherosclerosis loci so far identified in mice do not affect systemic risk factors associated with atherosclerosis, suggest that as-yet-unidentified mechanisms must contribute to vascular disease. Arterial walls undergo regional disturbances of metabolism that include the uncoupling of respiration and oxidative phosphorylation, a

Carlos Bernal-Mizrachi; Allison C. Gates; Sherry Weng; Takuji Imamura; Russell H. Knutsen; Pascual Desantis; Trey Coleman; R. Reid Townsend; Louis J. Muglia; Clay F. Semenkovich

2005-01-01

162

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

PubMed

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

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

163

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

PubMed Central

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

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

2014-01-01

164

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

SciTech Connect

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

Nitta, Norihisa, E-mail: r34nitta@belle.shiga-med.ac.jp; Seko, Ayumi; Sonoda, Akinaga; Ohta, Shinichi; Tanaka, Toyohiko; Takahashi, Masashi; Murata, Kiyoshi [Shiga University of Medical Science, Department of Radiology (Japan); Takemura, Shizuki [Shiga University of Medical Science, Department of Pathology (Japan); Sakamoto, Tsutomu [Koka General Hospital, Department of Radiology (Japan); Tabata, Yasuhiko [Kyoto University, Department of Biomaterials, Field of Tissue Engineering (Japan)

2008-03-15

165

Indoleamine 2,3-dioxygenase enzyme activity correlates with risk factors for atherosclerosis: the Cardiovascular Risk in Young Finns Study  

PubMed Central

Indoleamine 2,3 dioxygenase (IDO), an enzyme involved in the catabolism of tryptophan, suppresses T cell activity and is up-regulated by various inflammatory stimuli. The ratio of kynurenine, the main metabolite of tryptophan, to tryptophan (kyn/trp) reflects IDO activity. We calculated IDO activity and measured carotid intima-media thickness (IMT), a presymptomatic predictor of atherosclerosis, in 986 young adults (544 female, 442 male) for whom data on levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, high sensitive C-reactive protein (CRP), body mass index (BMI), waist circumference, waist-to-hip ratio, systolic and diastolic blood pressure and smoking habits were available. IDO activity correlated significantly with IMT in female subjects, but not in males. In a multivariate linear regression model, IDO did not correlate independently with IMT in female subjects. However, IDO activity correlated significantly with several risk factors for atherosclerosis in females, i.e. with age, LDL-C, BMI, weakly with CRP and inversely with HDL-C and triglyceride. In males IDO activity correlated significantly with CRP and inversely with HDL-C. In conclusion, our results suggest that the IDO enzyme is involved in the immune regulation of early atherosclerosis, particularly in young female adults, and could constitute a novel marker of immune activation in early atherosclerosis in females. PMID:17349013

Pertovaara, M; Raitala, A; Juonala, M; Lehtimäki, T; Huhtala, H; Oja, S S; Jokinen, E; Viikari, J S A; Raitakari, O T; Hurme, M

2007-01-01

166

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

PubMed Central

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

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

2015-01-01

167

Elevated serum neopterin levels in atherosclerosis.  

PubMed

Plasma levels of neopterin were determined in patients with different clinical stages of atherosclerosis. Non-hospitalized patients with atherosclerosis had serum and plasma neopterin levels within the normal range of the assay (6 +/- 2 nM). These values were not significantly different from those reported for healthy blood donors (5 +/- 2 nM). In contrast, about 50% (29 out of 61) of hospitalized patients undergoing conservative or surgical therapy had neopterin plasma levels, which exceeded the normal range (greater than 10 nM) up to 10-fold. The two groups differ on a significance level of P less than 0.01. For further evaluation hospitalized patients were subgrouped according to neopterin levels. In the subgroup with elevated neopterin levels patients with higher Frederickson types of atherosclerosis were overrepresented compared to patients with normal neopterin levels. Type 4 differed significantly from patients without pathological changes of lipoprotein (P less than 0.05). Only 3 patients suffered from minimal skin necrosis, two of them had elevated neopterin levels. Significantly more patients with peripheral artery occlusions had elevated neopterin levels than patients with occlusions of central arteries (P less than 0.05). All other criteria used for comparison (sex, age, smoking, antioxidant status, diabetes, hypertension, adipositas, hyperuricemia) did not vary significantly in both subgroups. These data indicate that neopterin plasma levels might be a valuable parameter in activity staging and therapeutic follow up of atherosclerotic patients. Additionally, an involvement of the nonspecific immune system in atherogenesis is suggested by the increased plasma neopterin concentrations. PMID:1793448

Tatzber, F; Rabl, H; Koriska, K; Erhart, U; Puhl, H; Waeg, G; Krebs, A; Esterbauer, H

1991-08-01

168

Association of Fat Density With Subclinical Atherosclerosis  

PubMed Central

Background Ectopic fat density is associated with cardiovascular disease (CVD) risk factors above and beyond fat volume. Volumetric measures of ectopic fat have been associated with CVD risk factors and subclinical atherosclerosis. The aim of this study was to investigate the association between fat density and subclinical atherosclerosis. Methods and Results Participants were drawn from the Multi?Detector Computed Tomography (MDCT) substudy of the Framingham Heart Study (n=3079; mean age, 50.1 years; 49.2% women). Fat density was indirectly estimated by computed tomography attenuation (Hounsfield Units [HU]) on abdominal scan slices. Visceral fat (VAT), subcutaneous fat (SAT), and pericardial fat HU and volumes were quantified using standard protocols; coronary and abdominal aortic calcium (CAC and AAC, respectively) were measured radiographically. Multivariable?adjusted logistic regression models were used to evaluate the association between adipose tissue HU and the presence of CAC and AAC. Overall, 17.1% of the participants had elevated CAC (Agatston score [AS]>100), and 23.3% had elevated AAC (AS>age?/sex?specific cutoffs). Per 5?unit decrement in VAT HU, the odds ratio (OR) for elevated CAC was 0.76 (95% confidence interval [CI], 0.65 to 0.89; P=0.0005), even after adjustment for body mass index or VAT volume. Results were similar for SAT HU. With decreasing VAT HU, we also observed an OR of 0.79 (95% CI, 0.67 to 0.92; P=0.004) for elevated AAC after multivariable adjustment. We found no significant associations between SAT HU and AAC. There was no significant association between pericardial fat HU and either CAC or AAC. Conclusions Lower VAT and SAT HU, indirect estimates of fat quality, are associated with a lower risk of subclinical atherosclerosis. PMID:25169793

Alvey, Nicholas J.; Pedley, Alison; Rosenquist, Klara J.; Massaro, Joseph M.; O'Donnell, Christopher J.; Hoffmann, Udo; Fox, Caroline S.

2014-01-01

169

Quest for New Biomarkers in Atherosclerosis  

PubMed Central

The Cho and Baldan labs focus their efforts on novel pathways that control atherogenesis. MIF (Macrophage migration inhibitory factor) recruits macrophages to atherosclerotic lesions and activates the production of matrix proteinases, which in turn destabilize atherosclerotic plaques. On the other hand, miR-33 coordinates the expression of several sterol transporters essential for high-density lipoprotein metabolism and bile secretion. Thus, both MIF and miR-33 are promising therapeutic targets to manage patients at risk of developing atherosclerosis. PMID:24003651

Cho, Yoonsang; Baldán, Ángel

2013-01-01

170

Chlamydia pneumoniae — an infectious risk factor for atherosclerosis?  

Microsoft Academic Search

Cardiovascular disease, of which atherosclerosis is an important component, is the leading cause of death in the western world. Although there are well-defined risk factors for atherosclerosis, these factors do not account for all incidences of the disease. Because atherosclerotic processes are typified by chronic inflammatory responses, which are similar to those that are elicited by chronic infection, the role

Cho-cho Kuo; Lee Ann Campbell

2004-01-01

171

Ambient Air Pollution and Atherosclerosis in Los Angeles  

Microsoft Academic Search

Associations have been found between long-term exposure to ambient air pollution and cardiovascular morbidity and mortality. The contribution of air pollution to atherosclerosis that underlies many cardiovascular diseases has not been investigated. Animal data suggest that ambient particulate matter (PM) may contribute to atherogenesis. We used data on 798 participants from two clinical trials to investigate the association between atherosclerosis

Nino Künzli; Michael Jerrett; Wendy J. Mack; Bernardo Beckerman; Laurie LaBree; Frank Gilliland; Duncan Thomas; John Peters; Howard N. Hodis

2004-01-01

172

Role of DNA damage in atherosclerosis--bystander or participant?  

PubMed

Atherosclerosis leading to cardiovascular disease is the leading cause of death among western populations. Atherosclerosis in characterised by the development of a fibrofatty lesion that consists of a diverse cell population, including inflammatory cells that create an intensely oxidising environment within the vessel. Coupled with normal replication, the local intracellular and extracellular environment causes damage to cellular DNA that is recognised and repaired by the DNA damage response (DDR) pathway. The role of DNA damage and the resulting deregulation of 'normal' cellular behaviour and subsequent loss of cell cycle control checkpoints have been widely studied in cancer. However, despite the extensive evidence for DNA damage in atherosclerosis, it is only over the past two decades that a causative link between DNA damage and atherosclerosis has been hypothesised. Whilst atherosclerosis is a feature of human disease characterised by defects in DNA damage, currently the role of DNA damage in the initiation and progression of atherosclerosis remains highly debated, as a 'chicken and egg' situation. This review will analyse the evidence for, the causes of, and consequences of DNA damage in atherosclerosis, detail the DNA damage response pathway that results in these consequences, and highlight therapeutic opportunities in this area. We also outline the evidence that DNA damage is a cause of both initiation and progression of atherosclerosis, and not just a consequence of disease. PMID:21726542

Gray, Kelly; Bennett, Martin

2011-10-01

173

Modulation of atherosclerosis by N-3 polyunsaturated fatty acids  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

174

The immune response in atherosclerosis: a double-edged sword  

Microsoft Academic Search

Immune responses participate in every phase of atherosclerosis. There is increasing evidence that both adaptive and innate immunity tightly regulate atherogenesis. Although improved treatment of hyperlipidaemia reduces the risk for cardiac and cerebral complications of atherosclerosis, these remain among the most prevalent of diseases and will probably become the most common cause of death globally within 15 years. This Review

Göran K. Hansson; Peter Libby

2006-01-01

175

MicroRNA-125b is involved in atherosclerosis obliterans in vitro by targeting podocalyxin.  

PubMed

Cardiovascular disease associated with oxidative stress, including atherosclerosis, is the leading cause of mortality worldwide. The accelerated proliferation and migration of vascular smooth muscle cells are the predominant characteristics of atherogenesis, and endothelial dysfunction is a major risk factor for the pathogenesis of atherosclerosis. Podocalyxin (PODXL), a type I member of the cluster of differentiation 34 family of sialomucins, functions as a pro?adhesive molecule. Emerging evidence has revealed the importance of micro (mi)RNAs in the cardiovascular system. The present study demonstrated that there was an inverse association between miRNA (miR)?125b and PODXL in human umbilical vein endothelial cells and human aortic vascular smooth muscle cells (HAVSMCs) treated with oxidized low?density lipoprotein (LDL) and platelet derived growth factor. Additionally, miR?125b had a suppressive function in cell proliferation and migration, at least partially via targeting PODXL in the HAVSMCs. Furthermore, the data suggested that the functions of miR?125b in arteriosclerosis obliterans may be associated with transgelin, lectin?type oxidized LDL receptor?1, vascular endothelial?cadherin, intercellular adhesion molecule?1, interleukin?6 and monocyte chemotactic protein?1. In conclusion, miR?125b was found to be important in arteriosclerosis obliterans by suppressing the expression of PODXL and may serve as a potential therepeutic target for the treatment of arteriosclerosis obliterans. PMID:25738314

Li, Xiaobing; Yao, Na; Zhang, Juan; Liu, Zhenjiang

2015-07-01

176

High phosphate diet reduces atherosclerosis formation in apolipoprotein E-deficient mice  

PubMed Central

Although higher serum phosphate level is a risk factor for cardiovascular diseases in general population as well as chronic kidney disease patients, it has not been clarified whether higher phosphate can affect atherosclerotic plaque formation. In this study, we investigated the effect of prolonged-intake of different concentrations of phosphate on atherosclerosis formation using apolipoprotein E-deficient mice. Apolipoprotein E-deficient mice were fed with high fat diet including 0.6%, 1.2% or 1.8% phosphate. After 20-week treatment, atherosclerotic plaque formation in aorta in 1.8% phosphate diet group was unexpectedly less than that in the other groups. To elucidate mechanisms of suppression of plaque formation by high phosphate diet, we hypothesized that high phosphate diet may modify a profile of monocytes/macrophages suppressing plaque formation. We confirmed that elevated peripheral monocytes (CD11b+, F4/80+ cell numbers) in apolipoprotein E-deficient mice were decreased by feeding with 1.8% P diet. In addition, ex vivo study indicated that high dose of phosphate induced macrophage apoptosis. These observations suggest that excess phosphate intake decreased atherosclerosis formation, at least in part, by changing the profile of peripheral monocytes or inducing apoptosis of macrophages in apolipoprotein E-deficient mice. PMID:21980226

Shiota, Asuka; Taketani, Yutaka; Maekawa, Yoichi; Yasutomo, Koji; Sata, Masataka; Sakai, Tohru; Mizuno, Risuke; Isshiki, Masashi; Yamamoto, Hironori; Takeda, Eiji

2011-01-01

177

Testing the iron hypothesis in a mouse model of atherosclerosis  

PubMed Central

SUMMARY Hepcidin, the iron-regulatory hormone and acute phase reactant, is proposed to contribute to the pathogenesis of atherosclerosis by promoting iron accumulation in plaque macrophages, leading to increased oxidative stress and inflammation in the plaque (the “iron hypothesis”). Hepcidin and iron may thus represent modifiable risk factors in atherosclerosis. We measured hepcidin expression in Apoe?/? mice with varying diets and ages. To assess the role of macrophage iron in atherosclerosis, we generated Apoe?/? mice with macrophage-specific iron accumulation by introducing the ferroportin ffe mutation. Macrophage iron loading was also enhanced by intravenous iron injection. Contrary to the iron hypothesis, we found that hepatic hepcidin expression was not increased at any stage of the atherosclerosis progression in Apoe?/? or Apoe/ffe mice and the atherosclerotic plaque size was not increased in mice with elevated macrophage iron. Our results strongly argue against any significant role of macrophage iron in atherosclerosis progression in mice. PMID:24316081

Kautz, Léon; Gabayan, Victoria; Wang, Xuping; Wu, Judy; Onwuzurike, James; Jung, Grace; Qiao, Bo; Lusis, Aldons J.; Ganz, Tomas; Nemeth, Elizabeta

2013-01-01

178

The cockerel as an animal model for atherosclerosis research.  

PubMed

The chicken is a good animal model for the study of atherosclerosis research because it is: 1. Omnivorous. 2. Small and suitable for prolonged laboratory investigation. 3. Able to develop spontaneous atherosclerosis. 4. Capable of producing atherosclerosis after cholesterol feeding with elevated hypercholesterolemia. A diet of 1/4% cholesterol plus 5% cottonseed oil added to starter-grower-mash resulted in aortic atherosclerosis with a slight but significant increase in plasma cholesterol. 5. Plasma levels of cholesterol and triglyceride are similar to those in humans. 6. Lipid composition of high and low density lipoproteins as well as chylomicrons resembles those of humans. 7. Has been noted that there is no essential difference between vascular lesions seen in chickens as a result of cholesterol diet and that of atherosclerosis observed in man. PMID:173152

Wong, H Y

1975-01-01

179

Quantum dot mediated imaging of atherosclerosis  

NASA Astrophysics Data System (ADS)

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.

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

2009-04-01

180

Mammographically Detectable Breast Arterial Calcification and Atherosclerosis  

PubMed Central

Breast arterial calcification (BAC), observed as an incidental finding on screening mammograms, represents degenerative calcific changes occurring in the mammary arteries, with increasing age. The aim of this review is to discuss relevant literature examining relation between BAC and atherosclerosis. After a thorough literature search, in OVID and PubMed, 199 studies were identified, of which 25 were relevant to our review. Data were abstracted from each study and statistical analysis was done, including calculation of odds ratios and construction of forest plots. A total of 35,542 patients were enrolled across 25 studies looking at an association between BAC and coronary artery disease, cardiovascular disease, stroke, cerebral artery disease, carotid and peripheral artery diseases, and coronary artery calcification. A majority of the studies showed a statistically significant relation between BAC and presence of coronary artery disease cardiovascular disease and associated mortality. Sensitivity of BAC in predicting cardiovascular events was low, but specificity was high. BAC was predictive of incident and prevalent stroke but not mortality of stroke. Similarly, BAC was predictive of cerebral, carotid, and peripheral artery diseases. The role of BAC as a surrogate marker of coronary and systemic atherosclerosis is currently uncertain. Its role may be further elucidated by more large-scale prospective studies and clinical experience. PMID:23584424

Shah, Neeraj; Chainani, Vinod; Delafontaine, Patrice; Abdo, Abir; Lafferty, James; Rafeh, Nidal Abi

2014-01-01

181

Vascular smooth muscle cell in atherosclerosis.  

PubMed

Vascular smooth muscle cells (VSMCs) exhibit phenotypic and functional plasticity in order to respond to vascular injury. In case of the vessel damage, VSMCs are able to switch from the quiescent 'contractile' phenotype to the 'proinflammatory' phenotype. This change is accompanied by decrease in expression of smooth muscle (SM)-specific markers responsible for SM contraction and production of proinflammatory mediators that modulate induction of proliferation and chemotaxis. Indeed, activated VSMCs could efficiently proliferate and migrate contributing to the vascular wall repair. However, in chronic inflammation that occurs in atherosclerosis, arterial VSMCs become aberrantly regulated and this leads to increased VSMC dedifferentiation and extracellular matrix formation in plaque areas. Proatherosclerotic switch in VSMC phenotype is a complex and multistep mechanism that may be induced by a variety of proinflammatory stimuli and hemodynamic alterations. Disturbances in hemodynamic forces could initiate the proinflammatory switch in VSMC phenotype even in pre-clinical stages of atherosclerosis. Proinflammatory signals play a crucial role in further dedifferentiation of VSMCs in affected vessels and propagation of pathological vascular remodelling. PMID:25677529

Chistiakov, D A; Orekhov, A N; Bobryshev, Y V

2015-05-01

182

Cardiac CT: atherosclerosis to acute coronary syndrome  

PubMed Central

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

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

2014-01-01

183

Mammographically detectable breast arterial calcification and atherosclerosis.  

PubMed

Breast arterial calcification (BAC), observed as an incidental finding on screening mammograms, represents degenerative calcific changes occurring in the mammary arteries, with increasing age. The aim of this review is to discuss relevant literature examining relation between BAC and atherosclerosis. After a thorough literature search, in OVID and PubMed, 199 studies were identified, of which 25 were relevant to our review. Data were abstracted from each study and statistical analysis was done, including calculation of odds ratios and construction of forest plots. A total of 35,542 patients were enrolled across 25 studies looking at an association between BAC and coronary artery disease, cardiovascular disease, stroke, cerebral artery disease, carotid and peripheral artery diseases, and coronary artery calcification. A majority of the studies showed a statistically significant relation between BAC and presence of coronary artery disease cardiovascular disease and associated mortality. Sensitivity of BAC in predicting cardiovascular events was low, but specificity was high. BAC was predictive of incident and prevalent stroke but not mortality of stroke. Similarly, BAC was predictive of cerebral, carotid, and peripheral artery diseases. The role of BAC as a surrogate marker of coronary and systemic atherosclerosis is currently uncertain. Its role may be further elucidated by more large-scale prospective studies and clinical experience. PMID:23584424

Shah, Neeraj; Chainani, Vinod; Delafontaine, Patrice; Abdo, Abir; Lafferty, James; Abi Rafeh, Nidal

2014-01-01

184

Endothelial activation. Sliding door to atherosclerosis.  

PubMed

The vascular endothelium has been long viewed as a simply physical separation between blood and tissue [1]. Over the last two decades a consistent bulk of data demonstrated that endothelium is a widely distributed organ, with a variable degree of heterogeneity among and within tissues [2, 3] and deeply involved in vascular physiology and pathophysiology, rather than a cellophane-like membrane that lines the circulatory system [1]. Being positioned at the interface of blood and tissue, the vascular endothelium is able to sense changes in hemodynamic forces and biochemical stimuli and promptly responds to local changes in biological needs by modulating vasomotion, hemostasis, angiogenesis, and vascular growth [1]. The vascular endothelium also modulates the trafficking of circulating blood cells by up-regulating adhesion molecules on cell surface [1, 4, 5]. These cell membrane-associated molecules are critic for leukocyte migration into specific organs under physiologic conditions and accelerate migration towards sites of inflammation [1, 4, 5]. Recently, the multi-step cascade of events that results in the local recruitment of leukocytes to sites of inflammatory challenge, also known as endothelial activation, has been considered as a crucial step in the initiation of atherosclerosis process, as well as in the development of advanced atherosclerosis [6]. PMID:16026286

Desideri, Giovambattista; Ferri, Claudio

2005-01-01

185

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

PubMed Central

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

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

186

Association of plasma lipid levels with atherosclerosis prevalence in psittaciformes.  

PubMed

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

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

2014-09-01

187

Age and Sex Differences in the Distribution and Ultrasound Morphology of Carotid Atherosclerosis The Tromsø Study  

Microsoft Academic Search

Atherosclerosis begins early in life and is the major underlying cause of cardiovascular morbidity and death. Yet, population-based information on age and sex differences in the extent and morphology of atherosclerosis throughout life is scarce. Carotid atherosclerosis can be visualized with B-mode ultrasound and is a marker of atherosclerosis elsewhere in the circulation. We assessed both the prevalence and the

Oddmund Joakimsen; Kaare H. Bønaa; Eva Stensland-Bugge; Bjarne Koster Jacobsen

188

Dendritic cell phenotypes of the central lymph in intact rabbits and during correction of experimental atherosclerosis  

Microsoft Academic Search

The investigation was conducted on 120 male chinchilla rabbits weighing 2-3.5 kg. The experimental animals as a whole were divided into groups: 1) intact; 2) animals with atherosclerosis; 3) animals with correction of atherosclerosis by radon; 4) animals with correction of atherosclerosis by polyphenol preparations obtained from Sanguisorba officinalis L.; 5) animals with atherosclerosis corrected by polyphenol preparations from S.

A. V. Kuznetsov

1992-01-01

189

Chemokines: established and novel targets in atherosclerosis  

PubMed Central

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

Koenen, Rory R; Weber, Christian

2011-01-01

190

Homocysteine and the pathogenesis of atherosclerosis.  

PubMed

The homocysteine theory of arteriosclerosis was discovered by study of arteriosclerotic plaques occurring in homocystinuria, a disease caused by deficiencies of cystathionine synthase, methionine synthase or methylenetetrahydrofolate reductase. According to the homocysteine theory, metabolic and nutritional abnormalities leading to elevation of plasma homocysteine cause atherosclerosis in the general population without these rare enzymatic abnormalities. Through studies of metabolism of homocysteine thiolactone, the anhydride of homocysteine, in cell cultures from homocystinuric children, the pathway for synthesis of sulfate was found to be dependent upon thioretinamide, the amide formed from retinoic acid and homocysteine thiolactone. Two molecules of thioretinamide form the complex thioretinaco with cobalamin, and oxidative phosphorylation is catalyzed by reduction of oxygen, which is bound to thioretinaco ozonide, by electrons from electron transport particles. Atherogenesis is attributed to formation of aggregates of homocysteinylated lipoproteins with microorganisms, which obstruct the vasa vasorum during formation of arterial vulnerable plaques. PMID:25653125

McCully, Kilmer S

2015-03-01

191

Methylglyoxal and glyoxalase I in atherosclerosis.  

PubMed

Cardiovascular disease, caused predominantly by atherosclerotic plaque rupture, remains one of the leading causes of death. However, the mechanism of plaque rupture remains largely unknown. Recent studies have linked high metabolic activity in inflamed atherosclerotic plaques to the development of plaque rupture. AGEs (advanced glycation end-products) are known to be formed as a result of high metabolic activity and are higher in rupture-prone than stable plaques. Furthermore, AGEs seem to be more than mere markers of metabolic activity, as recent studies have elucidated that AGEs and their major precursor, MG (methylglyoxal), may have an important role in the progression of atherosclerosis and plaque rupture. MG can be detoxified by Glo1 (glyoxalase I), thereby preventing the accumulation of MG and MG-derived AGEs. In the present review, data concerning MG, Glo1 and AGEs in the context of plaque phenotype are discussed. PMID:24646258

Hanssen, Nordin M J; Stehouwer, Coen D A; Schalkwijk, Casper G

2014-04-01

192

Atherosclerosis staging: imaging using FLIM technique  

NASA Astrophysics Data System (ADS)

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

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

2014-03-01

193

Effect of age on aortic atherosclerosis  

PubMed Central

Objective To examine the association of atherosclerosis burden in the survivors of an asymptomatic elderly cohort study and its relationship to other coronary risk factors (specifically, age) by evaluating aortic atherosclerotic wall burden by magnetic resonance imaging (MRI). Methods A total of 312 participants in an ongoing observational cohort study underwent cardiac and descending thoracic aorta imaging by MRI. Maximum wall thickness was measured and the mean wall thickness calculated. Wall/outer wall ratio was used as a normalized wall index (NWI) adjusted for artery size difference among participants. Percent wall volume (PWV) was calculated as NWI × 100. Results In this asymptomatic cohort (mean age: 76 years), the mean (SD) aortic wall area and wall thickness were 222 ± 45 mm2 and 2.7 ± 0.4 mm, respectively. Maximum wall thickness was 3.4 ± 0.6 mm, and PWV was 32% ± 4%. Women appeared to have smaller wall area, but after correcting for their smaller artery size, had significantly higher PWV than men (P = 0.03). Older age was associated with larger wall area (P = 0.04 for trend) with similar PWVs. However, there were no statistically significant associations between standard risk factors, Framingham global risk, or metabolic syndrome status, therapy for cholesterol or hypertension, coronary or aortic calcium score, and the aortic wall burden. Aortic calcification was associated with coronary calcification. Conclusions Asymptomatic elderly in this cohort had a greater descending thoracic aortic wall volume that correlated with age, and women had a significantly increased PWV compared to men. In these survivors, the atherosclerotic aortic wall burden was not significantly associated with traditional risk factors or with coronary or aortic calcium scores or coronary calcium progression. Results suggest that age, or as yet unidentified risk factor(s), may be responsible for the increase in atherosclerosis. PMID:23888172

Chen, Michael A.; Kawakubo, Miwa; Colletti, Patrick M.; Xu, Dongxiang; LaBree Dustin, Laurie; Detrano, Robert; Azen, Stanley P; Wong, Nathan D.; Zhao, Xue-Qiao

2013-01-01

194

Imaging Macrophage Development and Fate in Atherosclerosis and Myocardial Infarction  

PubMed Central

Macrophages are central regulators of disease progression in both atherosclerosis and myocardial infarction. In atherosclerosis, macrophages are the dominant leukocyte population that influences lesional development. In myocardial infarction, which is caused by atherosclerosis, macrophages accumulate readily and play important roles in inflammation and healing. Molecular imaging has grown considerably as a field and can reveal biological process at the molecular, cellular, and tissue levels. Here we explore how various imaging modalities, from intravital microscopy in mice to organ-level imaging in patients, are contributing to our understanding of macrophages and their progenitors in cardiovascular disease. PMID:23207281

Swirski, Filip K.; Nahrendorf, Matthias

2013-01-01

195

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

PubMed Central

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

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

2013-01-01

196

Chlamydiae and atherosclerosis: can psittacine cases support the link?  

PubMed

Atherosclerosis is a common disease in pet birds, particularly in psittacines. Little is known about the role of risk factors predisposing birds to this disease. In our study, we tried to detect chlamydiae in formalin-fixed and paraffin-embedded atherosclerotic tissue from 103 pet birds to clarify their role in atherosclerosis. Methods used were polymerase chain reaction (PCR), sequencing, and immunohistochemistry. Histopathologic examination served to classify the extent of atherosclerotic lesions. In the PCR, 4 (3.9%) of 103 cases, all of them with advanced stages of atherosclerosis, were positive. Subsequent sequence analysis revealed high identities (94%-100%) with Chlamydophila psittaci in three cases. Interestingly, two of these birds came from C. psittaci-infected populations. Because of the low incidence (3.9%), the occurrence only in advanced stages, and the association with C psittaci-infected avian populations, a causal relationship between chlamydiae and atherosclerosis in pet birds is rather improbable. PMID:17461260

Schenker, Olivier A; Hoop, Richard K

2007-03-01

197

Design of a bead holder for thermal atherosclerosis sensor  

E-print Network

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 ...

Savage, Christopher (Christopher R.)

2007-01-01

198

Atherosclerosis, Inflammation, Genetics, and Stem Cells: 2011 Update  

PubMed Central

Atherosclerosis is a peculiar form of inflammation triggered by cholesterol-rich lipoproteins and other noxious factors such as cigarette smoke, diabetes mellitus, and hypertension. Genetics also play an important role in the disease, accounting for about 40% of the risk. Of surprise in recent years of post-human genome sequencing, atherosclerosis-relevant genes discovered by non-biased techniques (ie, genome-wide association studies), did not rehash previously suspected pathways of lipid metabolism, diabetes, or hypertension. Instead these studies highlighted genes relevant to mechanisms of inflammation and stem cell biology. Only a minority of implicated genes were linked to lipid and other cardiac risk factor genes. Although such findings do not contradict the fact that atherosclerosis is triggered and exacerbated by elevated lipids, atherosclerosis “new genes” suggest that the mechanism responsible for the development of arterial lesions is more complex than a simple response to injury, where injury is necessary, but perhaps not sufficient, for disease progression. PMID:22476914

Goldschmidt-Clermont, Pascal J.; Dong, Chunming; Seo, David; Velazquez, Omaida

2012-01-01

199

Multi-Ethnic Study of Atherosclerosis (MESA) - Ancillary Eye Study  

ClinicalTrials.gov

Atherosclerosis; Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Cerebrovascular Disorders; Heart Failure, Congestive; Myocardial Infarction; Heart Diseases; Diabetes Mellitus, Non-insulin Dependent; Hypertension; Diabetic Retinopathy; Macular Degeneration; Diabetes Mellitus

2014-03-12

200

Cholesterol and hematopoietic stem cells: inflammatory mediators of atherosclerosis.  

PubMed

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

Lang, Jennifer K; Cimato, Thomas R

2014-05-01

201

Animal models for the atherosclerosis research: a review  

Microsoft Academic Search

Atherosclerosis is a leading cause of death worldwide, and its mechanisms are still unclear. However, various animal models\\u000a have significantly advanced our understanding of the mechanisms involved in atherosclerosis and have allowed the evaluation\\u000a of therapeutic options. The aim of this paper is to review those animal models (i.e., rabbits, mice, rats, guinea pigs, hamsters,\\u000a avian, carnivores, swine, and, non-human

Li Xiangdong; Liu Yuanwu; Zhang Hua; Ren Liming; Li Qiuyan; Li Ning

2011-01-01

202

Chemokines control mobilization, recruitment, and fate of monocytes in atherosclerosis.  

PubMed

Atherosclerosis is a chronic inflammatory disease of large arteries and, among others, characterized by continuous influx of monocytes into the subendothelial space, subsequent macrophage accumulation, and foam cell formation. Chemokines and their receptors tightly orchestrate monocyte trafficking and fate from birth to death. This brief review summarizes our current understanding of the interplay between monocytes and chemokines entertaining crucial processes in atherosclerosis development, progression, and regression. PMID:25792446

Drechsler, Maik; Duchene, Johan; Soehnlein, Oliver

2015-05-01

203

Proteomic profiling during atherosclerosis progression: Effect of nebivolol treatment  

Microsoft Academic Search

There is a great need for the identification of biomarkers for the early diagnosis of atherosclerosis and the agents to prevent\\u000a its progression. The aim of this study was to explore the effect of 24 week of nebivolol (a third-generation vasodilatory\\u000a beta-blocker) treatment on serum protein profiles in Apo E?\\/? mice during atherosclerosis progression. Nebivolol treated and non-treated (the control group)

Beste Ozben; Evrim Dursun; Emanuela Monari; Aurora Cuoghi; Stefania Bergamini; Aldo Tomasi; Tomris Ozben

2009-01-01

204

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

PubMed Central

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

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

2011-01-01

205

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

PubMed Central

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

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

206

Atherosclerosis and cardiovascular disease in the spondyloarthritides, particularly ankylosing spondylitis and psoriatic arthritis.  

PubMed

The spondyloarthritides (SpA) are a group of idiopathic inflammatory diseases affecting the axial and/or peripheral skeleton. Recent evidence points towards an increased mortality and morbidity due to cardiovascular disease, especially within the two major forms of SpA, ankylosing spondylitis and psoriatic arthritis. Several studies have identified alterations of the lipid profile, insulin sensitivity and other metabolic cardiovascular risk factors in SpA patients. An array of vascular morphologic and functional abnormalities has also been reported in these diseases, supporting the hypothesis of accelerated atherosclerosis in SpA. Inflammation appears to be a major player, involved both in the impairment of the classic cardiovascular risk factors, as well as directly in the process of endothelial injury, dysfunction and ultimately atherosclerosis. Multiple studies in rheumatoid arthritis have suggested that effective suppression of inflammation with synthetic disease-modifying anti-rheumatic drugs or with biologics may also exert favourable effects in the cardiovascular risk. Although such evidence is currently lacking for SpA, there is little doubt that physicians caring for patients with SpA should aim at controlling both inflammation and traditional cardiovascular risk factors. Such an integrated approach is expected to benefit patients in multiple levels. PMID:23406817

Papagoras, Charalampos; Voulgari, Paraskevi V; Drosos, Alexandros A

2013-01-01

207

Aortic Atherosclerosis in Systemic Lupus Erythematosus  

PubMed Central

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

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

2014-01-01

208

Atherosclerosis Susceptibility Loci Identified in an Extremely Atherosclerosis?Resistant Mouse Strain  

PubMed Central

Background C3H/HeJ (C3H) mice are extremely resistant to atherosclerosis, especially males. To understand the underlying genetic basis, we performed quantitative trait locus (QTL) analysis on a male F2 (the second generation from an intercross between 2 inbred strains) cohort derived from an intercross between C3H and C57BL/6 (B6) apolipoprotein E–deficient (Apoe?/?) mice. Methods and Results Two hundred forty?six male F2 mice were started on a Western diet at 8 weeks of age and kept on the diet for 5 weeks. Atherosclerotic lesions in the aortic root and fasting plasma lipid levels were measured. One hundred thirty?four microsatellite markers across the entire genome were genotyped. Four significant QTLs on chromosomes (Chr) 2, 4, 9, and 15 and 4 suggestive loci on Chr1, Chr4, and Chr7 were identified for atherosclerotic lesions. Unexpectedly, the C3H allele was associated with increased lesion formation for 2 of the 4 significant QTLs. Six loci for high?density lipoprotein (HDL), 6 for non?HDL cholesterol, and 3 for triglycerides were also identified. The QTL for atherosclerosis on Chr9 replicated Ath29, originally mapped in a female F2 cohort derived from B6 and C3H Apoe?/? mice. This locus coincided with a QTL for HDL, and there was a moderate, but statistically significant, correlation between atherosclerotic lesion sizes and plasma HDL cholesterol levels in F2 mice. Conclusions These data indicate that most atherosclerosis susceptibility loci are distinct from those for plasma lipids except for the Chr9 locus, which exerts effect through interactions with HDL. PMID:23938286

Rowlan, Jessica S.; Li, Qiongzhen; Manichaikul, Ani; Wang, Qian; Matsumoto, Alan H.; Shi, Weibin

2013-01-01

209

Niemann-Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking  

PubMed Central

Niemann-Pick C1 (NPC1) is a key participant in cellular cholesterol trafficking. Loss of NPC1 function leads to defective suppression of SREBP-dependent gene expression and failure to appropriately activate liver X receptor–mediated (LXR-mediated) pathways, ultimately resulting in intracellular cholesterol accumulation. To determine whether NPC1 contributes to regulation of macrophage sterol homeostasis in vivo, we examined the effect of NPC1 deletion in BM-derived cells on atherosclerotic lesion development in the Ldlr–/– mouse model of atherosclerosis. High-fat diet–fed chimeric Npc1–/– mice reconstituted with Ldlr–/–Npc1–/– macrophages exhibited accelerated atherosclerosis despite lower serum cholesterol compared with mice reconstituted with wild-type macrophages. The discordance between the low serum lipoprotein levels and the presence of aortic atherosclerosis suggested that intrinsic alterations in macrophage sterol metabolism in the chimeric Npc1–/– mice played a greater role in atherosclerotic lesion formation than did serum lipoprotein levels. Macrophages from chimeric Npc1–/– mice showed decreased synthesis of 27-hydroxycholesterol (27-HC), an endogenous LXR ligand; decreased expression of LXR-regulated cholesterol transporters; and impaired cholesterol efflux. Lower 27-HC levels were associated with elevated cholesterol oxidation products in macrophages and plasma of chimeric Npc1–/– mice and with increased oxidative stress. Our results demonstrate that NPC1 serves an atheroprotective role in mice through regulation of LXR-dependent cholesterol efflux and mitigation of cholesterol-induced oxidative stress in macrophages. PMID:18483620

Zhang, Jessie R.; Coleman, Trey; Langmade, S. Joshua; Scherrer, David E.; Lane, Lindsay; Lanier, M. Hunter; Feng, Chu; Sands, Mark S.; Schaffer, Jean E.; Semenkovich, Clay F.; Ory, Daniel S.

2008-01-01

210

Molecular Imaging of Inflammation in Atherosclerosis  

PubMed Central

Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

2013-01-01

211

Genomic correlates of atherosclerosis in ancient humans.  

PubMed

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

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

2014-06-01

212

Atherosclerosis: from biology to pharmacological treatment  

PubMed Central

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

Riccioni, Graziano; Sblendorio, Valeriana

2012-01-01

213

Endothelium Preserving Microwave Treatment for Atherosclerosis  

NASA Technical Reports Server (NTRS)

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.

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

214

Endothelium Preserving Microwave Treatment for Atherosclerosis  

NASA Technical Reports Server (NTRS)

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.

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

215

3-Nitrotyrosine Modified Proteins in Atherosclerosis  

PubMed Central

Cardiovascular disease is the leading cause of premature death worldwide, and atherosclerosis is the main contributor. Lipid-laden macrophages, known as foam cells, accumulate in the subendothelial space of the lesion area and contribute to consolidate a chronic inflammatory environment where oxygen and nitrogen derived oxidants are released. Oxidatively modified lipids and proteins are present both in plasma as well as atherosclerotic lesions. A relevant oxidative posttranslational protein modification is the addition of a nitro group to the hydroxyphenyl ring of tyrosine residues, mediated by nitric oxide derived oxidants. Nitrotyrosine modified proteins were found in the lesion and also in plasma from atherosclerotic patients. Despite the fact of the low yield of nitration, immunogenic, proatherogenic, and prothrombotic properties acquired by 3-nitrotyrosine modified proteins are in agreement with epidemiological studies showing a significant correlation between the level of nitration found in plasma proteins and the prevalence of cardiovascular disease, supporting the usefulness of this biomarker to predict the outcome and to take appropriate therapeutic decisions in atherosclerotic disease.

2015-01-01

216

Endothelium Preserving Microwave Treatment for Atherosclerosis  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

217

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

PubMed

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 (AT?Rs), 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 AT?R 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 AT?R. 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 AT?R, 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

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

2015-01-01

218

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

PubMed Central

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

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

2015-01-01

219

Immune Mechanisms in Atherosclerosis, Especially in Diabetes Type 2  

PubMed Central

Atherosclerosis and ensuing cardiovascular disease (CVD) are major complications of diabetes type 2. Atherosclerosis is a chronic inflammatory condition involving immunocompetent cells of different types present in the lesions. Even though inflammation and immune activation may be more pronounced in atherosclerosis in diabetes type 2, there does not appear to be any major differences between diabetics and non-diabetics. Similar factors are thus implicated in atherosclerosis-associated immune activation in both groups. The cause of immune activation is not known and different mutually non-exclusive possibilities exist. Oxidized and/or enzymatically modified forms of low-density lipoprotein (OxLDL) and dead cells are present in atherosclerotic plaques. OxLDL could play a role, being pro-inflammatory and immunostimulatory as it activates T-cells and is cytotoxic at higher concentrations. Inflammatory phospholipids in OxLDL are implicated, with phosphorylcholine (PC) as one of the exposed antigens. Antibodies against PC (anti-PC) are anti-atherogenic in mouse studies, and anti-PC is negatively associated with development of atherosclerosis and CVD in humans. Bacteria and virus have been discussed as potential causes of immune activation, but it has been difficult to find direct evidence supporting this hypothesis, and antibiotic trials in humans have been negative or inconclusive. Heat shock proteins (HSP) could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include cytokines such as interleukin 1? (IL-1?), tumor necrosis factor (TNF), and also lipid mediators as leukotrienes. In addition, in diabetes, hyperglycemia and oxidative stress appear to accelerate the development of atherosclerosis, one mechanism could be via promotion of immune reactions. To prove that immune reactions are causative of atherosclerosis and CVD, further studies with immune-modulatory treatments are needed. PMID:24194733

Frostegård, Johan

2013-01-01

220

Coronary atherosclerosis in noncardiac deaths: An autopsy study  

PubMed Central

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.

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

2015-01-01

221

Infection-associated biomarkers of inflammation in atherosclerosis.  

PubMed

Atherosclerosis is a systemic inflammatory disease leading to lipid-laden inflammatory lesions in the arterial walls that may destabilize and rupture. It is becoming clear that addressing the "classical" risk factors for atherosclerosis does not entirely reduce the risk of cardiovascular events. Novel biomarkers to be used in highthroughput assays are necessary for diagnosis, for determination of the residual risk and for monitoring the effects of the therapy. Since inflammation is a hallmark of atherosclerosis, tests for pro-inflammatory biomarkers have been introduced such as for hsCRP, fibrinogen and IL-6, with many more at different stages of development. There has been a dearth of novel approaches for the diagnosis and management of atherosclerosis, reflected in a continuous reliance on LDL cholesterol as a proven target of investigations. To bring another perspective, here we briefly overview the accumulated epidemiological and sero-epidemiological evidence suggesting systemic infections as a component of atherosclerotic inflammations. We have shown that different individuals' plaques are colonized with different bacterial species (atherosclerosis microbiota). Most of the time the pathogens are likely in an intracellular state, shielded from the host immune responses. There are controlled clinical trials and metaanalyses that corroborate the infections, specifically periodontal disease as a contributing risk factor of atherosclerosis. Infection-related markers, including transcriptome signatures, may identify latent infection patients with sub-clinical disease. Thus, the emerging infection- associated markers of inflammation could complement the existing ones and their use as companion diagnostics for atherosclerosis should stimulate the growing field of personalized medicine within cardiovascular diseases. PMID:25435361

Kozarov, Emil; Huber, Kurt; Wojta, Johann

2015-01-01

222

IL-1 and atherosclerosis: a murine twist to an evolving human story  

PubMed Central

Inflammation is a critical component of atherosclerosis. IL-1 is a classic proinflammatory cytokine that has been linked to atherosclerosis. A clinical trial has been launched in which an antibody specific for IL-1? is being studied for its effects on cardiovascular events in patients with atherosclerosis. In this issue of the JCI, Alexander et al. report that mice lacking the receptor for IL-1 unexpectedly have features of advanced atherosclerosis that suggest the atherosclerotic plaques may be less stable. These findings illustrate the complexity of inflammatory pathways in atherosclerosis and suggest the need for careful calibration of antiinflammatory approaches to atherosclerosis. PMID:22201674

Rader, Daniel J.

2011-01-01

223

IL-1 and atherosclerosis: a murine twist to an evolving human story.  

PubMed

Inflammation is a critical component of atherosclerosis. IL-1 is a classic proinflammatory cytokine that has been linked to atherosclerosis. A clinical trial has been launched in which an antibody specific for IL-1? is being studied for its effects on cardiovascular events in patients with atherosclerosis. In this issue of the JCI, Alexander et al. report that mice lacking the receptor for IL-1 unexpectedly have features of advanced atherosclerosis that suggest the atherosclerotic plaques may be less stable. These findings illustrate the complexity of inflammatory pathways in atherosclerosis and suggest the need for careful calibration of antiinflammatory approaches to atherosclerosis. PMID:22201674

Rader, Daniel J

2012-01-01

224

A multiscale approach for modeling atherosclerosis progression.  

PubMed

Progression of atherosclerotic process constitutes a serious and quite common condition due to accumulation of fatty materials in the arterial wall, consequently posing serious cardiovascular complications. In this paper, we assemble and analyze a multitude of heterogeneous data in order to model the progression of atherosclerosis (ATS) in coronary vessels. The patient's medical record, biochemical analytes, monocyte information, adhesion molecules, and therapy-related data comprise the input for the subsequent analysis. As indicator of coronary lesion progression, two consecutive coronary computed tomography angiographies have been evaluated in the same patient. To this end, a set of 39 patients is studied using a twofold approach, namely, baseline analysis and temporal analysis. The former approach employs baseline information in order to predict the future state of the patient (in terms of progression of ATS). The latter is based on an approach encompassing dynamic Bayesian networks whereby snapshots of the patient's status over the follow-up are analyzed in order to model the evolvement of ATS, taking into account the temporal dimension of the disease. The quantitative assessment of our work has resulted in 93.3% accuracy for the case of baseline analysis, and 83% overall accuracy for the temporal analysis, in terms of modeling and predicting the evolvement of ATS. It should be noted that the application of the SMOTE algorithm for handling class imbalance and the subsequent evaluation procedure might have introduced an overestimation of the performance metrics, due to the employment of synthesized instances. The most prominent features found to play a substantial role in the progression of the disease are: diabetes, cholesterol and cholesterol/HDL. Among novel markers, the CD11b marker of leukocyte integrin complex is associated with coronary plaque progression. PMID:24835229

Exarchos, Konstantinos P; Carpegianni, Clara; Rigas, Georgios; Exarchos, Themis P; Vozzi, Federico; Sakellarios, Antonis; Marraccini, Paolo; Naka, Katerina; Michalis, Lambros; Parodi, Oberdan; Fotiadis, Dimitrios I

2015-03-01

225

Accelerated atherosclerosis in patients with SLE--mechanisms and management.  

PubMed

Rapid-onset cardiovascular disease (CVD) is a major concern for many patients with systemic lupus erythematosus (SLE). Cardiovascular events occur more frequently and with earlier onset in patients with SLE compared with healthy individuals. Traditional risk factors, such as altered lipid levels, aging and smoking, do not fully explain this increased risk of CVD, strongly suggesting that autoimmunity contributes to accelerated atherosclerosis. Altered immune system function is recognized as the primary contributor to both the initiation and progression of atherosclerosis. Multiple manifestations of autoimmunity, including changes in cytokine levels and innate immune responses, autoantibodies, adipokines, dysfunctional lipids, and oxidative stress, could heighten atherosclerotic risk. In addition, multiple SLE therapeutics seem to affect the development and progression of atherosclerosis both positively and negatively. SLE-specific cardiovascular risk factors are beginning to be discovered by several groups, and development of a comprehensive, clinically feasible biomarker panel could be invaluable for identification and treatment of patients at risk of developing accelerated atherosclerosis. Here, we discuss the epidemiology of CVD in SLE and the implications of immune system dysfunction on the development and progression, monitoring and treatment of atherosclerosis in individuals with this disease. PMID:22331061

Skaggs, Brian J; Hahn, Bevra H; McMahon, Maureen

2012-04-01

226

G Protein-coupled Estrogen Receptor Protects from Atherosclerosis  

PubMed Central

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

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

227

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

PubMed

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

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

228

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

E-print Network

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

Paris-Sud XI, Université de

229

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 ...

230

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

Federal Register 2010, 2011, 2012, 2013, 2014

...of Atherosclerosis (MESA) Event Surveillance SUMMARY: In compliance...submitted to the Office of Management and Budget (OMB) for review...of Atherosclerosis (MESA) Event Surveillance. Type of Information...information about clinical CVD events that participants...

2010-08-04

231

Applications of miRNA Technology for Atherosclerosis  

PubMed Central

MicroRNAs (miRNAs) are a class of post-transcriptional regulators that provide a mechanism of gene silencing by translational repression or degradation of the targeted gene. Gene expression regulation by miRNAs is involved in most if not all physiological and pathophysiological processes. Atherosclerosis is a major cardiovascular disease pathology regulated by miRNAs. Recent miRNA profiling studies have implicated the potential use of miRNAs as biomarkers in patients with atherosclerosis, as both diagnostic and prognostic indicators. This review will discuss the clinical and basic science research information that has been gleaned regarding miRNA roles in dyslipidemia, diabetes, obesity, and insulin resistance which are the major stimulators for the development of atherosclerosis. PMID:24395388

Toba, Hiroe; Lindsey, Merry L.; Chilton, Robert J.

2015-01-01

232

Role of Helicobacter pylori infection in pathogenesis of atherosclerosis.  

PubMed

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

Vijayvergiya, Rajesh; Vadivelu, Ramalingam

2015-03-26

233

Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis  

SciTech Connect

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

Qiao, Wang [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)] [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China); Chaoshu, Tang [Department of Physiology and Pathophysiology, Health Sciences Center, Peking University, Beijing 100034 (China) [Department of Physiology and Pathophysiology, Health Sciences Center, Peking University, Beijing 100034 (China); Key Laboratory of Molecular Cardiovascular Medicine, Ministry of Education (China); Hongfang, Jin, E-mail: jinhongfang51@126.com [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)] [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China); Junbao, Du, E-mail: junbaodu1@126.com [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)] [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)

2010-05-28

234

Redox balance and blood elemental levels in atherosclerosis  

NASA Astrophysics Data System (ADS)

Oxidation of lipids and proteins represents a causative event for atherogenesis, which can be opposed by antioxidant activity. Elements, such as, Fe, Cu, Zn and Se can be involved in both mechanisms. Thus, evaluation of blood elemental levels, easily detected by PIXE, and of redox parameters may be useful in assessing the risk of atherosclerosis. A group of stable patients suffering from atherosclerosis, was matched with a cohort of normo-tensive and -lipidemic volunteers. Although no major discrepancies were observed for trace elemental levels in blood, increased concentrations of K and Ca were found in atherosclerotic group. Patients presented enhance levels of antioxidant (?-tocopherol) and decreased of protein oxidation (protein carbonyls), while for the lipid oxidation marker (malondialdehyde) no variation was observed. This study contributes to a better understanding of atherosclerosis development and its relationship with blood elemental levels, and set basis for further clinical trials with pathological groups in acute phase.

Napoleão, P.; Lopes, P. A.; Santos, M.; Steghens, J.-P.; Viegas-Crespo, A. M.; Pinheiro, T.

2006-08-01

235

Dendritic cells in atherosclerosis: evidence in mice and humans.  

PubMed

Atherosclerotic vascular disease is driven by chronic inflammation involving both innate and adaptive immune responses. Dendritic cells (DCs) are found in healthy arteries and accumulate in atherosclerotic lesions and engage in diverse pathogenic and protective mechanisms during atherogenesis. DCs contribute to early foam cell formation, regulate lipid metabolism, and control pro- and antiatherosclerotic T-cell responses by multifarious mechanisms. We, here, review the roles of DCs and plasmacytoid DCs in experimental models of atherosclerosis and the approaches to target DCs in therapeutic vaccination strategies. We, furthermore, discuss the evidence of the potential function of DCs in human atherosclerosis, and dissect the efforts to harness DC subsets as biomarkers of disease. Finally, we discuss necessary future steps that will help to understand the specific contribution of bona fide DCs in atherosclerosis to move toward novel therapeutic approaches. PMID:25675999

Zernecke, Alma

2015-04-01

236

Role of Helicobacter pylori infection in pathogenesis of atherosclerosis  

PubMed Central

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

Vijayvergiya, Rajesh; Vadivelu, Ramalingam

2015-01-01

237

MAOA Genotype, Childhood Trauma and Subclinical Atherosclerosis: A Twin Study  

PubMed Central

Objective A functional promoter polymorphism in the MAOA gene has been implicated in neuropsychiatric disorders and also moderates the association between early life stress and mental disorders, which often co-occur with cardiovascular disease. No study has examined the relationship between MAOA genotype, childhood trauma and subclinical atherosclerosis. The objective of this investigation was to examine whether childhood trauma moderates the association between MAOA genotype and subclinical atherosclerosis. Methods A sample including 289 middle-aged male twin pairs was studied. Subclinical atherosclerosis was assessed by brachial flow-mediated dilation (FMD) using ultrasound. Childhood trauma, before age 18, was measured with the Early Trauma Inventory and included physical, emotional, and sexual abuse as well as general trauma. Generalized estimating equation models were used to test the main and interactive effects of the MAOA genotype and each domain of childhood trauma on FMD, adjusting for known risk factors. Results General trauma was the most prevalent childhood trauma (28.4%), followed by physical abuse (25.0%), emotional abuse (19.4%) and sexual abuse (11.6%). MAOA genotype was not associated with any domain of childhood trauma (? ? 0.36). There was no significant evidence for a main effect for the MAOA genotype (? = 0.02, p = 0.82) or childhood trauma (0.005 < ? < 0.10, p > 0.54) on early atherosclerosis. However, a significant interaction was observed between MAOA genotype and physical (?interaction = 0.37, p = 0.026) or emotional abuse (?interaction = 0.43, p = 0.025) on subclinical atherosclerosis. Conclusion This study provides initial evidence that childhood trauma modulates the impact of MAOA variant on subclinical atherosclerosis, independent of traditional cardiovascular risk factors. PMID:23723362

Zhao, Jinying; Bremner, James D.; Goldberg, Jack; Quyyumi, Arshed A.; Vaccarino, Viola

2013-01-01

238

Human Genetic Evidence for Involvement of CD137 in Atherosclerosis  

PubMed Central

Atherosclerosis is an inflammatory disease and the main cause of cardiovascular disease. Inflammation promotes plaque instability and clinical disease, such as myocardial infarction, stroke and peripheral vascular disease. Subclinical atherosclerosis begins with thickening of the arterial intimal layer, and increased intima-media thickness (IMT) in the carotid artery is a widely used measurement of subclinical atherosclerosis. Activation of CD137 (tumor necrosis factor receptor super family 9) promotes inflammation and disease development in murine atherosclerosis. CD137 is expressed in human atherosclerosis, but its role is largely unknown. This study uses a genetic approach to investigate CD137 in human atherosclerotic disease. In publicly available data on genotype and gene expression from the HapMap project, the minor T allele of rs2453021, a single nucleotide polymorphism in CD137, was significantly associated with CD137 gene expression. In the PROCARDIS and Wellcome Trust Case Control Consortium (WTCCC) cohorts of 13,029 cases and controls, no significant association was detected between the minor T allele of rs2453021 and risk for coronary artery disease or myocardial infarction. However, in the IMPROVE multicenter study of 3,418 individuals, the minor T allele of rs2453021 was associated with increased IMT of the common carotid artery (CCA), as measured by ultrasonography, with presence of plaque in CCA and with increased incidence of adverse noncardiac vascular events. Taken together, this study shows that the minor T allele of rs2453021 is associated with increased IMT in the CCA and increased risk of incident noncardiac vascular events, thus providing the first human genetic evidence for involvement of CD137 in atherosclerosis. PMID:25032953

Söderström, Leif Å; Gertow, Karl; Folkersen, Lasse; Sabater-Lleal, Maria; Sundman, Eva; Sheikine, Yuri; Goel, Anuj; Baldassarre, Damiano; Humphries, Steve E; de Faire, Ulf; Watkins, Hugh; Tremoli, Elena; Veglia, Fabrizio; Hamsten, Anders; Hansson, Göran K; Olofsson, Peder S

2014-01-01

239

Lipid Rafts and Redox Regulation of Cellular Signaling in Cholesterol Induced Atherosclerosis  

PubMed Central

Redox mediated signaling mechanisms play crucial roles in the pathogenesis of several cardiovascular diseases. Atherosclerosis is one of the most important disorders induced mainly by hypercholesterolemia. Oxidation products and related signaling mechanisms are found within the characteristic biomarkers of atherosclerosis. Several studies have shown that redox signaling via lipid rafts play a significant role in the regulation of pathogenesis of many diseases including atherosclerosis. This review attempts to summarize redox signaling and lipid rafts in hypercholesterolemia induced atherosclerosis. PMID:22043207

Catalgol, Betul; Kartal Ozer, Nesrin

2010-01-01

240

Anti-inflammatory therapeutics for the treatment of atherosclerosis  

PubMed Central

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

Charo, Israel F.; Taub, Rebecca

2013-01-01

241

Anti-inflammatory therapeutics for the treatment of atherosclerosis.  

PubMed

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

Charo, Israel F; Taub, Rebecca

2011-05-01

242

The Influence of Innate and Adaptive Immune Responses on Atherosclerosis  

PubMed Central

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

Witztum, Joseph L.; Lichtman, Andrew H.

2014-01-01

243

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

Microsoft Academic Search

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

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

1994-01-01

244

Accelerated Atherosclerosis and Calcification in Vein Grafts: A Study in APOE*3 Leiden Transgenic Mice  

Microsoft Academic Search

Vein grafts fail due to development of intimal hyperplasia and accelerated atherosclerosis. Many murine genetic models in which genes are overexpressed, deleted, or mutated have been introduced recently. Therefore, mouse models are very well suited to dissect the relative contribution of different genes in the development of accelerated atherosclerosis. In the present study, we evaluated whether accelerated atherosclerosis in human

J. H. P. Lardenoye; M. R. de Vries; Q. Xu; C. R. Dhore; J. P. M. Cleutjens; V. W. M. van Hinsbergh; J. H. van Bockel; P. H. A. Quax

2002-01-01

245

IRF5 Deficiency Ameliorates Lupus but Promotes Atherosclerosis and Metabolic Dysfunction in a Mouse Model of Lupus-Associated Atherosclerosis.  

PubMed

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

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

246

Evaluation of the biomechanics of atherosclerosis by acoustic microscopy  

NASA Astrophysics Data System (ADS)

Acoustic microscopy provides not only the morphology, but also the biomechanical properties of the biological soft tissues. The biomechanics of atherosclerosis is important because the pathophysiology of atherosclerosis is closely related with mechanical properties and mechanical stress. Rupture of the fibrous cap of atheromatous plaque is the initial event in acute coronary syndrome such as acute myocardial infarction or unstable angina. In addition to extrinsic physical stresses to the plaque, the intrinsic biomechanical property of the plaque is important for assessing the mechanism of the rupture. Two sets of SAMs operating in 100 to 200 MHz and in 800 MHz to 1.3 GHz were equipped to measure the acoustic properties of atherosclerosis of human or mouse arteries. The values of attenuation and sound speed in the tissue components of atherosclerosis were measured by analyzing the frequency dependent characteristics of the amplitude and phase signals. Both values were highest in calcification and lowest in lipid pool. Although attenuation and sound speed were relatively high in intimal fibrosis, the inhomogeneity of acoustic parameters was found within the fibrous cap. Polarized microscopy for the collagen stained with Picrosirius red showed that the attenuation of ultrasound was significantly higher in type I collagen with orange polarized color compared to type III collagen with green color. SAM has shown the possibility to detect the plaque vulnerability and it might improve our understanding of the sudden rupture from micro-mechanical point of view.

Saijo, Yoshifumi; Nitta, Shin-ichi; Schiott Jorgensen, Claus; Falk, Erling

2001-07-01

247

The Role of Oxidative Stress and Autophagy in Atherosclerosis  

PubMed Central

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

Perrotta, Ida; Aquila, Saveria

2015-01-01

248

Association of carotid atherosclerosis and left ventricular hypertrophy  

Microsoft Academic Search

Objectives. This study was undertaken to determine the prevalence of carotid atherosclerosis in a large group of asymptomatic hypertensive and normotensive adults and to examine its relation to the presence of left ventricular hypertrophy.Background. Both electrocardiographic and echocardiographic left ventricular hypertrophy predict an increased risk of cardiovascular events and mortality, including cerebrovascular disease, but the mechanism of association is unknown.Methods.

Mary J Roman; Thomas G Pickering; Joseph E Schwartz; Riccardo Pini; Richard B Devereux

1995-01-01

249

Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development.  

PubMed

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

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

250

Cell signaling by reactive nitrogen and oxygen species in atherosclerosis  

NASA Technical Reports Server (NTRS)

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.

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

2000-01-01

251

A role of matrix metalloproteinase-8 in atherosclerosis  

PubMed Central

Rationale Atherosclerotic lesions express matrix metalloproteinase-8 (MMP8) which possesses proteolytic activity on matrix proteins particularly fibrillar collagens and on non-matrix proteins such as angiotensin I (Ang I). Objective We studied whether MMP8 plays a role in atherogenesis. Methods and Results In atherosclerosis-prone apoE deficient mice, inactivating MMP8 resulted in a substantial reduction in atherosclerotic lesion formation. Immunohistochemical examinations showed that atherosclerotic lesions in MMP8 deficient mice had significantly fewer macrophages but increased collagen content. In line with results of in vitro assays showing Ang I cleavage by MMP8 generating angiotensin II (Ang II), MMP8 knockout mice had lower Ang II levels and lower blood pressure. In addition, we found that products of Ang I cleavage by MMP8 increased vascular cell adhesion molecule-1 (VCAM-1) expression and that MMP8 deficient mice had reduced VCAM-1 expression in atherosclerotic lesions. Intravital microscopy analysis showed that leukocyte rolling and adhesion on vascular endothelium was reduced in MMP8 knockout mice. Furthermore, we detected an association between MMP8 gene variation and extent of coronary atherosclerosis in patients with coronary artery disease. A relationship between MMP8 gene variation, plasma VCAM-1 level and atherosclerosis progression was also observed in a population-based, prospective study. Conclusion These results indicate that MMP8 is an important player in atherosclerosis. PMID:19745165

Laxton, Ross C.; Hu, Yanhua; Duchene, Johan; Zhang, Feng; Zhang, Zhongyi; Leung, Kit-Yi; Xiao, Qingzhong; Scotland, Ramona S.; Hodgkinson, Conrad P.; Smith, Katherine; Willeit, Johann; López-Otín, Carlos; Simpson, Iain A.; Kiechl, Stefan; Ahluwalia, Amrita; Xu, Qingbo; Ye, Shu

2010-01-01

252

Atherosclerosis in chronic kidney disease: the role of macrophages  

Microsoft Academic Search

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

Valentina Kon; MacRae F. Linton; Sergio Fazio

2010-01-01

253

Anti-inflammatory therapeutics for the treatment of atherosclerosis  

Microsoft Academic Search

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

Israel F. Charo; Rebecca Taub

2011-01-01

254

Obstructive Sleep Apnea, Immuno-Inflammation and Atherosclerosis  

E-print Network

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

Paris-Sud XI, Université de

255

Corticosterone accelerates atherosclerosis in the apolipoprotein E-deficient mouse.  

PubMed

Chronic stress is an important risk factor for atherosclerosis, which is a chief process in the development of cardiovascular disease. Increased circulating levels of corticosterone have been documented in several animal models of chronic stress. However, it remains to be established whether corticosterone is sufficient to exacerbate atherosclerosis. To test this hypothesis, apolipoprotein E (ApoE)-deficient mice were fed a high-fat diet for 13 weeks with exposure to either corticosterone or vehicle in the drinking water (CORT and Con). Corticosterone treatment significantly increased atherosclerotic plaque area at the aortic root. Such exacerbation of atherosclerosis was accompanied by significantly lower levels of circulating white blood cells and serum interleukin-1? (IL-1?), and significantly elevated serum concentrations of total cholesterol, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and small dense low-density lipoprotein (sd-LDL) in CORT mice when compared to Con mice. These findings demonstrate that corticosterone is sufficient to exacerbate atherosclerosis in vivo despite its anti-inflammatory properties and that this marked pro-atherogenic phenotype is primarily associated with increased dyslipidaemia. PMID:24468157

Okutsu, Mitsuharu; Lira, Vitor A; Higashida, Kazuhiko; Peake, Jonathan; Higuchi, Mitsuru; Suzuki, Katsuhiko

2014-02-01

256

Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development  

PubMed Central

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

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

257

Gasoline Exhaust Emissions Induce Vascular Remodeling Pathways Involved in Atherosclerosis  

Microsoft Academic Search

Epidemiological evidence indicates that environmental air pollutants are positively associated with the development of chronic vascular disease; however, the mechanisms involved have not been fully elucidated. In the present study we examined molecular pathways associated with chronic vascular disease in atherosclerosis-prone apolipoprotein E-deficient (ApoE? \\/? ) mice, including markers of vascular remodeling and oxidative stress, in response to exposure to

Amie K. Lund; Travis L. Knuckles; Chrys Obot Akata; Ralph Shohet; Jacob D. McDonald; Andrew Gigliotti; Jean Clare Seagrave; Matthew J. Campen

2007-01-01

258

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

PubMed

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

Peng, Kuang; Liu, Lushan; Wei, Dangheng; Lv, Yuncheng; Wang, Gang; Xiong, Wenhao; Wang, Xiaoqing; Altaf, Afrasyab; Wang, Lili; He, Dan; Wang, Hongyan; Qu, Peng

2015-05-01

259

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

SciTech Connect

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

Wang, Yi-Xiang J., E-mail: yi-xiang.wang@astrazeneca.com; Kuribayashi, Hideto [AstraZeneca (United Kingdom); Wagberg, Maria [AstraZeneca (Sweden); Holmes, Andrew P.; Tessier, Jean J.; Waterton, John C. [AstraZeneca (United Kingdom)

2006-08-15

260

Subclinical Atherosclerosis and Obesity Phenotypes Among Mexican Americans  

PubMed Central

Background Data on the influence of obesity on atherosclerosis in Hispanics are inconsistent, possibly related to varying cardiometabolic risk among obese individuals. We aimed to determine the association of obesity and cardiometabolic risk with subclinical atherosclerosis in Mexican?Americans. Methods and Results Participants (n=503) were drawn from the Cameron County Hispanic Cohort. Metabolic health was defined as <2 of the following: blood pressure ?130/85; triglyceride ?150 mg/dL; high?density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women); fasting glucose ?100 mg/dL; homeostasis model assessment of insulin resistance value >5.13; or high?sensitivity C?reactive protein >3 mg/L. Carotid intima media thickness (cIMT) was measured. A high proportion of participants (77.8%) were metabolically unhealthy; they were more likely to be male, older, with fewer years of education, and less likely to meet daily recommendations regarding fruit and vegetable servings. One?third (31.8%) had abnormal carotid ultrasound findings. After adjusting for covariates, mean cIMT varied across the obesity phenotypes (P=0.0001); there was no difference among the metabolically unhealthy regardless of whether they were obese or not. In multivariable analysis, after adjusting for covariates, cardiometabolic risk (P=0.0159), but not obesity (P=0.1446), was significantly associated with subclinical atherosclerosis. Conclusions In Mexican?Americans, cardiometabolic risk has a greater effect on early atherosclerosis development than body mass index. Non?obese but metabolically unhealthy participants had similar development of subclinical atherosclerosis as their obese counterparts. Interventions to maintain metabolic health among obese and non?obese patients may be a more important goal than weight loss alone. PMID:25787312

Laing, Susan T.; Smulevitz, Beverly; Vatcheva, Kristina P.; Rahbar, Mohammad H.; Reininger, Belinda; McPherson, David D.; McCormick, Joseph B.; Fisher?Hoch, Susan P.

2015-01-01

261

Socioeconomic differences in the progression of carotid atherosclerosis in middle-aged men and women with subclinical atherosclerosis in Sweden  

Microsoft Academic Search

While the persistence of socioeconomic differences in cardiovascular disease (CVD) has been recognized for many years, less is known about whether socioeconomic factors are of importance to CVD before symptoms of the disease appear. In this study the associations among educational level, occupational status and progression of atherosclerosis were investigated in 1016 Swedish middle-aged men and women with signs of

Maria Rosvall; Per-Olof Östergren; Bo Hedblad; Sven-Olof Isacsson; Lars Janzon; Göran Berglund

2006-01-01

262

Atherosclerosis-susceptible and atherosclerosis-resistant pigeon aortic cells express different genes in vivo.  

PubMed

Spontaneous atherosclerosis in the White Carneau (WC-As) pigeon is inherited as a single gene disorder, and its progression closely mirrors the human disease. Representational difference analysis and microarray were used to identify genes that were differentially expressed between the susceptible WC-As and resistant Show Racer (SR-Ar) aortic tissue. The RNA extracted from 1-d-old squab aortas was used to make cDNA for each experiment. Fifty-six unique genes were found using representational difference analysis, with 25 exclusively expressed in the WC-As, 15 exclusive to the SR-Ar, and 16 nonexclusive genes having copy number variation between breeds. Caveolin and ?-actin were expressed in the WC-As, whereas the proteasome maturation protein and the transcription complex CCR4-NOT were exclusive to the SR-Ar. Microarray analysis revealed 48 genes with differential expression. Vascular endothelial growth factor and p53 binding protein were among the 17 genes upregulated in the WC-As. Thirty-one genes were upregulated in the SR-Ar including the transforming growth factor-? signaling factor SMAD2 and heat shock protein 90. Genes representing several biochemical pathways were distinctly different between breeds. The most striking divergences were in cytoskeletal remodeling, proteasome activity, cellular respiration, and immune response. Actin cytoskeletal remodeling appears to be one of the first differences between susceptible and resistant breeds, lending support to the smooth muscle cell phenotypic reversion hypothesis of human atherogenesis. PMID:24046414

Anderson, J L; Ashwell, C M; Smith, S C; Shine, R; Smith, E C; Taylor, R L

2013-10-01

263

Associations between surface markers on blood monocytes and carotid atherosclerosis in HIV-positive individuals.  

PubMed

Chronic HIV infection is associated with increased risk of cardiovascular disease (CVD), including in patients with virological suppression. Persistent innate immune activation may contribute to the development of CVD via activation of monocytes in these patients. We investigated whether changes in monocyte phenotype predict subclinical atherosclerosis in virologically suppressed HIV-positive individuals with low cardiovascular risk. We enroled 51 virologically suppressed HIV-positive individuals not receiving protease inhibitors or statins and 49 age-matched uninfected controls in this study. Carotid artery intima-media thickness (cIMT) was used as a surrogate marker for CVD, and traditional risk factors, including Framingham risk scores, were recorded. Markers of monocyte activation (CD14, CD16, CCR2, CX3CR1, CD38, HLA-DR and CD11b) were measured in whole-blood samples by flow cytometry. Associations were assessed using univariate and multivariate median regressions. Median cIMT was similar between HIV-positive and HIV-negative participants (P=0.3), although HIV-positive patients had significantly higher Framingham risk score (P=0.009) and systemic inflammation. Expression of two monocyte markers, CD11b and CX3CR1, independently predicted carotid artery thickness in HIV-positive individuals after controlling for Framingham risk score (P=0.025 and 0.015, respectively). These markers were not predictive of carotid artery thickening in controls. Our study indicates that monocyte surface markers may serve as novel predictors of CVD in HIV-positive individuals and is consistent with an important role for monocyte activation in the progression of HIV-related cardiovascular pathology. PMID:24296810

Westhorpe, Clare L V; Maisa, Anna; Spelman, Tim; Hoy, Jennifer F; Dewar, Elizabeth M; Karapanagiotidis, Sofie; Hearps, Anna C; Cheng, Wan-Jung; Trevillyan, Janine; Lewin, Sharon R; Sviridov, Dmitri; Elliott, Julian H; Jaworowski, Anthony; Dart, Anthony M; Crowe, Suzanne M

2014-02-01

264

[Morphological manifestations of systemic atherosclerosis found in fundus (experimental study)].  

PubMed

Results of angiography and morphology of 32 eyes (16 chinchilla rabbits) with experimental atherosclerosis are presented. N.N. Anichkov and S.S. Khalatova experimental hypercholesterolemia model (1912) was used. The animals were divided into the following groups: initial and advanced atherosclerosis, control group, follow-up 3 and 6 months. After 3 months progressive reduction of perfused retinal vessels and early degenerative changes of neurons and photoreceptors were found. In 6 months these changes became more significant and generalized. Due to ongoing small vessel reduction blood flow went to the major vessels and changed its distribution followed by ischemia of adjacent retina. No changes in choriocapillary layer and retinal pigment epithelium were found in any of groups studied. PMID:23808172

Budzinskaia, M V; Fedorov, A A; Pliukhova, A A; Voevodina, T M; Balatskaia, N V

2013-01-01

265

Hybrid FMT-MRI applied to in vivo atherosclerosis imaging  

PubMed Central

Combining Fluorescent Molecular Tomography (FMT) with anatomical imaging, e.g. MRI facilitates interpreting functional information. Furthermore, using a heterogeneous model for light propagation has been shown in simulations to be superior to homogeneous modeling to quantify fluorescence. Here, we present a combined FMT-MRI system and apply it to heart and aorta molecular imaging, a challenging area due to strong tissue heterogeneity and the presence of air-voids due to lungs. First investigating performance in a phantom and mouse corpse, the MRI-enabled heterogeneous models resulted in an improved quantification of fluorescence reconstructions. The system was then used in mice for in vivo atherosclerosis molecular imaging. Results show that, when using the heterogeneous model, reconstructions were in agreement with the ex vivo measurements. Therefore, the proposed system might serve as a powerful imaging tool for atherosclerosis in mice. PMID:24877023

Li, Baoqiang; Maafi, Foued; Berti, Romain; Pouliot, Philippe; Rhéaume, Eric; Tardif, Jean-Claude; Lesage, Frederic

2014-01-01

266

Hybrid FMT-MRI applied to in vivo atherosclerosis imaging.  

PubMed

Combining Fluorescent Molecular Tomography (FMT) with anatomical imaging, e.g. MRI facilitates interpreting functional information. Furthermore, using a heterogeneous model for light propagation has been shown in simulations to be superior to homogeneous modeling to quantify fluorescence. Here, we present a combined FMT-MRI system and apply it to heart and aorta molecular imaging, a challenging area due to strong tissue heterogeneity and the presence of air-voids due to lungs. First investigating performance in a phantom and mouse corpse, the MRI-enabled heterogeneous models resulted in an improved quantification of fluorescence reconstructions. The system was then used in mice for in vivo atherosclerosis molecular imaging. Results show that, when using the heterogeneous model, reconstructions were in agreement with the ex vivo measurements. Therefore, the proposed system might serve as a powerful imaging tool for atherosclerosis in mice. PMID:24877023

Li, Baoqiang; Maafi, Foued; Berti, Romain; Pouliot, Philippe; Rhéaume, Eric; Tardif, Jean-Claude; Lesage, Frederic

2014-05-01

267

Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis  

PubMed Central

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

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

268

Immune Effector Mechanisms Implicated in Atherosclerosis: From Mice to Humans  

PubMed Central

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

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

2013-01-01

269

Chlamydia pneumoniae and atherosclerosis: the role of mast cells.  

PubMed

Chlamydia pneumoniae (C. pneumoniae), a respiratory pathogen, has been implicated in the pathogenesis of atherosclerosis, an inflammatory progressive disease, characterized by the formation of atherosclerotic plaques. Among several types of inflammatory cells involved in the atherogenesis process, recently particular attention has been directed toward the mast cells. Experimental studies have provided several mechanisms by which C. pneumoniae and mast cells could play a role in all stages of atherosclerosis, from initial inflammatory lesions to plaque rupture. C. pneumoniae, as well as mast cells, may actively participate both through the production of cytokines and matrix-degrading metalloproteinases and by provoking apoptosis of atheroma-associated vascular cells, key events in plaque rupture. This mini-review provides a brief overview on adventitial inflammatory effects of C. pneumoniae and mast cells and their potential role in plaque instability. In addition, in this paper we review the role of mast cells in innate immunity. PMID:19589286

Di Pietro, M; Schiavoni, G; Del Piano, M; Shaik, Y; Boscolo, P; Caraffa, A; Grano, M; Teté, S; Conti, F; Sessa, R

2009-01-01

270

Early carotid atherosclerosis and cardiac diastolic abnormalities in hypertensive subjects  

Microsoft Academic Search

Despite the fact that it is known that hypertension may be associated to early atherosclerosis manifestations, few data are to date available on the relationship between early carotid abnormalities and left ventricular diastolic dysfunction. To address this issue, 142 hypertensive patients (64 females and 78 males) younger than 55 years, at the first diagnosis of mild-to-moderate essential hypertension (WHO\\/ISH criteria),

G Parrinello; D Colomba; P Bologna; A Licata; A Pinto; S Paterna; R Scaglione; G Licata

2004-01-01

271

Endothelial progenitor cells in arthritis-associated vasculogenesis and atherosclerosis  

PubMed Central

Vasculogenesis is the generation of vessels from endothelial progenitor cells (EPCs). Attenuated numbers and function of EPCs associated with defective vasculogenesis are present in rheumatoid arthritis (RA), scleroderma and other autoimmune-inflammatory diseases, which have significant relevance for increased cardio- and cerebrovascular morbidity and mortality in arthritis [1–5]. Stimulation of EPCs and vasculogenesis may be beneficial to prevent and manage atherosclerosis related to arthritis. [1–5]. PMID:19945323

Pákozdi, Angéla; Besenyei, Timea; Paragh, György; Koch, Alisa E.; Szekanecz, Zoltán

2010-01-01

272

Immune regulation in atherosclerosis and the hygiene hypothesis  

Microsoft Academic Search

Atherosclerosis is a chronic inflammatory disease of the arterial wall where both innate and adaptive immune responses contribute\\u000a to disease initiation and progression. The hygiene hypothesis implies that dysregulation of the immune response has led to\\u000a increased susceptibility to immuno-inflammatory diseases. Recent studies established that subtypes of T cells, regulatory\\u000a T cells, actively involved in the maintenance of immunological tolerance,

Hafid Ait-Oufella; Alain Tedgui; Ziad Mallat

273

Fish consumption and early atherosclerosis in middle-aged men  

Microsoft Academic Search

To investigate the association between fish consumption and early atherosclerosis, we analyzed the relationship between fish consumption and average intima-media thickness (AveIMT) by carotid ultrasound in middle-aged Japanese men. Participants were 250 randomly selected, community-based Japanese men aged 40 to 49 years without a prior history of cardiovascular disease. AveIMT was calculated from the mean of 1-cm lengths of both

Yasuyuki Nakamura; Yoshiki Ueno; Shinji Tamaki; Takashi Kadowaki; Tomonori Okamura; Yoshikuni Kita; Naomi Miyamatsu; Akira Sekikawa; Tomoko Takamiya; Aiman El-Saed; Kim Sutton-Tyrrell; Hirotsugu Ueshima

2007-01-01

274

Protective Role of Uncoupling Protein 2 in Atherosclerosis  

Microsoft Academic Search

Background—Uncoupling protein 2 (UCP2) regulates the production of reactive oxygen species in macrophages. However, its role in atherosclerosis is unknown. Methods and Results—Irradiated low-density lipoprotein receptor deficient mice (LDLR-\\/-) were transplanted with bone marrow from either UCP2 deficient mice (Ucp2-\\/-) or wild type mice (Ucp2\\/). Mice were fed an atherogenic diet for 7 weeks. Engraftment of bone marrow cells was

J. Blanc; M. C. Alves-Guerra; B. Esposito; S. Rousset; P. Gourdy; D. Ricquier; A. Tedgui; B. Miroux; Z. Mallat

2003-01-01

275

Serum Vitamin D, Parathyroid Hormone Levels, and Carotid Atherosclerosis  

PubMed Central

Evidence suggests low vitamin D and elevated parathyroid hormone (PTH) concentrations may increase risk for cardiovascular disease. However, little is known about the association between vitamin D or PTH and subclinical atherosclerosis. This cross-sectional study included 654 community-dwelling older adults aged 55–96 years (mean age, 75.5 years) without a history of coronary heart disease, revascularization, or stroke enrolled in the Rancho Bernardo Study who completed a clinic examination in 1997–1999 and provided a blood sample for determination of serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and PTH concentrations. Carotid artery intima-media wall thickness (IMT) was measured as an indicator of atherosclerosis at two sites with B-mode ultrasound. After adjusting for age, sex, smoking, alcohol intake, waist-to-hip ratio, exercise, season of blood draw, diabetes, and hypertension, geometric mean internal carotid IMT (ptrend 0.022), but not common carotid IMT (ptrend 0.834) decreased in a dose-dependent fashion with increasing concentration of 25(OH)D. There was no association of 1,25(OH)2D or PTH with either measure of carotid IMT. In subgroup analyses, 1,25(OH)2D was inversely associated with internal carotid IMT among those with hypertension (p for interaction 0.036). These findings from a population-based cohort of older adults suggest a potential role for vitamin D in the development of subclinical atherosclerosis. Additional research is needed to determine whether vitamin D may influence the progression of atherosclerosis, including the effects of supplementation on the atherosclerotic process. PMID:19539290

Reis, Jared P.; von Mühlen, Denise; Michos, Erin D.; R. Miller, Edgar; Appel, Lawrence J.; Araneta, Maria R.; Barrett-Connor, Elizabeth

2009-01-01

276

Atherosclerosis: a medicolegal tool in exhumed decomposed bodies.  

PubMed

An exhumed body of 40-year-old Hindu man was brought for repostmortem after 10 days of death with history of allegation of assault by mob. The body was in the advanced stage of decomposition with adipocere formation over chest, thigh, and arms. In the present case, atherosclerosis was present in the coronaries and aorta sufficiently enough to deduce the cause of death and to substantiate the first autopsy findings even in highly decomposed exhumed body. PMID:18725791

Ambade, Vipul Namdeorao; Godbole, Hemant Vasant; Batra, Anil Krishnaram

2008-09-01

277

Nikolai N. Anichkov and His Theory of Atherosclerosis  

PubMed Central

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

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

2006-01-01

278

Evaluation of subclinical atherosclerosis in Egyptian psoriatic patients  

PubMed Central

Background Psoriasis (Ps) is a common, relapsing, immune-mediated, inflammatory skin disorder of unknown etiology. Ps is not single organ disease confined to the skin but it is systematic inflammatory condition analogous to other inflammatory immune disorders which are known to have increased risk of heart disease. On other hand, inflammation plays also an important role in the pathogenesis of atherosclerosis. So, there is striking similarity between molecular and inflammatory pathway in Ps and atherosclerosis. Aim of the work Was to assess the presence of subclinical atherosclerosis in patients with Ps by using carotid ultrasonography. Patients and Methods 60 patients with Ps were enrolled in this study after exclusion of traditional cardiovascular risk factors and cardiovascular diseases (CVD). In addition, 20 age and gender matched healthy persons served as controls. Patients were classified according to Ps area and severity index (PASI) score into group I (20 mild patients), group II (20 moderate) and group III (20 severe). The average common carotid artery (CCA) intima media thickness (IMT), internal diameter (ID) and arterial wall mass index (AWMI) were measured using high resolution B- mode ultrasound. Results Psoriatic patients showed statistically significant increase in CCA-IMT (P value 0.001), AWMI (P value 0.010) and significant decrease in ID (P value 0.001), as compared to controls. Conclusion Psoriasis patients could be suggested as a group with an increased atherosclerotic risk especially in older ages with longer duration of Ps. The carotid IMT, ID and AWMI can identify patients with subclinical atherosclerosis who need special follow up to reduce cardiovascular morbidity and mortality. PMID:24719535

Elsheikh, Raghda Ghonimy; Amin, Tarek El-Sayed; El-Ashmawy, Amal Ahmad; Abdalla, Samah Ibrahim Abd El-fttah

2013-01-01

279

IL-25 Inhibits Atherosclerosis Development in Apolipoprotein E Deficient Mice  

PubMed Central

Objective IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s) as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice. Methods and Results Administration of 1 ?g IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apo)E deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC) natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 ?g IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease. Conclusions The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses. PMID:25629516

Mantani, Polyxeni T.; Dunér, Pontus; Bengtsson, Eva; Alm, Ragnar; Ljungcrantz, Irena; Söderberg, Ingrid; Sundius, Lena; To, Fong; Nilsson, Jan; Björkbacka, Harry; Fredrikson, Gunilla Nordin

2015-01-01

280

Epicardial adipose excision slows the progression of porcine coronary atherosclerosis  

PubMed Central

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

2014-01-01

281

Bisphenol A Exposure Enhances Atherosclerosis in WHHL Rabbits  

PubMed Central

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

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

2014-01-01

282

Platelets and their chemokines in atherosclerosis—clinical applications  

PubMed Central

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

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

2014-01-01

283

Atherosclerosis in the Rheumatic Diseases: Compounding the Age Risk  

Microsoft Academic Search

\\u000a In geriatrics, atherosclerosis is a common ­comorbidity, since aging is the strongest risk factor for its development. Patients\\u000a with autoimmune rheumatic disease have an increased risk of atherosclerotic cardiovascular ­disease (ASCVD) morbidity and\\u000a mortality. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) have been studied the most, but other autoimmune\\u000a diseases may confer the risk of ASCVD as well. In

Naoto Yokogawa; Joan M. Von Feldt

284

Atherosclerosis in young Brazilians suffering violent deaths: a pathological study  

PubMed Central

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

2011-01-01

285

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

PubMed

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

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

2006-01-01

286

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

PubMed Central

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

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

2015-01-01

287

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

PubMed

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

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

2015-02-18

288

Protective Role for Properdin in Progression of Experimental Murine Atherosclerosis  

PubMed Central

Genetic, dietary and immune factors contribute to the pathogenesis of atherosclerosis in humans and mice. Complement activation is an integral part of the innate immune defence but also shapes cellular responses and influences directly triglyceride synthesis. Deficiency of Factor B of the alternative pathway (AP) of complement is beneficial in LDLR?/? mice fed a high fat diet. The serum glycoprotein properdin is a key positive regulator of the AP but has not been studied in experimental atherosclerosis. Atherosclerosis was assessed after feeding low fat (LFD) or high fat (HFD) Western type diets to newly generated LDLR?/? ProperdinKO (LDLR?/?PKO) and LDLR?/?PWT mice. Lipids, lymphocytes and monocytes were similar among genotypes, genders and diets. Complement C3, but not C3adesarg, levels were enhanced in LDLR?/?PKO mice regardless of diet type or gender. Non-esterified fatty acids (NEFA) were decreased in male LDLR?/?PKO fed a HFD compared with controls. All mice showed significant atherosclerotic burden in aortae and at aortic roots but male LDLR?/? mice fed a LFD were affected to the greatest extent by the absence of properdin. The protective effect of properdin expression was overwhelmed in both genders of LDLR?/?mice when fed a HFD. We conclude that properdin plays an unexpectedly beneficial role in the development and progression of early atherosclerotic lesions. PMID:24667818

Byrne, Simon; Hughes, Timothy; Jayanthi, Archana; Guschina, Irina; Harwood, John; Cianflone, Katherine; Francis, Sheila

2014-01-01

289

Targeting sortilin in immune cells reduces proinflammatory cytokines and atherosclerosis  

PubMed Central

Genome-wide association studies have identified a link between genetic variation at the human chromosomal locus 1p13.3 and coronary artery disease. The gene encoding sortilin (SORT1) has been implicated as the causative gene within the locus, as sortilin regulates hepatic lipoprotein metabolism. Here we demonstrated that sortilin also directly affects atherogenesis, independent of its regulatory role in lipoprotein metabolism. In a mouse model of atherosclerosis, deletion of Sort1 did not alter plasma cholesterol levels, but reduced the development of both early and late atherosclerotic lesions. We determined that sortilin is a high-affinity receptor for the proinflammatory cytokines IL-6 and IFN-?. Moreover, macrophages and Th1 cells (both of which mediate atherosclerotic plaque formation) lacking sortilin had reduced secretion of IL-6 and IFN-?, but not of other measured cytokines. Transfer of sortilin-deficient BM into irradiated atherosclerotic mice reduced atherosclerosis and systemic markers of inflammation. Together, these data demonstrate that sortilin influences cytokine secretion and that targeting sortilin in immune cells attenuates inflammation and reduces atherosclerosis. PMID:25401472

Mortensen, Martin B.; Kjolby, Mads; Gunnersen, Stine; Larsen, Jakob V.; Palmfeldt, Johan; Falk, Erling; Nykjaer, Anders; Bentzon, Jacob F.

2014-01-01

290

Atherosclerosis and interferon-?: New insights and therapeutic targets  

PubMed Central

Atherosclerosis is considered to be a chronic inflammatory disease of the arterial wall. Atherogenesis is accompanied by local production and release of inflammatory mediators, for which the macrophage is a major source. The proinflammatory cytokine, interferon (IFN)-? derived from T cells, is expressed at high levels in atherosclerotic lesions. IFN-? is the classic macrophage-activating factor, vital for both innate and adaptive immunity. It primes macrophages to produce chemokines and cytotoxic molecules and induces expression of genes that regulate lipid uptake. IFN-? is a key trigger for the formation and release of reactive oxygen species. IFN-? has important effects on endothelial cells, promoting expression of adhesion molecules. Atherogenic effects of IFN-? have been shown in murine models where exogenous administration enhances atherosclerotic lesion formation while knockout of IFN-? or its receptor reduces lesion size. IFN-? signaling is largely mediated by a Janus kinase (JAK) to signal transduction and activator of transcription (STAT)1 cytosolic factor pathway. A clear understanding of IFN-? effects on atherogenesis should enable development of novel targeted interventions for clinical use in the prevention and treatment of atherosclerosis. This review will discuss the actions of the cytokine IFN-? and its complex effects on cells involved in atherosclerosis. PMID:23916809

Voloshyna, Iryna; Littlefield, Michael J.; Reiss, Allison B.

2013-01-01

291

Lasting monitoring of immune state in patients with coronary atherosclerosis  

NASA Astrophysics Data System (ADS)

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

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

2007-02-01

292

Iron overload diminishes atherosclerosis in apoE-deficient mice.  

PubMed

It has been proposed that elevated levels of tissue iron increase the risk for atherosclerosis, perhaps by favoring the formation of pro-atherogenic oxidized LDL. Working with apoE-deficient (apoE(-/-)) mice, which do not require a high-fat diet to develop atherosclerosis, we compared the effects of standard diet (0.02% iron) or a 2% carbonyl iron diet. After 24 weeks, mice fed the 2% carbonyl iron diet had twice as much iron in their plasma, a ninefold increase in bleomycin-detectable free iron in their plasma, and ten times as much iron in their livers as control mice. Dietary iron overload caused a modest (30%) rise in plasma triglyceride and cholesterol. Nevertheless, this regimen did not exacerbate, but rather reduced the severity of atherosclerosis by 50%, and it failed to elevate hepatic levels of heme oxygenase mRNA, which is induced by many different oxidative insults in vitro. Moreover, hepatic levels of protein-bound dityrosine and ortho-tyrosine, two markers of metal-catalyzed oxidative damage in vitro, failed to rise in iron-overloaded animals. Our observations suggest that elevated serum and tissue levels of iron are not atherogenic in apoE(-/-) mice. Moreover, they call into question the hypothesis that elevated levels of tissue iron promote LDL oxidation and oxidative stress in vivo. PMID:11413162

Kirk, E A; Heinecke, J W; LeBoeuf, R C

2001-06-01

293

Involvement of heparanase in atherosclerosis and other vessel wall pathologies.  

PubMed

Heparanase, the sole mammalian endoglycosidase degrading heparan sulfate, is causally involved in cancer metastasis, angiogenesis, inflammation and kidney dysfunction. Despite the wide occurrence and impact of heparan sulfate proteoglycans in vascular biology, the significance of heparanase in vessel wall disorders is underestimated. Blood vessels are highly active structures whose morphology rapidly adapts to maintain vascular function under altered systemic and local conditions. In some pathologies (restenosis, thrombosis, atherosclerosis) this normally beneficial adaptation may be detrimental to overall function. Enzymatic dependent and independent effects of heparanase on arterial structure mechanics and repair closely regulate arterial compliance and neointimal proliferation following endovascular stenting. Additionally, heparanase promotes thrombosis after vascular injury and contributes to a pro-coagulant state in human carotid atherosclerosis. Importantly, heparanase is closely associated with development and progression of atherosclerotic plaques, including stable to unstable plaque transition. Consequently, heparanase levels are markedly increased in the plasma of patients with acute myocardial infarction. Noteworthy, heparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression towards vulnerability. Together, heparanase emerges as a regulator of vulnerable lesion development and potential target for therapeutic intervention in atherosclerosis and related vessel wall complications. PMID:23499530

Vlodavsky, Israel; Blich, Miry; Li, Jin-Ping; Sanderson, Ralph D; Ilan, Neta

2013-06-24

294

Involvement of heparanase in atherosclerosis and other vessel wall pathologies  

PubMed Central

Heparanase, the sole mammalian endoglycosidase degrading heparan sulfate, is causally involved in cancer metastasis, angiogenesis, inflammation and kidney dysfunction. Despite the wide occurrence and impact of heparan sulfate proteoglycans in vascular biology, the significance of heparanase in vessel wall disorders is underestimated. Blood vessels are highly active structures whose morphology rapidly adapts to maintain vascular function under altered systemic and local conditions. In some pathologies (restenosis, thrombosis, atherosclerosis) this normally beneficial adaptation may be detrimental to overall function. Enzymatic dependent and independent effects of heparanase on arterial structure mechanics and repair closely regulate arterial compliance and neointimal proliferation following endovascular stenting. Additionally, heparanase promotes thrombosis after vascular injury and contributes to a pro-coagulant state in human carotid atherosclerosis. Importantly, heparanase is closely associated with development and progression of atherosclerotic plaques, including stable to unstable plaque transition. Consequently, heparanase levels are markedly increased in the plasma of patients with acute myocardial infarction. Noteworthy, heparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression towards vulnerability. Together, heparanase emerges as a regulator of vulnerable lesion development and potential target for therapeutic intervention in atherosclerosis and related vessel wall complications. PMID:23499530

Vlodavsky, Israel; Blich, Miry; Li, Jin-Ping; Sanderson, Ralph D.; Ilan, Neta

2014-01-01

295

Habitual fish intake and clinically silent carotid atherosclerosis  

PubMed Central

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

2014-01-01

296

Under-expression of ?8 integrin aggravates experimental atherosclerosis.  

PubMed

Integrins play an important role in vascular biology. The ?8 integrin chain attenuates smooth muscle cell migration but its functional role in the development of atherosclerosis is unclear. Therefore, we studied the contribution of ?8 integrin to atherosclerosis and vascular remodelling. We hypothesized that ?8 integrin expression is reduced in atherosclerotic lesions, and that its under-expression leads to a more severe course of atherosclerosis. ?8 Integrin was detected by immunohistochemistry and qPCR and ?8 integrin-deficient mice were used to induce two models of atherosclerotic lesions. First, ligation of the carotid artery led to medial thickening and neointima formation, which was quantified in carotid cross-sections. Second, after crossing into ApoE-deficient mice, the formation of advanced vascular lesions with atherosclerotic plaques was quantified in aortic en face preparations stained with Sudan IV. Parameters of renal physiology and histopathology were assessed: ?8 integrin was detected in the media of human and murine vascular tissue and was down-regulated in arteries with advanced atherosclerotic lesions. In ?8 integrin-deficient mice (?8(-/-) ) as well as ?8(+/-) and ?8(+/+) littermates, carotid artery ligation increased media:lumen ratios in all genotypes, with higher values in ligated ?8(-/-) and ?8(+/-) compared to ligated ?8(+/+) animals. Carotid artery ligation increased smooth muscle cell number in the media of ?8(+/+) mice and, more prominently, of ?8(-/-) or ?8(+/-) mice. On an ApoE(-/-) background, ?8(+/-) and ?8(-/-) mice developed more atherosclerotic plaques than ?8(+/+) mice. ?8 Integrin expression was reduced in ?8(+/-) animals. Renal damage with increased serum creatinine and glomerulosclerosis was detected in ?8(-/-) mice only. Thus, under-expression of ?8 integrin aggravates vascular lesions, while a complete loss of ?8 integrin results in reduced renal mass and additional renal disease in the presence of generalized atherosclerosis. Our data support the hypothesis that integrin ?8?1 has a protective role in arterial remodelling and atherosclerosis. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:25511181

Menendez-Castro, Carlos; Cordasic, Nada; Neureiter, Daniel; Amann, Kerstin; Marek, Ines; Volkert, Gudrun; Stintzing, Sebastian; Jahn, Angelika; Rascher, Wolfgang; Hilgers, Karl F; Hartner, Andrea

2015-05-01

297

Atherosclerosis associated with pericardial effusion in a central bearded dragon (Pogona vitticeps).  

PubMed

Atherosclerosis is a common disease in pet birds, particularly in psittacines, and is frequently found when performing postmortem examinations on adult and old dogs, in which it is mainly associated with endocrine diseases, such as hypothyroidism and diabetes mellitus. However, atherosclerosis is poorly documented in reptiles and consequently poorly understood. In the current case report, atherosclerosis and pericardial effusion were diagnosed in a 2-year-old male central bearded dragon (Pogona vitticeps) based on ultrasound visualization, necropsy, and histologic examination. PMID:20807945

Schilliger, Lionel; Lemberger, Karin; Chai, Norin; Bourgeois, Aude; Charpentier, Maud

2010-09-01

298

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

Microsoft Academic Search

.   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

S. R. Basavaraju; T. D. Jones

1998-01-01

299

Regional predisposition to atherosclerosis – An interplay between local hemodynamics, endothelial cells and resident intimal dendritic cells  

Microsoft Academic Search

\\u000a Atherosclerosis develops in regions of the arterial tree with disturbed hemodynamics, but the underlying mechanisms of regional\\u000a susceptibility to atherosclerosis are not fully understood. In this review, we summarize studies on intimal gene expression\\u000a and cellular composition in atherosclerosis-susceptible regions of the normal mouse aorta, and discuss the implications to\\u000a atherogenesis. Low-grade inflammation and accumulation of bone marrow-derived subendothelial resident

Jenny Jongstra-Bilen; Myron I. Cybulsky

300

Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: a combined transcriptomics and metabolomics analysis  

Microsoft Academic Search

Background  Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and\\u000a an inflammatory component. It is unclear where and how the inflammatory component develops. To assess the role of the liver\\u000a in the evolution of inflammation, we treated ApoE*3Leiden mice with cholesterol-free (Con), low (LC; 0.25%) and high (HC;\\u000a 1%) cholesterol diets, scored early atherosclerosis and profiled

Robert Kleemann; Lars Verschuren; Marjan J van Erk; Yuri Nikolsky; Nicole HP Cnubben; Elwin R Verheij; Age K Smilde; Henk FJ Hendriks; Susanne Zadelaar; Graham J Smith; Valery Kaznacheev; Tatiana Nikolskaya; Anton Melnikov; Eva Hurt-Camejo; Jan van der Greef; Ben van Ommen; Teake Kooistra

2007-01-01

301

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 ...

302

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

E-print Network

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

Chan, Raymond C

2001-01-01

303

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

PubMed

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

Bavelaar, F J; Beynen, A C

2003-01-01

304

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

PubMed

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

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

305

Yucatan miniature swine as a model for diet-induced atherosclerosis.  

PubMed

Nine female Yucatan miniature swine, a breed not previously evaluated for their potential usefulness as a model for experimental atherosclerosis studies, were fed a high-fat, high-cholesterol diet for 10-12 months. These swine and 4 control (low-fat, low-cholesterol-fed) swine underwent a complete necropsy at the end of this period to characterize the atherosclerosis both by gross and microscopic examination. Cholesterol feeding led to elevated serum cholesterol levels and the development of accelerated atherosclerosis. Control animals on a low-cholesterol diet had little gross or microscopic atherosclerosis. All of the cholesterol-fed swine had more extensive atherosclerosis than any of the controls by gross inspection of the Sudan-stained arterial tissue. There was individual variation suggesting the interaction of factors in addition to the plasma cholesterol which determine the extent and severity of atherosclerosis. However, it was possible to show a positive correlation between hypercholesterolemia and (1) intimal thickening in the terminal abdominal aorta and mesenteric artery, and (2) increased fat deposition in the mesenteric artery. The cholesterol-induced atherosclerosis was characterized by the deposition of lipid in and around cells. Complicated atherosclerotic lesions similar to human atherosclerosis were characterized by marked animal proliferation, necrosis, cholesterol crystal deposition, and calcification. It is concluded that the Yucatan miniature swine represent an important additional animal model in which to study certain aspects of atherosclerosis. PMID:7092978

Reitman, J S; Mahley, R W; Fry, D L

1982-05-01

306

ARG2 impairs endothelial autophagy through regulation of MTOR and PRKAA/AMPK signaling in advanced atherosclerosis.  

PubMed

Impaired autophagy function and enhanced ARG2 (arginase 2)-MTOR (mechanistic target of rapamycin) crosstalk are implicated in vascular aging and atherosclerosis. We are interested in the role of ARG2 and the potential underlying mechanism(s) in modulation of endothelial autophagy. Using human nonsenescent "young" and replicative senescent endothelial cells as well as Apolipoprotein E-deficient (apoe(-/-)Arg2(+/+)) and Arg2-deficient apoe(-/-) (apoe(-/-)arg2(-/-)) mice fed a high-fat diet for 10 wk as the atherosclerotic animal model, we show here that overexpression of ARG2 in the young cells suppresses endothelial autophagy with concomitant enhanced expression of RICTOR, the essential component of the MTORC2 complex, leading to activation of the AKT-MTORC1-RPS6KB1/S6K1 (ribosomal protein S6 kinase, 70kDa, polypeptide 1) cascade and inhibition of PRKAA/AMPK (protein kinase, AMP-activated, ? catalytic subunit). Expression of an inactive ARG2 mutant (H160F) had the same effect. Moreover, silencing RPS6KB1 or expression of a constitutively active PRKAA prevented autophagy suppression by ARG2 or H160F. In senescent cells, enhanced ARG2-RICTOR-AKT-MTORC1-RPS6KB1 and decreased PRKAA signaling and autophagy were observed, which was reversed by silencing ARG2 but not by arginase inhibitors. In line with the above observations, genetic ablation of Arg2 in apoe(-/-) mice reduced RPS6KB1, enhanced PRKAA signaling and endothelial autophagy in aortas, which was associated with reduced atherosclerosis lesion formation. Taken together, the results demonstrate that ARG2 impairs endothelial autophagy independently of the L-arginine ureahydrolase activity through activation of RPS6KB1 and inhibition of PRKAA, which is implicated in atherogenesis. PMID:25484082

Xiong, Yuyan; Yepuri, Gautham; Forbiteh, Michael; Yu, Yi; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

2014-12-01

307

MafB promotes atherosclerosis by inhibiting foam-cell apoptosis  

NASA Astrophysics Data System (ADS)

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

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

2014-01-01

308

Circulating concentrations of GLP-1 are associated with coronary atherosclerosis in humans  

PubMed Central

Background GLP-1 is an incretine hormone which gets secreted from intestinal L-cells in response to nutritional stimuli leading to pancreatic insulin secretion and suppression of glucagon release. GLP-1 further inhibits gastric motility and reduces appetite which in conjunction improves postprandial glucose metabolism. Additional vasoprotective effects have been described for GLP-1 in experimental models. Despite these vasoprotective actions, associations between endogenous levels of GLP-1 and cardiovascular disease have yet not been investigated in humans which was the aim of the present study. Methods GLP-1 serum levels were assessed in a cohort of 303 patients receiving coronary CT-angiography due to typical or atypical chest pain. Results GLP-1 was found to be positively associated with total coronary plaque burden in a fully adjusted model containing age, sex, BMI, hypertension, diabetes mellitus, smoking, triglycerides, LDL-C (low density lipoprotein cholesterol), hsCRP (high-sensitive C-reactive protein), and eGFR (estimated glomerular filtration rate) (OR: 2.53 (95% CI: 1.12 – 6.08; p?=?0.03). Conclusion Circulating GLP-1 was found to be positivity associated with coronary atherosclerosis in humans. The clinical relevance of this observation needs further investigations. PMID:23953602

2013-01-01

309

A Crucial Role for CDC42 in Senescence-Associated Inflammation and Atherosclerosis  

PubMed Central

Risk factors for atherosclerosis accelerate the senescence of vascular endothelial cells and promote atherogenesis by inducing vascular inflammation. A hallmark of endothelial senescence is the persistent up-regulation of pro-inflammatory genes. We identified CDC42 signaling as a mediator of chronic inflammation associated with endothelial senescence. Inhibition of CDC42 or NF-?B signaling attenuated the sustained up-regulation of pro-inflammatory genes in senescent human endothelial cells. Endothelium-specific activation of the p53/p21 pathway, a key mediator of senescence, also resulted in up-regulation of pro-inflammatory molecules in mice, which was reversed by Cdc42 deletion in endothelial cells. Likewise, endothelial-specific deletion of Cdc42 significantly attenuated chronic inflammation and plaque formation in atherosclerotic mice. While inhibition of NF-?B suppressed the pro-inflammatory responses in acute inflammation, the influence of Cdc42 deletion was less marked. Knockdown of cdc-42 significantly down-regulated pro-inflammatory gene expression and restored the shortened lifespan to normal in mutant worms with enhanced inflammation. These findings indicate that the CDC42 pathway is critically involved in senescence-associated inflammation and could be a therapeutic target for chronic inflammation in patients with age-related diseases without compromising host defenses. PMID:25057989

Ito, Takashi K.; Yokoyama, Masataka; Yoshida, Yohko; Nojima, Aika; Kassai, Hidetoshi; Oishi, Kengo; Okada, Sho; Kinoshita, Daisuke; Kobayashi, Yoshio; Fruttiger, Marcus; Aiba, Atsu; Minamino, Tohru

2014-01-01

310

Hypercysteinemia promotes atherosclerosis by reducing protein S-nitrosylation.  

PubMed

Protein S-nitrosylation plays important role in the regulation of cardiovascular functions in nitric oxide (NO) Pathway. Hypercysteinemia (HHcy) is an independently risk factor for atherosclerosis. We hypothesized that HHcy promotes atherosclerosis by reducing level of vascular protein S-nitrosylation. The aim of present study is to investigate effect of HHcy on vascular protein S-nitrosylation. A total of 45 male apoE-/- mice were randomly divided into three groups. The control group was fed a Western-type diet. The HHcy group was fed a diet containing 4.4% l-methionine, and the HHcy+NONOate group was fed a diet containing 4.4% l-methionine and administrated NONOate (ip). Human umbilical vein endothelial cells were performed for in vitro experiment. Plasma lipids were measured every 4 weeks. After 12 weeks, aortic atherosclerotic lesion areas were detected as well as cellular components. The levels of plasma homocysteine (Hcy) and NO were measured. S-nitrosylation was detected using immunofluorescence, and further confirmed by biotin switch method. We found that compared with the control group, Hcy levels, and atherosclerotic plaque, and content of vascular smooth muscle cells and macrophages in lesions significantly increased, and levels of NO significantly decreased in the HHcy group. However, NONOate reverses this effect. In addition, Hcy significantly reduced protein S-nitrosylation in human umbilical vein endothelial cells. This reduction of protein S-nitrosylation was accompanied by reduced levels of NO. Our results suggested that Hcy promoted atherosclerosis by inhibiting vascular protein S-nitrosylation. PMID:25776509

Chen, Yulong; Liu, Ruihan; Zhang, Guangwei; Yu, Qi; Jia, Min; Zheng, Chao; Wang, Yanli; Xu, Cangbao; Zhang, Yaping; Liu, Enqi

2015-03-01

311

The pigeon (Columba livia) model of spontaneous atherosclerosis.  

PubMed

Multiple animal models have been employed to study human atherosclerosis, the principal cause of mortality in the United States. Each model has individual advantages related to specific pathologies. Initiation, the earliest disease phase, is best modeled by the White Carneau (WC-As) pigeon. Atherosclerosis develops spontaneously in the WC-As without either external manipulation or known risk factors. Furthermore, susceptibility is caused by a single gene defect inherited in an autosomal recessive manner. The Show Racer (SR-Ar) pigeon is resistant to atherosclerosis. Breed differences in the biochemistry and metabolism of celiac foci cells have been described. For example, WC-As have lower oxidative metabolism but higher amounts of chondroitin-6-sulfate and nonesterified fatty acids compared with SR-Ar. Gene expression in aortic smooth muscle cells was compared between breeds using representational difference analysis and microarray analysis. Energy metabolism and cellular phenotype were the chief gene expression differences. Glycolysis and synthetic cell types were related to the WC-As but oxidative metabolism and contractile cell types were related to the SR-Ar. Rosiglitazone, a PPAR? agonist, blocked RNA binding motif (RBMS1) expression in WC-As cells. The drug may act through the c-myc oncogene as RBMS1 is a c-myc target. Proteomic tests of aortic smooth muscle cells supported greater glycosylation in the WC-As and a transforming growth factor ? effect in SR-Ar. Unoxidized fatty acids build up in WC-As cells because of their metabolic deficiency, ultimately preventing the contractile phenotype in these cells. The single gene responsible for the disease is likely regulatory in nature. PMID:25214557

Anderson, J L; Smith, S C; Taylor, R L

2014-11-01

312

Fluorescence spectroscopic detection of virus-induced atherosclerosis  

NASA Astrophysics Data System (ADS)

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.

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

1994-07-01

313

Experimental diet-induced atherosclerosis in Quaker parrots (Myiopsitta monachus).  

PubMed

Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions were histologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans. PMID:23696447

Beaufrère, H; Nevarez, J G; Wakamatsu, N; Clubb, S; Cray, C; Tully, T N

2013-11-01

314

Biomarkers of Cardiovascular Stress and Subclinical Atherosclerosis in the Community  

PubMed Central

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

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

2014-01-01

315

Untreated masked hypertension and carotid atherosclerosis: A meta-analysis.  

PubMed

Abstract Aim. Masked hypertension (MH) is recognized as a clinical entity with an unfavorable cardiovascular prognosis; a limited number of reports, however, investigated the impact of this condition on subclinical vascular damage. We performed a meta-analysis aimed at evaluating the association of MH with subclinical carotid atherosclerosis in initially untreated subjects. Design. Studies were identified by the following search terms: "masked hypertension", "isolated clinic normotension", "white coat normotension", "carotid artery", "carotid atherosclerosis", "carotid intima-media thickness", "carotid damage" and "carotid thickening". Full articles published in English language reporting data from studies performed in untreated adult individuals were considered. Results. Overall, 2752 untreated subjects (1039 normotensive, 497 MH and 766 hypertensive individuals) of both genders were included in five studies (sample size range 18-222 for MH participants). Common carotid intima-media thickness (IMT) showed a progressive increase from normotensive (681 ± 24 ?m) to MH (763 ± 57 ?m) (standardized mean difference, SMD: 0.51 ± 0.19, 95% CI 0.13-0.89, p < 0.01) and to sustained hypertensive subjects (787 ± 58 ?m) (SMD: 0.33 ± 0.07, 95% CI 0.20-0.46, p < 0.01). The statistical difference between MH and NT became borderline after correction for publication bias. A sensitivity analysis showed that the final result was not substantially affected by a single study effect. Conclusions. Our findings support the view that MH subjects tend to have a higher risk of developing early carotid atherosclerosis than their true normotensive counterparts. From a practical perspective, the ultrasound search of preclinical carotid disease may improve cardiovascular risk stratification and decision making strategies in these subjects. PMID:25608631

Cuspidi, Cesare; Sala, Carla; Tadic, Marijana; Rescaldani, Marta; De Giorgi, Giuseppe Antonio; Grassi, Guido; Mancia, Giuseppe

2015-04-01

316

Obstructive sleep apnea, immuno-inflammation, and atherosclerosis  

PubMed Central

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder leading to cardiovascular and metabolic complications. OSA is also a multicomponent disorder, with intermittent hypoxia (IH) as the main trigger for the associated cardiovascular and metabolic alterations. Indeed, recurrent pharyngeal collapses during sleep lead to repetitive sequences of hypoxia-reoxygenation. This IH induces several consequences such as hemodynamic, hormono-metabolic, oxidative and immuno-inflammatory alterations that may interact and aggravate each other, resulting in artery changes, from adaptive to degenerative atherosclerotic remodeling. Atherosclerosis has been found in OSA patients free of other cardiovascular risk factors, and is related to the severity of nocturnal hypoxia. Early stages of artery alteration, including functional and structural changes, have been evidenced in both OSA patients and rodents experimentally exposed to IH. Impaired vasoreactivity with endothelial dysfunction and/or increased vasoconstrictive responses due to sympathetic, endothelin and renin-angiotensin systems have been reported and also contribute to vascular remodeling and inflammation. Oxidative stress, inflammation and vascular remodeling can be directly triggered by IH, further aggravated by the OSA-associated hormono-metabolic alterations, such as insulin resistance, dyslipidemia and adipokine imbalance. As shown in OSA patients and in the animal model, genetic susceptibility, comorbidities (obesity) and life habits (high fat diet) may aggravate atherosclerosis development or progression. The intimate molecular mechanisms are still largely unknown, and their understanding may contribute to delineate new targets for prevention strategies and/or development of new treatment of OSA-related atherosclerosis, especially in patients at risk for cardiovascular disease. PMID:19404644

Arnaud, Claire; Dematteis, Maurice; Pepin, Jean-Louis; Baguet, Jean-Philippe; Lévy, Patrick

2009-01-01

317

Carotid Atherosclerosis and 10-year Changes in Cognitive Function  

PubMed Central

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

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

2012-01-01

318

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

E-print Network

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

McQuade, D. Tyler

319

Relationships of Cerebral MRI Findings to Ultrasonographic Carotid Atherosclerosis in Older Adults The Cardiovascular Health Study  

Microsoft Academic Search

Cerebral magnetic resonance imaging (MRI) has demonstrated a high prevalence of infarct-like lesions, white matter hyperintensities, and evidence of cerebral atrophy in older adults. While these findings are generally believed to be related to ischemia and atherosclerosis, their relationship to atherosclerosis in the carotid arteries remains to be explored. Study subjects were part of the multicenter Cardiovascular Health Study, a

Teri A. Manolio; Gregory L. Burke; Daniel H. O'Leary; Gregory Evans; Norman Beauchamp; Laurie Knepper; Beverly Ward

2010-01-01

320

Postchallenge hyperglycemia but not hyperinsulinemia is associated with angiographically documented coronary atherosclerosis in Korean subjects  

Microsoft Academic Search

Although hyperinsulinemia has attracted considerable attention as a possible risk factor for coronary artery disease (CAD), previous studies have not shown consistent results. Hyperglycemia could be an alternative explanation for the association between type 2 diabetes and atherosclerosis. Since previous studies have been mostly lacking coronary angiographic data, we analyzed the relationship between the presence and severity of coronary atherosclerosis

Hong-Kyu Kim; Sung-Kwang Lee; Chan-Jong Suh; Hyo-Joong Yoon; Ki-Young Lee; Hye-Young Park; Moon-Ho Kang

2003-01-01

321

The Relation Between Diet, Plasma Cholesterol and Atherosclerosis in Pigeons, Quails and Chickens  

Microsoft Academic Search

A literature survey was conducted to determine the relationship between plasma cholesterol concentrations and the severity of diet-induced atherosclerosis in pigeons, quails and chickens. A direc t relationship was found between plasma cholesterol and atherosclerosis as induced by cholesterol feeding. In general, dietary polyunsaturated fatty acids versus saturated fatty acids lowered plasma cholesterol concentrations in the three avian species

2004-01-01

322

Atherosclerosis in childhood and adolescent type 1 diabetes: early disease, early treatment?  

Microsoft Academic Search

Autopsy studies have shown that atherosclerosis begins in adolescence in otherwise healthy individuals, and imaging techniques have shown that atherosclerosis develops earlier and is more prevalent in children with diabetes than in age-matched healthy controls. Cardiovascular disease has now overtaken diabetic nephropathy as the leading cause of premature mortality in young adults with diabetes, and the emphasis on disease prevention

K. Dahl-Jørgensen; J. R. Larsen; K. F. Hanssen

2005-01-01

323

Role of endogenous androgens on carotid atherosclerosis in non-obese postmenopausal women  

Microsoft Academic Search

BackgroundRecent randomized trials on hormone replacement therapy in postmenopausal women raised many doubts about their role in cardiovascular disease prevention. Therefore the role of other sex hormones needed to be investigated. In particular androgens seem to have a protective role on atherosclerosis. The present study was performed to assess the role of endogenous sex hormones on carotid atherosclerosis in postmenopausal

T. Montalcini; G. Gorgone; C. Gazzaruso; G. Sesti; F. Perticone; A. Pujia

2007-01-01

324

Hypertension and Atherosclerosis: Advanced Glycation End Products—A Common Link  

Microsoft Academic Search

The vascular diseases, hypertension and atherosclerosis, affect millions of individuals worldwide accounting for a large number of deaths globally. They share similar risk factors, and modify vascular structure and function. Although increased blood pressure itself can contribute to vascular injury, the relationship between hypertension and atherosclerosis likely has a biochemical component. We suggest that aldehyde conjugates, formed as a result

Sudesh Vasdev; Vicki Gill

325

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

Microsoft Academic Search

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

Louise E Full; Cristina Ruisanchez; Claudia Monaco

2009-01-01

326

Atherosclerosis after Coronary Artery Bypass Surgery: Results of Recent Studies and Recommendations Regarding Prevention  

Microsoft Academic Search

Atherosclerosis is the most frequent cause of occlusion of aortocoronary saphenousvein grafts between 5 and 10 years after coronary artery bypass surgery. The typical atherosclerotic plaque appears between 1 and 3 years after operation and, at a mean of 5 years, histologic changes of atherosclerosis are present in 21 % of grafts and in 27% of patients. Only approximately 60%

Martial G. Bourassa; Lucien Campeau; Jacques Lespérance; Charles Solymoss

1986-01-01

327

Cardiovasc Res . Author manuscript A CD31-derived peptide prevents angiotensin II-induced atherosclerosis  

E-print Network

; pharmacology ; Antigens, CD31 ; pharmacology ; Aortic Aneurysm, Abdominal ; chemically induced ; genetics of atherosclerosis towards its complications such as coronary plaque1 thrombosis and abdominal aortic aneurysms (AAA-induced atherosclerosis progression and aneurysm formation Giulia Fornasa 1 , Marc Clement 1 , Emilie Groyer 1 , Anh

Paris-Sud XI, Université de

328

Insights into Atherosclerosis Using Nanotechnology Ashwath Jayagopal & MacRae F. Linton & Sergio Fazio &  

E-print Network

2010 Abstract A developing forefront in vascular disease research is the application of nanotechnology in atherosclerosis. Promising re- search in this field over the past decade has resulted in the preclinical management of atherosclerosis, drawing upon recent preclinical studies relevant to diagnosis and treatment

329

Low-densitylipoprotein oxidation,antioxidants, and atherosclerosis:a clinicalbiochemistry perspective  

Microsoft Academic Search

Cardiovascular disease is the leading cause of mortality in westernized populations. An increased concentration of plasma low-density lipoprotein (LDL) cholesterol consti- tutes a major risk factor for atherosclerosis. Several lines of evidence support a role for oxidatively modified LDL in atherosclerosis and for its in vivo existence. Antioxidants have been shown to decrease atherosclerotic lesion forma- tion in animal models

ISHWARLAL JIALAL

330

Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice  

Microsoft Academic Search

Atherosclerosis is a chronic inflammatory disease, and is the primary cause of heart disease and stroke in Western countries. Derivatives of cannabinoids such as delta-9-tetrahydrocannabinol (THC) modulate immune functions and therefore have potential for the treatment of inflammatory diseases. We investigated the effects of THC in a murine model of established atherosclerosis. Oral administration of THC (1mgkg-1 per day) resulted

Sabine Steffens; Niels R. Veillard; Claire Arnaud; Graziano Pelli; Fabienne Burger; Christian Staub; Andreas Zimmer; Jean-Louis Frossard; François Mach

2005-01-01

331

Large brachial and common carotid artery diameter in postmenopausal women with carotid atherosclerosis  

Microsoft Academic Search

Background and purpose: It is recognized that arteries can enlarge to compensate atherosclerosis. The role of diameter enlargement of unaffected arteries is not well known. We hypothesized that brachial and common carotid arteries diameters were larger in subjects with carotid atherosclerosis compared to subjects without these lesions. 12 13 14 Methods: We measured diameters in the common carotid and brachial

Tiziana Montalcini; Gaetano Gorgone; Carmine Gazzaruso; Giorgio Sesti; Francesco Perticone; Arturo Pujia

332

Large brachial and common carotid artery diameter in postmenopausal women with carotid atherosclerosis  

Microsoft Academic Search

Background and purposeIt is recognized that arteries can enlarge to compensate atherosclerosis. The role of diameter enlargement of unaffected arteries is not well known. We hypothesized that brachial and common carotid arteries diameters were larger in subjects with carotid atherosclerosis compared to subjects without these lesions.

Tiziana Montalcini; Gaetano Gorgone; Carmine Gazzaruso; Giorgio Sesti; Francesco Perticone; Arturo Pujia

2008-01-01

333

Relation of low bone mineral density and carotid atherosclerosis in postmenopausal women  

Microsoft Academic Search

Due to the lack of convincing data about the association between atherosclerosis and osteoporosis, we evaluated the association between carotid atherosclerosis and bone mineral density in a sample of apparently healthy postmenopausal women who underwent health-screening in our hospital. We also evaluated a bone turnover marker, osteocalcin; we divided the population into 2 groups according to osteocalcin levels. We found

Tiziana Montalcini; Vittorio Emanuele; Roberto Ceravolo; Gaetano Gorgone; Giorgio Sesti; Franco Perticone; Arturo Pujia

2004-01-01

334

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

PubMed

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

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

2008-09-01

335

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

Microsoft Academic Search

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

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

336

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

PubMed

The effects of taurine supplementation on the serum cholesterol levels and the progression of atherosclerosis were investigated in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail. The ingestion of a high-cholesterol diet containing 1% cholesterol by LAP quails for 60 days resulted in a marked elevation in serum non-HDL cholesterol and triglyceride, as well as severe aortic lesions with lipid droplets. An immunohistochemical study showed that the lesion consisted of mainly lipid-rich macrophages and T cells. Sixty-day taurine supplementation (1% in drinking tap water) to LAP quails fed high-cholesterol diet containing 1% cholesterol significantly reduced serum non-HDL cholesterol from 4,549 to 2,350 mg/dl. The serum triglyceride level also decreased after taurine supplementation from 703 to 392 mg/dl. Although the HDL cholesterol level significantly decreased due to the high-cholesterol diet, it recovered to the control level fed a regular diet in response to taurine. Bile acid production was stimulated and hepatic cholesterol was reduced by taurine supplementation. A quantitative analysis using aortic cross-sections showed that areas of oil-red O positive lipid accumulation significantly decreased by 74% after taurine supplementation. These results demonstrated the lipid-lowering and anti-atherosclerotic effects of taurine in a diet-induced hyperlipidemic LAP quail model. The prevention of atherosclerosis by taurine is mainly attributed to an improvement in the serum cholesterol and triglyceride levels, which may be related to changes in the hepatic cholesterol metabolism. PMID:19229588

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

2010-01-01

337

Fire Suppression and Response  

NASA Technical Reports Server (NTRS)

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

Ruff, Gary A.

2004-01-01

338

CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice  

PubMed Central

Immune mechanisms are known to control the pathogenesis of atherosclerosis. However, the exact role of DCs, which are essential for priming of immune responses, remains elusive. We have shown here that the DC-derived chemokine CCL17 is present in advanced human and mouse atherosclerosis and that CCL17+ DCs accumulate in atherosclerotic lesions. In atherosclerosis-prone mice, Ccl17 deficiency entailed a reduction of atherosclerosis, which was dependent on Tregs. Expression of CCL17 by DCs limited the expansion of Tregs by restricting their maintenance and precipitated atherosclerosis in a mechanism conferred by T cells. Conversely, a blocking antibody specific for CCL17 expanded Tregs and reduced atheroprogression. Our data identify DC-derived CCL17 as a central regulator of Treg homeostasis, implicate DCs and their effector functions in atherogenesis, and suggest that CCL17 might be a target for vascular therapy. PMID:21633167

Weber, Christian; Meiler, Svenja; Döring, Yvonne; Koch, Miriam; Drechsler, Maik; Megens, Remco T.A.; Rowinska, Zuzanna; Bidzhekov, Kiril; Fecher, Caroline; Ribechini, Eliana; van Zandvoort, Marc A.M.J.; Binder, Christoph J.; Jelinek, Ivett; Hristov, Mihail; Boon, Louis; Jung, Steffen; Korn, Thomas; Lutz, Manfred B.; Förster, Irmgard; Zenke, Martin; Hieronymus, Thomas; Junt, Tobias; Zernecke, Alma

2011-01-01

339

Conjugated linoleic acid modulation of risk factors associated with atherosclerosis  

PubMed Central

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

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

2008-01-01

340

Leukotrienes in Atherosclerosis: New Target Insights and Future Therapy Perspectives  

PubMed Central

Atherosclerosis represents an important chronic inflammatory process associated with several pathophysiological reactions in the vascular wall. The arachidonic acid, released by phospholipase A2, is an important substrate for the production of a group of lipid mediators known as leukotrienes, which induce proinflammatory signaling through the activation of specific BLT and CysLT receptors. The interaction of these substances in the vascular wall determines important morphological alterations like the early lipid retention and the accumulation of foam cells, the development of intimal hyperplasia, and advanced atherosclerotic lesions, and it plays an important role in the rupture of atherosclerotic plaque. Many studies regarding myocardial ischemia and reperfusion show that leukotriene signaling may be involved in the development of ischemic injury. For these, reasons both leukotriene synthesis inhibitors and leukotriene receptor antagonists have been suggested for inducing beneficial effects at different stages of the atherosclerosis process and may represent a new therapeutic target in the treatment of atherosclerotic vessel diseases, in particular in acute coronary syndrome. PMID:20150962

Riccioni, Graziano; Zanasi, Alessandra; Vitulano, Nicola; Mancini, Barbara; D'Orazio, Nicolantonio

2009-01-01

341

Circle of Willis atherosclerosis, Alzheimer's disease and the Dean number.  

PubMed

The important role of atherosclerosis in pathophysiology of Alzheimer's Disease has become evident. Mechanisms such as hyperlipidemia, inflammation, abdominal obesity and insulin resistance are important yet they may not fully explain the specific involvement of the Circle of Willis in these pathologies. The Circle of Wills is a complex geometrical structure which has several areas with different curvature as well as various branching angles of vessels composing the circle. The hemodynamics in this region should take into account the Dean number which indicates the influence of curvature on the resistance to blood flow. Thus, areas with various curvature and angles may have different hemodynamics and there are certain areas in the Circle of Willis that are more likely to develop atherosclerotic changes. Therefore, this could suggest the novel pathophysiological pathway resulting from the geometric peculiarities of the Circle of Willis. One of the directions of future research is to examine whether specific areas of the Circle of Willis are more likely to develop atherosclerotic changes compared to other ones. Selective areas of the Circle of Willis affected by atherosclerotic changes could indicate the primary role of atherosclerosis promoting Alzheimer's disease although other pathophysiological mechanisms suggesting the opposite direction should be also examined in prospective studies. PMID:24198911

Ismailov, Rovshan M

2013-10-26

342

Zebrafish models of dyslipidemia: Relevance to atherosclerosis and angiogenesis  

PubMed Central

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

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

2013-01-01

343

Update on medical management of dyslipidemia and atherosclerosis.  

PubMed

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

Ginter, E; Simko, V

2013-01-01

344

Fish consumption and early atherosclerosis in middle-aged men.  

PubMed

To investigate the association between fish consumption and early atherosclerosis, we analyzed the relationship between fish consumption and average intima-media thickness (AveIMT) by carotid ultrasound in middle-aged Japanese men. Participants were 250 randomly selected, community-based Japanese men aged 40 to 49 years without a prior history of cardiovascular disease. AveIMT was calculated from the mean of 1-cm lengths of both the right and the left carotid arteries at 8 locations. A lifestyle survey was carried out using a self-administered questionnaire including the frequency of fish intake. There were 147 men in the fewer than 4 times per week fish consumption group and 103 men in the 4 or more times per week group. The mean AveIMT was significantly higher in the low fish consumption group than in the high fish consumption group (0.623+/-0.068 vs 0.605+/-0.065 mm, P=.03). After adjustment for age, waist circumference, pack-years of smoking, alcohol consumption, diabetes, and lipid-lowering medications, the significant difference in the AveIMT between the 2 groups remained. However, after further adjustment for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and C-reactive protein in the model, the significant difference disappeared. Fish consumption may be protective against early atherosclerosis in middle-aged men, probably through its beneficial effects on inflammation. PMID:17618950

Nakamura, Yasuyuki; Ueno, Yoshiki; Tamaki, Shinji; Kadowaki, Takashi; Okamura, Tomonori; Kita, Yoshikuni; Miyamatsu, Naomi; Sekikawa, Akira; Takamiya, Tomoko; El-Saed, Aiman; Sutton-Tyrrell, Kim; Ueshima, Hirotsugu

2007-08-01

345

Isoprostanes and other markers of peroxidation in atherosclerosis.  

PubMed

Several lines of evidence suggest that reactive oxygen species play a role in the development of vasculopathies, including those that define atherosclerosis, hypertension and restenosis after angioplasty. Confused picture emerging from prospective clinical trials of anti-oxidants may reflect inadequacy of traditional indices of lipid peroxidation in the recruitment of appropriate patients and in guiding the selection of the appropriate dose of anti-oxidant to be tested. Ex vivo indices of oxidant stress could have questionable veracity in assessing the actual rate of lipid peroxidation in vivo. The measurement of F(2)-isoprostanes (F(2)-iPs), formed non-enzimatically through free radical catalysed attack on esterified arachidonate, provides a reliable tool for identifying populations with enhanced rates of lipid peroxidation. Enhanced formation of F(2)-iPs, together with increased in vivo platelet activation, has been reported in association with several cardiovascular risk factors. Thus, it has been suggested that F(2)-iPs may transduce oxidant stress-dependent platelet activation. Measurements of 8-iso-PGF(2alpha), an abundant F(2)-iP formed in vivo, in urine may provide sensitive biochemical end-points for the assessment of the oxidant status of the patient and the true efficacy of anti-oxidant therapies. The incorporation of such biochemical end-points in clinical trials may help to verify the reliability of the oxidative modification hypothesis in the development of atherosclerosis. PMID:16298908

Patrignani, Paola; Tacconelli, Stefania

2005-11-01

346

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

PubMed

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

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

347

Differentially expressed genes in aortic smooth muscle cells from atherosclerosis-susceptible and atherosclerosis-resistant pigeons.  

PubMed

Susceptibility to spontaneous atherosclerosis in the White Carneau (WC-As) pigeon shows autosomal recessive inheritance. Aortic smooth muscle cells (SMC) cultured from susceptible WC-As and resistant Show Racer (SR-Ar) pigeons exhibit developmental and degenerative features corresponding to the respective SMC at atherosclerosis-prone sites in vivo. We used representational difference analysis to identify differentially expressed genes between WC-As and SR-Ar aortic SMC. Total RNA was extracted from cultured primary SMC of each breed, converted to double-stranded cDNA, followed by direct comparison in reciprocal representational difference analysis experiments. Difference products were cloned, sequenced, and identified by BLAST against the chicken genome. Six putative biochemical pathways were distinctly different between breeds with genes involved in energy metabolism and contractility exhibiting the most striking disparity. Genes associated with glycolysis and a synthetic SMC phenotype were expressed in WC-As cells. In contrast, SR-Ar cells expressed genes indicative of oxidative phosphorylation and a contractile SMC phenotype. In WC-As cells, the alternatives of insufficient ATP production limiting contractile function or the lack of functional contractile elements downregulating ATP synthesis cannot be distinguished due to the compressed in vitro versus in vivo developmental time frame. However, the genetic potential for effectively coupling energy production to muscle contraction present in the resistant SR-Ar was lacking in the susceptible WC-As. PMID:22582288

Anderson, J L; Taylor, R L; Smith, E C; Thomas, W K; Smith, S C

2012-06-01

348

Establishment and ultrasound characteristics of atherosclerosis in rhesus monkey  

PubMed Central

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

2015-01-01

349

Is there any relationship between Chlamydophila pneumoniae and coronary atherosclerosis among Iranians?  

PubMed Central

Background: Atherosclerosis is a coronary heart disease, andis the most common cause of death in the industrialized world. Some studies suggested that atherosclerosis may be triggered by infectious agents, mostly Chlamydophila pneumoniae. However, the role of C. pneumoniae in the pathogenesis of coronary atherosclerosis is still controversial. Objectives: This study was performed to evaluate whether there is a significant association between coronary artery atherosclerosis and C. pneumoniae by the polymerase chain reaction (PCR) method. Materials and Methods: This case-control study was carried out on formalin-fixed paraffin-embedded tissue biopsies of the coronary arteries obtained from 30 patients with coronary atherosclerosis and 30 subjects without atherosclerosis living in Northeast of Iran. All subjects' weight and height were determined, and the body mass index was calculated. We also reviewed the medical history and previous laboratory reports of patients. Deoxyribonucleic acid (DNA) was extracted, and C. pneumonia DNA was amplified and detected using PCR assay. Results: The age of the patients in the study group was from 18 to 50 years, and the male to female ratio was 5:1. Only oneout of the 30 coronary tissue samples had positive PCR for C. pneumoniae (3.3%), while it was negative for patients in the control group. Conclusions: This study showed that C. pneumoniae infection is not strongly associated with coronary artery atherosclerosis in Northeast of Iran. PMID:23661898

Sadeghian, Mohammad Hadi; Yazdi, Seyed Abbas Tabatabaee; Ayatollahi, Hossein; Keramati, Mohammad Reza; Ghazvini, Kiarash; Rezai, Ali Reza; Heidari, Nasrin; Sheikhi, Maryam; Shaghayegh, Gohar

2013-01-01

350

Up-regulated miR-93 contributes to coronary atherosclerosis pathogenesis through targeting ABCA1  

PubMed Central

Atherosclerosis is a chronic inflammatory disease, starting with the accumulation of white blood cells and fatty materials in the arterial wall. ABCA1, a gene promotes phospholipid and cholesterol transfer from cells to poorly lapidated ApoA1, is considered to be related to the pathogenesis of coronary atherosclerosis. Meanwhile, disturbed miRNAs were reported to be related to coronary atherosclerosis. To understand the relationship between miRNA, ABCA1 and coronary atherosclerosis pathogenesis, we first screened the miRNAs that may directly target 3’UTR of ABCA1 and miR-33a was used as positive control. Through dual luciferase assay and western blot, we confirmed that miR-93 and miR-17 repress ABCA1 expression through directly targeting 3’UTR. The serum miR-33a, miR-93 and miR-17 levels in participants were detected by qRT-PCR and a significant reduction of miR-33a and miR-93 was found in the coronary patients. After statistical analysis we identified that a negative correlation was existed in the serum miR-93 and ABCA1 levels in coronary atherosclerosis patients. Meanwhile, our results indicate that the serum miR-93 positively correlates with the serum cholesterol level. This research may give insight into understanding of coronary atherosclerosis pathogenesis and create an opportunity to the diagnosis of coronary atherosclerosis.

He, Yue; Lin, Lin; Cao, Jiaqi; Mao, Xudong; Qu, Yi; Xi, Beili

2015-01-01

351

Association of metabolic syndrome with coronary atherosclerosis in non-diabetic postmenopausal women.  

PubMed

Objective We investigated the possible association of metabolic syndrome with arterial stiffness and coronary atherosclerosis in non-diabetic, postmenopausal women. Methods A total of 293 non-diabetic, postmenopausal women who visited the health promotion center for a routine health check-up were included in a cross-sectional study. Arterial stiffness was measured by brachial-ankle pulse wave velocity, and coronary atherosclerosis was detected using 64-row multi-detector computed tomography. Results Women with coronary atherosclerosis had a significantly higher proportion of metabolic syndrome than those without coronary atherosclerosis. The brachial-ankle pulse wave velocity was significantly higher in women who had metabolic syndrome compared to those who had no metabolic syndrome (1567.71 ± 211.81 vs. 1336.75 ± 159.62 cm/s, p < 0.001). In addition, the brachial-ankle pulse wave velocity was shown to increase with increasing number of metabolic syndrome components (p for trend < 0.001). Metabolic syndrome was associated with increased risk of coronary atherosclerosis (adjusted odds ratio 2.38; 95% confidence interval 1.01-5.06), after adjusting for confounding factors. Conclusions Metabolic syndrome increases the risk of coronary atherosclerosis in postmenopausal women. Increased arterial stiffness may partly explain an increased risk of coronary atherosclerosis in postmenopausal women with metabolic syndrome. PMID:25233795

Yun, B H; Chon, S J; Lee, Y J; Han, E J; Cho, S; Choi, Y S; Lee, B S; Seo, S K

2015-04-01

352

Interleukin-10 protects against atherosclerosis by modulating multiple atherogenic macrophage function.  

PubMed

Atherosclerosis is primarily a disorder of lipid metabolism, but there is also a prominent chronic inflammatory component that drives the atherosclerotic lesion progression in the artery wall. During hyperlipidaemic conditions, there is a rapid influx of circulating monocytes into the atherosclerosis-prone areas of the arterial intima. These infiltrated monocytes differentiate into macrophages and take up the atherogenic lipoproteins in the intima of the vessel wall that have been modified within the lesion environment. Interleukin (IL)-10 is a prototypic anti-inflammatory cytokine made primarily by the macrophages and Th2 subtype T lymphocytes. In terms of atherosclerosis its major roles include inhibition of macrophage activation as well as inhibition of matrix metalloproteinase, pro-inflammatory cytokines and cyclooxygenase-2 expression in lipid-loaded and activated macrophage foam cells. Recent discoveries suggest another important role of IL-10 in atherosclerosis: its ability to alter lipid metabolism in macrophages. The current review will highlight the present knowledge on multiple ways in which IL-10 mediates atherosclerosis. As macrophages play a critical role in all stages of atherosclerosis, the review will concentrate on how IL-10 regulates the activities of macrophages that are especially important in the development of atherosclerosis. PMID:25373619

Han, X; Boisvert, W A

2015-03-01

353

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

PubMed Central

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

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

2012-01-01

354

Chlorogenic Acid Protects against Atherosclerosis in ApoE?/? Mice and Promotes Cholesterol Efflux from RAW264.7 Macrophages  

PubMed Central

Chlorogenic acid (CGA) is one of the most abundant polyphenols in the human diet and is suggested to be a potential antiatherosclerotic agent due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate the effect of CGA on atherosclerosis development in ApoE?/? mice and its potential mechanism. ApoE?/? mice were fed a cholesterol-rich diet without (control) or with CGA (200 and 400 mg/kg) or atorvastatin (4 mg/kg) for 12 weeks. During the study plasma lipid and inflammatory parameters were determined. Treatment with CGA (400 mg/kg) reduced atherosclerotic lesion area and vascular dilatation in the aortic root, comparable to atorvastatin. CGA (400 mg/kg) also significantly decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein-cholesterol as well as inflammatory markers. Supplementation with CGA or CGA metabolites-containing serum suppressed oxidized low-density lipoprotein (oxLDL)-induced lipid accumulation and stimulated cholesterol efflux from RAW264.7 cells. CGA significantly increased the mRNA levels of PPAR?, LXR?, ABCA1 and ABCG1 as well as the transcriptional activity of PPAR?. Cholesterol efflux assay showed that three major metabolites, caffeic, ferulic and gallic acids, significantly stimulated cholesterol efflux from RAW264.7 cells. These results suggest that CGA potently reduces atherosclerosis development in ApoE?/? mice and promotes cholesterol efflux from RAW264.7 macrophages. Caffeic, ferulic and gallic acids may be the potential active compounds accounting for the in vivo effect of CGA. PMID:25187964

Wu, Chongming; Luan, Hong; Zhang, Xue; Wang, Shuai; Zhang, Xiaopo; Sun, Xiaobo; Guo, Peng

2014-01-01

355

The assessment of cardiac autonomic functions in adolescents with a family history of premature atherosclerosis  

PubMed Central

OBJECTIVES: Subclinical atherosclerosis has been recently detected in adolescents with a family history of premature atherosclerosis. However, no studies in the literature have assessed the cardiac autonomic functions of these adolescents. The aim of this study was to evaluate the cardiac autonomic functions of adolescents with a family history of premature atherosclerosis compared with those of age- and gender-matched adolescents without a family history of atherosclerosis. METHOD: We evaluated the cardiac autonomic functions of 36 adolescents with a family history of premature atherosclerosis (Group 1) and compared them with those of 31 age- and gender-matched adolescents whose parents did not have premature atherosclerosis (Group 2). Twenty-four-hour time domain (standard deviation of all normal sinus RR intervals [SDNN], standard deviation of the mean of normal RR intervals in each 5-minute segment [SDANN], root-mean-square differences in successive RR intervals) and frequency domain (very low frequency, low frequency, high frequency, low frequency/high frequency) parameters of heart rate variability were used for the evaluation of cardiac autonomic functions. RESULTS: There were no differences in the time and frequency domain parameters of heart rate variability between the two groups. Heart rate was negatively correlated with SDNN (r?=?-0.278, p?=?0.035), while age was significantly correlated with root-mean-square differences in successive RR intervals, high frequency, low frequency and low frequency/high frequency (r?=?-0.264, -0.370, 0.265 and 0.374, respectively; p<0.05 for all). CONCLUSION: We found that the cardiac autonomic functions of adolescents with a family history of premature atherosclerosis were not different compared with those of adolescents without a positive family history of premature atherosclerosis. It appears that subclinical atherosclerosis does not reach a critical value such that it can alter cardiac autonomic functions in adolescence. PMID:25627994

Dursun, Huseyin; Kilicaslan, Baris; Aydin, Mehmet

2014-01-01

356

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

PubMed Central

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

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

357

Clinical features of radiation-induced carotid atherosclerosis.  

PubMed

Carotid arteries frequently receive significant incidental doses of radiation during the treatment of malignant diseases, including head and neck cancer, breast cancer and lymphoma. Vascular injury after treatment may result in carotid artery stenosis and increased risk of neurological sequelae, such as stroke and transient ischaemic attack. The long latent interval from treatment to the development of clinical complications makes investigation of this process difficult, particularly in regard to the design of interventional clinical studies. Nevertheless, there is compelling clinical evidence that radiation contributes to carotid atherosclerosis. This overview examines the effect of radiotherapy on the carotid arteries, the underlying pathological processes and their clinical manifestations. The use of serum biomarkers in risk-prediction models and the potential value of new imaging techniques as tools for defining earlier surrogate end points will also be discussed. PMID:24188597

Gujral, D M; Shah, B N; Chahal, N S; Senior, R; Harrington, K J; Nutting, C M

2014-02-01

358

Dynamic Aspects of Macrophage Polarization during Atherosclerosis Progression and Regression  

PubMed Central

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

Peled, Michael; Fisher, Edward A.

2014-01-01

359

Cathepsins and cystatin C in atherosclerosis and obesity.  

PubMed

Given the increasing prevalence of human obesity worldwide, there is an urgent need for a better understanding of the molecular mechanisms linking obesity to metabolic and cardiovascular diseases. Our knowledge is nevertheless limited regarding molecules linking adipose tissue to downstream complications. The importance of cathepsins was brought to light in this context. Through a large scale transcriptomic analysis, our group recently identified the gene encoding cathepsin S as one of the most deregulated gene in the adipose tissue of obese subjects and positively correlated with body mass index. Other members of the cathepsin family are expressed in the adipose tissue, including cathepsin K and cathepsin L. Given their implication in atherogenesis, these proteases could participate into the well established deleterious relationship between enlarged adipose tissue and increased cardiovascular risk. Here, we review the clinical and experimental evidence relevant to the role of cathepsins K, L and S and their most abundant endogenous inhibitor, cystatin C, in atherosclerosis and in obesity. PMID:20417681

Lafarge, Jean-Charles; Naour, Nadia; Clément, Karine; Guerre-Millo, Michèle

2010-11-01

360

Mechanisms of Premature Atherosclerosis in Rheumatoid Arthritis and Lupus  

PubMed Central

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

Kahlenberg, J. Michelle; Kaplan, Mariana J.

2014-01-01

361

The Downstream Regulation of Chemokine Receptor Signalling: Implications for Atherosclerosis  

PubMed Central

Heterotrimeric G-protein-coupled receptors (GPCRs) are key mediators of intracellular signalling, control numerous physiological processes, and are one of the largest class of proteins to be pharmacologically targeted. Chemokine-induced macrophage recruitment into the vascular wall is an early pathological event in the progression of atherosclerosis. Leukocyte activation and chemotaxis during cell recruitment are mediated by chemokine ligation of multiple GPCRs. Regulation of GPCR signalling is critical in limiting vascular inflammation and involves interaction with downstream proteins such as GPCR kinases (GRKs), arrestin proteins and regulator of G-protein signalling (RGS) proteins. These have emerged as new mediators of atherogenesis by functioning in internalisation, desensitisation, and signal termination of chemokine receptors. Targeting chemokine signalling through these proteins may provide new strategies to alter atherosclerotic plaque formation and plaque biology. PMID:23690662

Channon, Keith M.

2013-01-01

362

Soluble TWEAK independently predicts atherosclerosis in renal transplant patients  

PubMed Central

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

2013-01-01

363

Chapter 2. Atherosclerosis of the aorta in five towns  

PubMed Central

Fatty streak was always present in both the thoracic aorta and the abdominal aorta in the youngest subjects studied (aged 10-14 years). Fibrous plaque was present in a small proportion of these young subjects, but a rapid increase in prevalence occurred as early as the fourth decade. Complicated and calcified lesions appeared as early as the age of 20-25 years but a rapid increase in prevalence was seen after age 40 for complicated lesions and after age 50 for calcified lesions. There were differences in the prevalence of severe lesions among the five towns. There was little increase in the extent of atherosclerosis in the thoracic aorta before the age of 40 and in the abdominal aorta before the age of 20. The increase was more rapid after those ages. When atherosclerosis had affected about 50% of the intimal surface of the thoracic aorta and 70% of the intimal surface of the abdominal aorta, the increase slowed down considerably. In contrast to other types of lesion, the extent of fatty streak increased only up to 30 years of age, when it occupied 25-30% of the intimal surface. Then it declined and in the older age groups did not exceed 4-5% in men or women. The extent of fibrous plaque and complicated lesions was at all ages greater in men than in women, while the extent of fatty streak and calcified lesions in older age groups was greater in women. There were marked differences in the extent of atherosclerotic lesions in the five towns. PMID:1087188

Vihert, A. M.

1976-01-01

364

Subclinical atherosclerosis measures for cardiovascular prediction in CKD.  

PubMed

Whether inclusion of the coronary artery calcium score improves cardiovascular risk prediction in individuals with CKD, a population with unique calcium-phosphate homeostasis, is unknown. Among 6553 participants ages 45-84 years without prior cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, coronary artery calcium score was assessed for cardiovascular risk prediction beyond the Framingham predictors in those with (n=1284) and without CKD and contrasted with carotid intima-media thickness and ankle-brachial index (two other measures of subclinical atherosclerosis). During a median follow-up of 8.4 years, 650 cardiovascular events (coronary heart disease, stroke, heart failure, and peripheral artery disease) occurred (236 events in subjects with CKD). In Cox proportional hazards models adjusted for Framingham predictors, each subclinical measure was independently associated with cardiovascular outcomes, with larger adjusted hazard ratios (HRs; per 1 SD) for coronary artery calcium score than carotid intima-media thickness or ankle-brachial index in subjects without and with CKD (HR, 1.69; 95% confidence interval [95% CI], 1.45 to 1.97 versus HR, 1.12; 95% CI, 1.00 to 1.25 and HR, 1.20; 95% CI, 1.08 to 1.32, respectively). Compared with inclusion of carotid intima-media thickness or ankle-brachial index, inclusion of the coronary artery calcium score led to greater increases in C statistic for predicting cardiovascular disease and net reclassification improvement. Coronary artery calcium score performed best for the prediction of coronary heart disease and heart failure, regardless of CKD status. In conclusion, each measure improved cardiovascular risk prediction in subjects with CKD, with the greatest improvement observed with coronary artery calcium score. PMID:25145930

Matsushita, Kunihiro; Sang, Yingying; Ballew, Shoshana H; Shlipak, Michael; Katz, Ronit; Rosas, Sylvia E; Peralta, Carmen A; Woodward, Mark; Kramer, Holly J; Jacobs, David R; Sarnak, Mark J; Coresh, Josef

2015-02-01

365

ApoE controls the interface linking lipids and inflammation in atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory disease of the arterial walls that often leads to myocardial infarction and/or stroke. Hypercholesterolemia and an imbalance of peripheral leukocyte counts, leading to arterial leukocyte infiltration, are considered independent risk factors for atherosclerosis. However, in this issue of the JCI, Murphy and colleagues identify a mechanistic link between hypercholesterolemia, leukocytosis, and the subsequent development of atherosclerotic lesions in mice. These findings could pave the way for the development of novel treatment strategies to control leukocyte homeostasis and atherosclerosis. PMID:21968109

Weber, Christian; Soehnlein, Oliver

2011-01-01

366

Therapeutic implications of chemokine-mediated pathways in atherosclerosis: realistic perspectives and utopias.  

PubMed

Current perspectives on the pathogenesis of atherosclerosis strongly support the involvement of inflammatory mediators in the establishment and progression of atherosclerostic lesions. Chemokine-mediated mechanisms are potent regulators of such processes by orchestrating the interactions of inflammatory cellular components of the peripheral blood with cellular components of the arterial wall. The increasing evidence supporting the role of chemokine pathways in atherosclerosis renders chemokine ligands and their receptors potential therapeutic targets. In the following review, we aim to highlight the special structural and functional features of chemokines and their receptors in respect to their roles in atherosclerosis, and examine to what extent available data can be applied in disease management practices. PMID:20711227

Apostolakis, Stavros; Amanatidou, Virginia; Spandidos, Demetrios A

2010-09-01

367

Therapeutic implications of chemokine-mediated pathways in atherosclerosis: realistic perspectives and utopias  

PubMed Central

Current perspectives on the pathogenesis of atherosclerosis strongly support the involvement of inflammatory mediators in the establishment and progression of atherosclerostic lesions. Chemokine-mediated mechanisms are potent regulators of such processes by orchestrating the interactions of inflammatory cellular components of the peripheral blood with cellular components of the arterial wall. The increasing evidence supporting the role of chemokine pathways in atherosclerosis renders chemokine ligands and their receptors potential therapeutic targets. In the following review, we aim to highlight the special structural and functional features of chemokines and their receptors in respect to their roles in atherosclerosis, and examine to what extent available data can be applied in disease management practices. PMID:20711227

Apostolakis, Stavros; Amanatidou, Virginia; Spandidos, Demetrios A

2010-01-01

368

A historical perspective towards a non-invasive treatment for patients with atherosclerosis  

PubMed Central

The history of atherosclerosis and cardiovascular disease dates back to ancient times. From the teachings of Galen to the response-to-injury hypothesis of Russel Ross, we have now arrived at the concept of the vulnerable plaque. Next to the development of new treatment options for patients with atherosclerosis, also novel diagnostic imaging techniques have been developed to visualise the arterial wall and to characterise plaque composition. In this article the historical context of atherosclerosis and the attempts towards a noninvasive therapy for patients with atherosclerotic diseases are described. (Neth Heart J 2009;17:140-4.19421359) PMID:19421359

Slijkhuis, W.; Mali, W.; Appelman, Y.

2009-01-01

369

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

SciTech Connect

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

Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China)] [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China) [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China) [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China)] [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China) [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China)] [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China)] [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)] [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

2011-08-15

370

New aspects on the metabolic role of intestinal microbiota in the development of atherosclerosis.  

PubMed

Gut microbiota remains a very interesting, yet largely unexplored ecosystem inside the human organism. The importance of this ecosystem for the physiology and the pathophysiology of the organism is being slowly unraveled. Recent studies reveal a connection between intestinal microbiota and atherosclerosis development. It seems that alterations in the function and composition of this bacterial population lead through complex mechanisms to a high risk for atherosclerosis. Although these mechanisms remain largely unknown, published studies show that microbiota can lead to atherosclerosis either by augmenting known risk factors or via other, more "direct" mechanisms. This review article summarizes the available literature regarding this matter. PMID:25676802

Drosos, Ioannis; Tavridou, Anna; Kolios, George

2015-04-01

371

Associations of cardiovascular disease risk factors and calcified atherosclerosis with aortoiliac bifurcation position: the multiethnic study of atherosclerosis.  

PubMed

We investigated associations of cardiovascular disease (CVD) risk factors and calcified atherosclerosis with aortoiliac bifurcation position. The bifurcation position was determined by measuring the distance from the aortoiliac bifurcation to the L5-S1 disk space (or aortoiliac bifurcation distance [AIBD]), using computed tomography scans. The 1711 study participants (51% male) had a mean age of 62 ± 10 years and a mean AIBD of 26 ± 15 mm. In multivariable linear regression, older age, male gender, smoking, hypertension, larger aortic diameter, and smaller lumbar height were each independently associated with a smaller AIBD (more caudal bifurcation position). In contrast, diabetes, elevated triglycerides, and increased pulse pressure were independently associated with a larger AIBD (more cephalad bifurcation position). These findings suggest that age-related bifurcation descent is associated with CVD markers for aortic disease. Future studies should assess whether the bifurcation position is an independent prognosticator for CVD. PMID:24375634

Forbang, Nketi I; Ix, Joachim H; Allison, Matthew A; Criqui, Michael H

2015-01-01

372

Growth hormone suppression test  

MedlinePLUS

... level of GH, a condition that leads to gigantism in children and acromegaly in adults. It is ... during the suppression test, the doctor will suspect gigantism or acromegaly. You may need to be retested ...

373

Understanding the Role of B cells in Atherosclerosis: Potential Clinical Implications  

PubMed Central

Atherosclerosis is a progressive inflammatory disease of the medium to large arteries that is the largest contributor to cardiovascular disease (CVD). 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 cardivascular disease and the immune system between mice and humans, making the case for greater efforts at addressing the role of B cells in humans atherosclerosis. PMID:24308836

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

2015-01-01

374

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

PubMed Central

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

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

2014-01-01

375

Genetic network identifies novel pathways contributing to atherosclerosis susceptibility in the innominate artery  

PubMed Central

Background Atherosclerosis, the underlying cause of cardiovascular disease, results from both genetic and environmental factors. Methods In the current study we take a systems-based approach using weighted gene co-expression analysis to identify a candidate pathway of genes related to atherosclerosis. Bioinformatic analyses are performed to identify candidate genes and interactions and several novel genes are characterized using in-vitro studies. Results We identify 1 coexpression module associated with innominate artery atherosclerosis that is also enriched for inflammatory and macrophage gene signatures. Using a series of bioinformatics analysis, we further prioritize the genes in this pathway and identify Cd44 as a critical mediator of the atherosclerosis. We validate our predictions generated by the network analysis using Cd44 knockout mice. Conclusion These results indicate that alterations in Cd44 expression mediate inflammation through a complex transcriptional network involving a number of previously uncharacterized genes. PMID:25115202

2014-01-01

376

Atherosclerosis and myocardial bridging: Not a benign combination. An autopsy case report  

PubMed Central

Myocardial bridging is a congenital coronary anomaly with a variety of clinical manifestations. Traditionally, myocardial bridging has been considered a benign condition, but some cases of myocardial ischemia, infarction and sudden cardiac death due to myocardial bridging have been reported. Various studies have suggested that in their intramyocardial segments, these vessels are protected from obstructive atherosclerosis, with atherosclerosis being present in the proximal part of the artery. We report a case in a 45-year-old male who had a 2.5-cm long myocardial bridging over the left anterior descending artery, with obstructive atherosclerosis being present in the proximal as well as the intramyocardial part (part of the artery below the myocardial bridge). Atherosclerosis occurring in the intramyocardial segment is a rare occurrence, and combined with systolic narrowing by the myocardial bridge can lead to ischemia of the cardiac musculature. PMID:22629044

Thej, M. J.; Kalyani, R.; Kiran, J.

2012-01-01

377

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

E-print Network

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...

Wamil, Ma?gorzata

2009-01-01

378

Chapter 14. Atherosclerosis of the aorta and coronary arteries in coronary heart disease  

PubMed Central

Aortic and coronary atherosclerosis and the prevalence of coronary stenosis and thrombosis were studied in subjects who had died of fresh or recurrent myocardial infarction or had suffered from myocardial infarction in the past. In general, severe atherosclerosis of the coronary arteries with stenosis and calcification was almost a prerequisite for the development of coronary heart disease. The frequency of coronary heart disease varied widely both in different countries and in different towns in the same country. Considerable variations were found among the various towns in the frequency of stenosis and thrombosis in those who had died of coronary heart disease. This finding indicates that although atherosclerosis is indeed a prerequisite for the development of myocardial infarction, other factors may play a significant role in its occurrence. The weight of the heart in persons (excluding hypertensives) with coronary stenosis or a first fresh myocardial infarction was considerably greater than that in the low atherosclerosis group. PMID:1087200

Vihert, A. M.

1976-01-01

379

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

E-print Network

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

Lediju, Muyinatu A. (Muyinatu Adebisi)

2006-01-01

380

The Involvement of NFAT Transcriptional Activity Suppression in SIRT1-Mediated Inhibition of COX-2 Expression Induced by PMA/Ionomycin  

PubMed Central

SIRT1, a class III histone deacetylase, acts as a negative regulator for many transcription factors, and plays protective roles in inflammation and atherosclerosis. Transcription factor nuclear factor of activated T cells (NFAT) has been previously shown to play pro-inflammatory roles in endothelial cells. Inhibition of NFAT signaling may be an attractive target to regulate inflammation in atherosclerosis. However, whether NFAT transcriptional activity is suppressed by SIRT1 remains unknown. In this study, we found that SIRT1 suppressed NFAT-mediated transcriptional activity. SIRT1 interacted with NFAT, and the NHR and RHR domains of NFAT mediated the interaction with SIRT1. Moreover, we found that SIRT1 primarily deacetylated NFATc3. Adenoviral over-expression of SIRT1 suppressed PMA and calcium ionophore Ionomycin (PMA/Io)-induced COX-2 expression in human umbilical vein endothelial cells (HUVECs), while SIRT1 RNAi reversed the effects in HUVECs. Moreover, inhibition of COX-2 expression by SIRT1 in PMA/Io-treated HUVECs was largely abrogated by inhibiting NFAT activation. Furthermore, SIRT1 inhibited NFAT-induced COX-2 promoter activity, and reduced NFAT binding to the COX-2 promoter in PMA/Io-treated HUVECs. These results suggest that suppression of NFAT transcriptional activity is involved in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Io, and that the negative regulatory mechanisms of NFAT by SIRT1 may contribute to its anti-inflammatory effects in atherosclerosis. PMID:24859347

Huang, Yue; Liu, Guang; Gao, Peng; Wan, Yan-Zhen; Zhang, Ran; Zhang, Zhu-Qin; Yang, Rui-Feng; Tang, Xiaoqiang; Xu, Jing; Wang, Xu; Chen, Hou-Zao; Liu, De-Pei

2014-01-01

381

Atherosclerosis Pathophysiology and the Role of Novel Risk Factors: A Clinicobiochemical Perspective  

Microsoft Academic Search

Atherosclerosis is the root cause of the biggest killer of the 21st century. Mechanisms contributing to atherogenesis are multiple and complex. A number of theories—including the role of dyslipidemia, hypercoagulability, oxidative stress, endothelial dysfunction, and inflammation and infection by certain pathogens—have been propounded from time to time explain this complex phenomenon. Recently it has been suggested that atherosclerosis is a

V. Mallika; Binita Goswami; Medha Rajappa

2007-01-01

382

Immunohistochemical localization of subtilisin\\/kexin-like proprotein convertases in human atherosclerosis  

Microsoft Academic Search

Integrins are heterodimeric a\\/ß receptors that link the cytoskeleton with the extracellular matrix, thereby regulating several cell functions important in atherosclerosis. In vitro, the subtilisin\\/kexin-like proprotein convertases (PCs), namely PC5 and furin, have been shown to be responsible for the endoproteolytic activation of the av integrin subunit. Based on their cleavage activity, these PCs are potential targets in atherosclerosis. In

Philipp Stawowy; Heike Kallisch; Núbia Borges Pereira Stawowy; Dietger Stibenz; John P. Veinot; Michael Gräfe; Nabil G. Seidah; Michel Chrétien; Eckart Fleck; Kristof Graf

2005-01-01

383

Porphyromonas gingivalis mediated periodontal disease and atherosclerosis: disparate diseases with commonalities in pathogenesis through TLRs.  

PubMed

Toll-like receptors (TLRs) are a group of pathogen-associated molecular pattern receptors, which play an important role in innate immune signaling in response to microbial infection. It has been demonstrated that TLRs are differentially up regulated in response to microbial infection and chronic inflammatory diseases such as atherosclerosis. Furthermore hyperlipidemic mice deficient in TLR2, TLR4, and MyD88 signaling exhibit diminished inflammatory responses and decreased atherosclerosis. Accumulating evidence has implicated specific infectious agents including the periodontal disease pathogen Porphyromonas gingivalis in the progression of atherosclerosis. Evidence in humans suggesting that periodontal infection predisposes to atherosclerosis is derived from studies demonstrating that the periodontal pathogen P. gingivalis resides in the wall of atherosclerotic vessels and seroepidemiological studies demonstrating an association between pathogen-specific IgG antibodies and atherosclerosis. We have established that the inflammatory signaling pathways that P. gingivalis utilizes is dependent on the cell type and this specificity clearly influences innate immune signaling in the context of local and distant chronic inflammation induced by this pathogen. We have demonstrated that P. gingivalis requires TLR2 to induce oral inflammatory bone lose in mice. Furthermore, we have demonstrated that P. gingivalis infection accelerates atherosclerosis in hyperlipidemic mice with an associated increase in expression of TLR2 and TLR4 in atherosclerotic lesions. Our recent work with P. gingivalis has demonstrated the effectiveness of specific intervention strategies (immunization) in the prevention of pathogen-accelerated atherosclerosis. Improved understanding of the mechanisms driving infection, and chronic inflammation during atherosclerosis may ultimately provide new targets for therapy. PMID:18220804

Gibson, Frank C; Genco, Caroline A

2007-01-01

384

Levels of soluble adhesion molecules in various clinical presentations of coronary atherosclerosis  

Microsoft Academic Search

Adhesion molecules play an important role in the development and course of coronary atherosclerosis. In this study, soluble forms of vascular cell adhesion molecule (VCAM-1) intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin were evaluated in patients with various clinical presentations of coronary atherosclerosis and compared them to those with angiographically documented normal coronary arteries. Venous plasma samples were collected from

Ümit Güray; A. Riza Erbay; Yesim Güray; M. Birhan Yilmaz; Asiye Ayca Boyac?; Hatice Sasmaz; Sule Korkmaz; Emine Kütük

2004-01-01

385

A perspective for atherosclerosis vaccination: is there a place for plant-based vaccines?  

PubMed

Alternatives to pharmacological treatments for atherosclerosis are highly desirable in terms of cost and compliance. During the last two decades several vaccination strategies have been reported as an effort to develop immunotherapeutic treatments. This approach consists on eliciting immune responses able to modulate either the atherosclerosis-associated inflammatory processes or the activity of some physiological mechanisms that are up-regulated under this pathologic condition. In particular, the apolipoprotein B100 (ApoB100) and the cholesterilester transferase protein (CETP) have been targeted in these strategies. It is considered that recent progress in the development of experimental models of oral vaccines against atherosclerosis has opened a new avenue in the field: as plant-based vaccines are considered a viable platform for vaccine production and delivery at low costs, they could serve as an oral-delivered therapeutic approach for atherosclerosis in an economical and patient-friendly manner. The rationale of the design, development and evaluation of possible plant-based vaccines against atherosclerosis is discussed in this review. We identify within this approach a significant trend that will positively impact the field of atherosclerosis vaccination. PMID:23313656

Salazar-González, Jorge Alberto; Rosales-Mendoza, Sergio

2013-02-27

386

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

PubMed Central

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

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

2014-01-01

387

Tetrahydrobiopterin Deficiency and Nitric Oxide Synthase Uncoupling Contribute to Atherosclerosis Induced by Disturbed Flow  

PubMed Central

Objective Tetrahydrobiopterin (BH4) is a critical cofactor for Nitric Oxide (NO) synthesis by NO synthase (NOS). Recently, we demonstrated that disturbed flow produced by partial carotid ligation decreases BH4 levels in vivo. We therefore aimed to determine whether atherosclerosis induced by disturbed flow is due to BH4 deficiency and NOS uncoupling and whether increasing BH4 would prevent endothelial dysfunction, plaque inflammation and atherosclerosis. Methods and Results We produced a region of disturbed flow in ApoE?/? mice using partial carotid ligation and fed these animals a high-fat diet. This caused eNOS uncoupling as characterized by increased vascular superoxide production, altered vascular reactivity and a change in eNOS migration on low-temperature gel. These perturbations were accompanied by severe atherosclerosis, infiltration of T cells and macrophages, and an increase in cytokine production. Treatment with BH4 recoupled NOS, decreased superoxide production, imporoved endothelium-dependent vasodilatation and virtually eliminated atherosclerosis. BH4 treatment also markedly reduced vascular inflammation and improved the cytokine milieu induced by disturbed flow. Conclusions Our results highlight a key role of BH4 deficiency and NOS uncoupling in atherosclerosis induced by disturbed flow, and provide insight into the effect of modulating vascular BH4 levels on atherosclerosis and inflammation at these sites of the circulation. PMID:21512164

Li, Li; Chen, Wei; Rezvan, Amir; Jo, Hanjoong; Harrison, David G.

2011-01-01

388

Depletion of FOXP3+ regulatory T cells promotes hypercholesterolemia and atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory disease promoted by hyperlipidemia. Several studies support FOXP3-positive regulatory T cells (Tregs) as inhibitors of atherosclerosis; however, the mechanism underlying this protection remains elusive. To define the role of FOXP3-expressing Tregs in atherosclerosis, we used the DEREG mouse, which expresses the diphtheria toxin (DT) receptor under control of the Treg-specific Foxp3 promoter, allowing for specific ablation of FOXP3+ Tregs. Lethally irradiated, atherosclerosis-prone, low-density lipoprotein receptor–deficient (Ldlr–/–) mice received DEREG bone marrow and were injected with DT to eliminate FOXP3+ Tregs. Depletion of Tregs caused a 2.1-fold increase in atherosclerosis without a concomitant increase in vascular inflammation. These mice also exhibited a 1.7-fold increase in plasma cholesterol and an atherogenic lipoprotein profile with increased levels of VLDL. Clearance of VLDL and chylomicron remnants was hampered, leading to accumulation of cholesterol-rich particles in the circulation. Functional and protein analyses complemented by gene expression array identified reduced protein expression of sortilin-1 in liver and increased plasma enzyme activity of lipoprotein lipase, hepatic lipase, and phospholipid transfer protein as mediators of the altered lipid phenotype. These results demonstrate that FOXP3+ Tregs inhibit atherosclerosis by modulating lipoprotein metabolism. PMID:23426179

Klingenberg, Roland; Gerdes, Norbert; Badeau, Robert M.; Gisterå, Anton; Strodthoff, Daniela; Ketelhuth, Daniel F.J.; Lundberg, Anna M.; Rudling, Mats; Nilsson, Stefan K.; Olivecrona, Gunilla; Zoller, Stefan; Lohmann, Christine; Lüscher, Thomas F.; Jauhiainen, Matti; Sparwasser, Tim; Hansson, Göran K.

2013-01-01

389

Depletion of FOXP3+ regulatory T cells promotes hypercholesterolemia and atherosclerosis.  

PubMed

Atherosclerosis is a chronic inflammatory disease promoted by hyperlipidemia. Several studies support FOXP3-positive regulatory T cells (Tregs) as inhibitors of atherosclerosis; however, the mechanism underlying this protection remains elusive. To define the role of FOXP3-expressing Tregs in atherosclerosis, we used the DEREG mouse, which expresses the diphtheria toxin (DT) receptor under control of the Treg-specific Foxp3 promoter, allowing for specific ablation of FOXP3+ Tregs. Lethally irradiated, atherosclerosis-prone, low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice received DEREG bone marrow and were injected with DT to eliminate FOXP3(+) Tregs. Depletion of Tregs caused a 2.1-fold increase in atherosclerosis without a concomitant increase in vascular inflammation. These mice also exhibited a 1.7-fold increase in plasma cholesterol and an atherogenic lipoprotein profile with increased levels of VLDL. Clearance of VLDL and chylomicron remnants was hampered, leading to accumulation of cholesterol-rich particles in the circulation. Functional and protein analyses complemented by gene expression array identified reduced protein expression of sortilin-1 in liver and increased plasma enzyme activity of lipoprotein lipase, hepatic lipase, and phospholipid transfer protein as mediators of the altered lipid phenotype. These results demonstrate that FOXP3(+) Tregs inhibit atherosclerosis by modulating lipoprotein metabolism. PMID:23426179

Klingenberg, Roland; Gerdes, Norbert; Badeau, Robert M; Gisterå, Anton; Strodthoff, Daniela; Ketelhuth, Daniel F J; Lundberg, Anna M; Rudling, Mats; Nilsson, Stefan K; Olivecrona, Gunilla; Zoller, Stefan; Lohmann, Christine; Lüscher, Thomas F; Jauhiainen, Matti; Sparwasser, Tim; Hansson, Göran K

2013-03-01

390

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

PubMed

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

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

2013-01-01

391

The Role of Oxidized Low-Density Lipoproteins in Atherosclerosis: The Myths and the Facts  

PubMed Central

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

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

2013-01-01

392

Decreased bone mineral density is associated with coronary atherosclerosis in healthy postmenopausal women  

PubMed Central

Objective This study aimed to assess the association between bone mineral density (BMD) and coronary atherosclerosis in healthy postmenopausal women. Methods We performed a retrospective review of 252 postmenopausal women who had visited a health promotion center for a routine checkup. BMD of the lumbar spine (L1-L4) and femoral neck was evaluated using dual-energy X-ray absorptiometry, and coronary atherosclerosis was assessed using 64-row multidetector computed tomography. Participants were divided into normal BMD and osteopenia-osteoporosis groups, according to the T-scores of their lumbar spine or femoral neck. Results Participants with osteopenia-osteoporosis had a significantly higher proportion of coronary atherosclerosis than did those with normal BMD at the lumbar spine (P=0.003) and femoral neck (P=0.004). Osteopenia-osteoporosis at the lumbar spine (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.12 to 7.27) or femoral neck (OR, 3.35; 95% CI, 1.07 to 10.57) was associated with coronary atherosclerosis, after controlling for age and cardiovascular risk factors. Conclusion Decreased BMD is associated with coronary atherosclerosis in healthy postmenopausal women, independent of age and cardiovascular risk factors. Postmenopausal women with decreased BMD may have a higher risk of developing coronary atherosclerosis. PMID:25798428

Seo, Seok Kyo; Yun, Bo Hyon; Noe, Eun Bee; Suh, Jong Wook; Choi, Young Sik

2015-01-01

393

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

PubMed Central

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

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

394

mTOR enhances foam cell formation by suppressing the autophagy pathway.  

PubMed

Recently, autophagy has drawn more attention in cardiovascular disease as it has important roles in lipid metabolism. Mammalian target of rapamycin (mTOR) is a key regulator of autophagy; however, its effect on atherosclerosis and the underlying mechanism remains undefined. In this study, an obvious upregulation of mTOR and p-mTOR protein was observed in macrophage-derived foam cells. Blocking mTOR expression with specific small interference RNA (siRNA) dramatically suppressed foam cell formation, accompanied by a decrease of lipid deposition. Further mechanistic analysis indicated that suppressing mTOR expression significantly upregulated autophagic marker LC3 expression and downregulated autophagy substrate p62 levels, indicating that mTOR silencing triggered autophagosome formation. Moreover, blocking mTOR expression obviously accelerated neutral lipid delivery to lysosome and cholesterol efflux from foam cells, implying that mTOR could induce macrophage foam cell formation by suppressing autophagic pathway. Further, mTOR silencing significantly upregulated ULK1 expression, which was accounted for mTOR-induced foam cell formation via autophagic pathway as treatment with ULK1 siRNA dampened LC3-II levels and increased p62 expression, concomitant with lipid accumulation and decreased cholesterol efflux from foam cells. Together, our data provide an insight into how mTOR accelerates the pathological process of atherosclerosis. Accordingly, blocking mTOR levels may be a promising therapeutic agent against atherosclerotic complications. PMID:24512183

Wang, Xiaochuang; Li, Lingxia; Niu, Xiaolin; Dang, Xiaoyan; Li, Ping; Qu, Li; Bi, Xiaoju; Gao, Yanxia; Hu, Yanfen; Li, Manxiang; Qiao, Wanhai; Peng, Zhuo; Pan, Longfei

2014-04-01

395

Common carotid arterial interadventitial distance (diameter) as an indicator of the damaging effects of age and atherosclerosis, a cross-sectional study of the Atherosclerosis Risk in Community Cohort Limited Access Data (ARICLAD), 1987–89  

Microsoft Academic Search

BACKGROUND: The effect of age on common carotid artery diameter is unclear for varying atherosclerosis risk levels. METHODS: Cross-sectional data from the Atherosclerosis Risk in Communities Limited Access Data set were used to estimate the association of age with B-mode ultrasound common carotid artery diameter for three atherosclerosis risk levels. Based on information from clinical examinations, B-mode ultrasounds, questionnaires, blood

Marsha L Eigenbrodt; Zoran Bursac; Kathryn M Rose; David J Couper; Richard E Tracy; Gregory W Evans; Frederick L Brancati; Jawahar L Mehta

2006-01-01

396

Explosion suppression system  

DOEpatents

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

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

1992-01-01

397

Potential contributions of intimal and plaque hypoxia to atherosclerosis.  

PubMed

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

Fong, Guo-Hua

2015-06-01

398

Vascular health late after Kawasaki disease: implications for accelerated atherosclerosis  

PubMed Central

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

2014-01-01

399

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

PubMed

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

Cheung, Yiu-Fai

2014-11-01

400

HDL-Mimetic PLGA Nanoparticle To Target Atherosclerosis Plaque Macrophages.  

PubMed

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

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

401

Oxidative stress and early atherosclerosis: novel antioxidant treatment.  

PubMed

Atherosclerotic lesions initiate in regions characterized by low shear stress and reduced activity of endothelial atheroprotective molecules such as nitric oxide, which is the key molecule managing vascular homeostasis. The generation of reactive oxygen species from the vascular endothelium is strongly related to various enzymes, such as xanthine oxidase, endothelial nitric oxide synthase and nicotinamide-adenine dinucleotide phosphate oxidase. Several pharmaceutical agents, including angiotensin converting enzyme inhibitors, angiotensin receptors blockers and statins, along with a variety of other agents, have demonstrated additional antioxidant properties beyond their principal role. Reports regarding the antioxidant role of vitamins present controversial results, especially those based on large scale studies. In addition, there is growing interest on the role of dietary flavonoids and their potential to improve endothelial function by modifying the oxidative stress status. However, the vascular-protective role of flavonoids and especially their antioxidant properties are still under investigation. Indeed, further research is required to establish the impact of the proposed new therapeutic strategies in atherosclerosis. PMID:25410138

Tousoulis, Dimitris; Psaltopoulou, Theodora; Androulakis, Emmanuel; Papageorgiou, Nikolaos; Papaioannou, Spyridon; Oikonomou, Evangelos; Synetos, Andreas; Stefanadis, Christodoulos

2015-02-01

402

Atherosclerosis and flow in carotid arteries with authentic geometries.  

PubMed

The influence of blood flow on the depositions and development of atherosclerotic lesions have been observed and described since the 19th century. Observations have shown that depositions correlate with regions of low wall shear stress. However, the exact correlations between depositions, vessel geometry and flow parameters are not yet known. The purpose of this study was the quantification of atherosclerosis risk factors in carotid bifurcation. This artery has attracted particular interest because lesions are often found in this bifurcation. Post mortem, the arteries are excised and vessel casts are produced. Afterwards, the arteries are analyzed morphometrically. The vessel casts are used for the assessment of some geometrical parameters. 31 carotid bifurcations were analyzed in this study. Eight vessel casts were digitized and rendered three-dimensional mathematical models of the arteries. These data were imported by the computational fluid dynamics program FLUENT. Further, the blood flow was reconstructed in a computer model based on the individual vessel geometry. The flow parameters, such as velocity, pressure and wall shear stress were computed. At the same time the geometrical parameters and wall alterations are known. This permits the comparison of the anatomical shape and its flow with the distribution and level of the wall alterations. PMID:12122275

Goubergrits, L; Affeld, K; Fernandez-Britto, J; Falcon, L

2002-01-01

403

Apoptosis of endothelial cells. Contribution to the pathophysiology of atherosclerosis?  

PubMed

Endothelial cell injury is a key event in the pathogenesis of atherosclerosis. Importantly, endothelial cells in lesion-prone regions, where atherosclerotic lesions preferentially develop, are characterised by increased endothelial cell turn-over rates suggesting a mechanistic link between endothelial cell turn-over with preceding cell death and the susceptibility to atherosclerotic plaque development. The activation of the cellular suicide pathway leading to apoptosis of the endothelial cell may be an initial step in the development of atherosclerotic lesions. This hypothesis is supported by the finding that proatherosclerotic factors such as angiotensin II, oxidized low density lipoprotein, reactive oxygen species, glucose and inflammatory cytokines have all been shown to induce apoptosis of endothelial cells. In contrast, the known atheroprotective factors, such as oestrogen, nitric oxide or anti-oxidants, prevented endothelial cell apoptosis. Furthermore, laminar flow, which seems to be one of the most potent endogenous anti-atherosclerotic factor as illustrated by the focal nature of atherosclerotic lesion development in areas with turbulent or low blood flow, protects endothelial cell from apoptotic cell death. The present article summarizes the effects of pro and anti-atherosclerotic factors on endothelial cell apoptosis and provides insights into the underlying signalling events. PMID:9889419

Dimmeler, S; Hermann, C; Zeiher, A M

1998-12-01

404

The effects of endothelial progenitor cells on rat atherosclerosis.  

PubMed

Atherosclerosis (AS) is a progressive disease characterized by endothelial injury and lipid aggregation in the arterial walls. Studies have reported that endothelial progenitor cells (EPCs) derived from the bone marrow (BM) might provide an endogenous repair mechanism by differentiating into endothelial cells to replace the dysfunctional endothelium. Our study aims to investigate the effect of EPCs derived from rat BM on AS. EPCs transduced by recombinant adeno-associated virus-green fluorescent protein (GFP) were transplanted into a rat AS model. After 2 months of transplantation, the localization of GFP-labeled cells, morphology, and lipid content in the aorta were examined. GFP-labeled EPCs were found in the endothelial monolayer of the artery vessel in the GFP/EPC group. Hematoxylin and eosin staining suggested that the lipid deposits in the aortic endothelium in the EPC/GFP group were less compared with those in the untreated group. Oil Red O staining of liver slices showed that lipid droplets were obviously decreased in the GFP/EPC group. The endothelial nitric oxide synthase and apolipoprotein E mRNA levels in the GFP/EPC group were significantly higher, but the intercellular cell adhesion molecule-1 mRNA level was significantly lower compared with the control group. The results suggest that EPCs derived from the BM can repair the injured endothelium and promote an atherosclerotic lesion regression. Therefore, EPCs may provide a useful tool for the treatment of AS. PMID:24888716

Wang, Xianyou; Wang, Feng; Li, Nana; Hu, Min; Chen, Yun; Tan, Mengqun

2014-05-28

405

Nuclear microscopy investigations into the role of iron in atherosclerosis  

NASA Astrophysics Data System (ADS)

Using nuclear microscopy we have investigated elemental distributions and concentrations in aortic arch tissue sections from three groups of rabbits: (a) rabbits on normal diet (normal group), (b) rabbits on a high-cholesterol diet (control group), and (c) rabbits on a high-cholesterol diet and depleted in iron by weekly bleeding (test group). Rabbits in each group were sacrificed at 4-week time intervals, at 4, 8, 12 and 16 weeks. As early as 4 weeks, the aortic arches of control rabbits showed signs of fatty streaks and lesions, with a 2-fold average increase of iron concentration in the artery wall of cholesterol fed rabbits compared to the normal group. At 12 and 16 weeks the control group exhibited well-developed atherosclerotic lesions with an accompanying 3-fold increase in iron. The test group showed a significant reduction of lesion formation compared to the controls, and only after 12 weeks was an increase in iron concentration in the aortic arch observed. These findings show that controlled blood letting results in reduced uptake of iron by the artery wall and delayed atherosclerotic lesion formation. This correlation strongly suggests that iron has an important role in the aetiology of atherosclerosis.

Makjanic, Jagoda; Ponraj, D.; Tan, B. K. H.; Watt, F.

1999-10-01

406

Vascular expression of extracellular superoxide dismutase in atherosclerosis.  

PubMed Central

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

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

1998-01-01

407

Pentoxifylline Decreases Serum Level of Adhesion Molecules in Atherosclerosis Patients  

PubMed Central

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

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

2014-01-01

408

Systemic Delivery of MicroRNA-181b Inhibits Nuclear Factor-?B Activation, Vascular Inflammation, and Atherosclerosis in Apolipoprotein E–Deficient Mice  

PubMed Central

Rationale Activated nuclear factor (NF)-?B signaling in the vascular endothelium promotes the initiation and progression of atherosclerosis. Targeting endothelial NF-?B may provide a novel strategy to limit chronic inflammation. Objective To examine the role of microRNA-181b (miR-181b) in endothelial NF-?B signaling and effects on atherosclerosis. Methods and Results MiR-181b expression was reduced in the aortic intima and plasma in apolipoprotein E–deficient mice fed a high-fat diet. Correspondingly, circulating miR-181b in the plasma was markedly reduced in human subjects with coronary artery disease. Systemic delivery of miR-181b resulted in a 2.3-fold overexpression of miR-181b in the aortic intima of apolipoprotein E–deficient mice and suppressed NF-?B signaling revealed by bioluminescence imaging and reduced target gene expression in the aortic arch in apolipoprotein E–deficient/NF-?B-luciferase transgenic mice. MiR-181b significantly inhibited atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4+ T cells in the vessel wall. Mechanistically, miR-181b inhibited the expression of the target gene importin-?3, an effect that reduced NF-?B nuclear translocation specifically in the vascular endothelium of lesions, whereas surprisingly leukocyte NF-?B signaling was unaffected despite a 7-fold overexpression of miR-181b. Our findings uncover that NF-?B nuclear translocation in leukocytes does not involve importin-?3, but rather importin-?5, which miR-181b does not target, highlighting that inhibition of NF-?B signaling in the endothelium is sufficient to mediate miR-181b's protective effects. Conclusions Systemic delivery of miR-181b inhibits the activation of NF-?B and atherosclerosis through cell-specific mechanisms in the vascular endothelium. These findings support the rationale that delivery of miR-181b may provide a novel therapeutic approach to treat chronic inflammatory diseases such as atherosclerosis. PMID:24084690

Wara, A.K.M.; Icli, Basak; Shvartz, Eugenia; Tesmenitsky, Yevgenia; Belkin, Nathan; Li, Dazhu; Blackwell, Timothy S.; Sukhova, Galina K.; Croce, Kevin; Feinberg, Mark W.

2014-01-01

409

Dietary coenzyme Q10 does not protect against cigarette smoke-augmented atherosclerosis in apoE-deficient mice  

Microsoft Academic Search

Dietary coenzyme Q10 reduces spontaneous atherosclerosis in the apoE-deficient mouse model of experimental atherosclerosis. We have shown previously that exposure to sidestream cigarette smoke (SSCS) enhances atherosclerotic lesion formation in apoE-deficient mice. The aim of the present study was to determine if CoQ10 protected against SSCS-mediated atherosclerosis. Female apoE-deficient mice were fed a saturated fat-enriched diet (SFD) alone, or supplemented

C. Gary Gairola; Deborah A. Howatt; Alan Daugherty

2010-01-01

410

Genomic analyses of induced hypercholesterolemia and atherosclerosis in a mixed breed colony of dogs and developmental abnormalities in the Havanese  

E-print Network

of the animal models of atherosclerosis to the natural atherosclerosis in humans. Model Phylogenetically close to human Metabolism Diet Atherosclerosis development Primate +++ Similar Omnivore Natural and Induced Pig ++ Similar Omnivore Induced... Dog ++ Dissimilar Carnivore Induced Rabbit + Dissimilar Herbivore Induced Rat + Similar Omnivore Induced Mouse + Similar Herbivore Induced The dog has been used as a model for many human hereditary diseases, both with single gene and complex...

Starr, Alison Nicole

2009-05-15

411

Regression of atherosclerosis by the intravenous infusion of specific biochemical nutrient substrates in animals and humans.  

PubMed Central

Preliminary studies in 400 New Zealand albino rabbits produced a reliable animal model of nutrient-induced atherosclerosis that simulated that observed in humans. Atherosclerosis was then induced in an additional 1600 rabbits in sets of 40 animals each, maintaining plasma cholesterol concentrations between 1000 and 2000 mg/dL for 6-20 weeks. In each set, 10 control rabbits were killed to document baseline atherosclerosis, and the other 30 rabbits were assigned randomly to one of three groups of 10 rabbits. Groups of 10 rabbits were either continued on the atherogenic diet (group I), given standard laboratory rabbit pellets (group II), or infused continuously with specially formulated anticholesterol solutions via central venous catheters (group III) for 6 weeks. At autopsy, atherosclerotic lesions consistently involved 85-95% of the aorta in group I. In group II, atherosclerosis was comparable with the baseline control group with no regression. In group III, regression of atherosclerosis by 90-95% was consistently documented. Correlations between plasma amino acids and plasma cholesterol concentrations were established in four humans with severe atherosclerosis to maximize the cholesterol reduction capacity of the amino acid formulation. Infusion of the modified total parenteral nutrition solution induced prompt reduction in plasma cholesterol levels by 40-60% regardless of the initial level and was accompanied by evidence of regression of atherosclerosis after a 90-day infusion therapy period. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 13. Fig. 14. Fig. 15. Fig. 16. Fig. 18. Fig. 19. Fig. 20. PMID:3115205

Dudrick, S J

1987-01-01

412

T?Helper Type 1 Bias in Healthy People Is Associated With Cytomegalovirus Serology and Atherosclerosis: The Multi?Ethnic Study of Atherosclerosis  

PubMed Central

Background Although T?helper type 1 (Th1) cells are considered important in atherosclerosis, the relationships between Th1 and Th2 cells and atherosclerosis have not been examined in population?based studies. Methods and Results We measured Th cells as a percentage of lymphocytes by flow cytometry using CD4 staining (%CD4) in 917 participants of the Multi?Ethnic Study of Atherosclerosis. We also measured interferon gamma–positive and interleukin?4?positive CD4+ cells, representing Th1 and Th2 subpopulations (%Th1 and %Th2), respectively. We found that %CD4 was 1.5% lower per 10 years of age (P<0