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1

Irbesartan  

MedlinePLUS

... Your blood pressure should be checked regularly to determine your response to irbesartan.Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.It is important for you to keep a ...

2

Renin inhibition by aliskiren prevents atherosclerosis progression: comparison with irbesartan, atenolol, and amlodipine.  

PubMed

Hypertension is associated with increased risk of cardiovascular diseases. Antihypertensive treatment, particularly blockade of the renin-angiotensin system, contributes to prevent atherosclerosis-mediated cardiovascular events. Direct comparison of different antihypertensive treatments on atherosclerosis and particularly plaque stabilization is sparse. ApoE(-/-) mice with vulnerable (2-kidney, 1-clip renovascular hypertension model) or stable (1-kidney, 1-clip renovascular hypertension model) atherosclerotic plaques were used. Mice were treated with aliskiren (renin inhibitor), irbesartan (angiotensin-receptor blocker), atenolol (beta-blocker), or amlodipine (calcium channel blocker). Atherosclerosis characteristics were assessed. Hemodynamic and hormonal parameters were measured. Aliskiren and irbesartan significantly prevented atherosclerosis progression in 2-kidney, 1-clip mice. Indeed, compared with untreated animals, plaques showed thinner fibrous cap (P<0.05); smaller lipid core (P<0.05); decreased media degeneration, layering, and macrophage content (P<0.05); and increased smooth muscle cell content (P<0.05). Interestingly, aliskiren significantly increased the smooth muscle cell compared with irbesartan. Despite similar blood pressure lowering, only partial plaque stabilization was attained by atenolol and amlodipine. Amlodipine increased plaque smooth muscle cell content (P<0.05), whereas atenolol decreased plaque inflammation (P<0.05). This divergent effect was also observed in 1-kidney, 1-clip mice. Normalizing blood pressure by irbesartan increased the plasma renin concentration (5932+/-1512 ng/mL per hour) more than normalizing it by aliskiren (16085+/-5628 ng/mL per hour). Specific renin-angiotensin system blockade prevents atherosclerosis progression. First, evidence is provided that direct renin inhibition mediates atherosclerotic plaque stabilization. In contrast, beta-blocker and calcium channel blocker treatment only partially stabilize plaques differently influencing atherogenesis. Angiotensin II decisively mediates plaque vulnerability. The plasma renin concentration measurement by an indirect method did not confirm the excessive increase of plasma renin concentration reported in the literature during aliskiren compared with irbesartan or amlodipine treatment. PMID:18391092

Nussberger, Jürg; Aubert, Jean-François; Bouzourene, Karima; Pellegrin, Maxime; Hayoz, Daniel; Mazzolai, Lucia

2008-04-07

3

Suppression of Atherosclerosis in Cholesterolemic Rabbits by Dimethyl Sulfoxide.  

National Technical Information Service (NTIS)

The results of this study indicate that DMSO retards the development of dietary cholesterol-induced atherosclerosis in rabbits and suppresses the accumulation of cholesterol in tissues despite severe hypercholesterolemia. While the mechanism of action of ...

D. L. Layman S. S. Alam K. C. Newcomb

1983-01-01

4

Irbesartan and Hydrochlorothiazide  

MedlinePLUS

Combination productThis product contains two medications, irbesartan and hydrochlorothiazide. Please see the individual monographs for information about each of the medications contained in this product.

5

Interleukin-10 overexpression in macrophages suppresses atherosclerosis in hyperlipidemic mice  

PubMed Central

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

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

2010-01-01

6

Atherosclerosis  

MedlinePLUS

... Cholesterol • Home • About Cholesterol • Why Cholesterol Matters Introduction Atherosclerosis • Understand Your Risk for High Cholesterol • Symptoms, Diagnosis & Monitoring • Prevention & Treatment • Tools & Resources Sign up for our Heart-Health ...

7

Long-term treatment with propagermanium suppresses atherosclerosis in WHHL rabbits.  

PubMed

Macrophages play an important role in the pathogenesis of atherosclerosis, for which monocyte chemoattractant protein (MCP)-1 and CCR2 chemokine receptors may be involved. The authors have recently demonstrated that propagermanium exerts inhibitory effect on the CCR2 receptors. In the current study, the authors examined whether the organic germanium suppresses the MCP-1-induced monocyte migration in vitro and the development of atherosclerosis in WHHL rabbits in vivo. In the in vitro experiment, propagermanium concentration-dependently suppressed the MCP-1-induced migration of THP-1 cells. In the in vivo experiment, 20 WHHL rabbits were randomly divided into two groups; one group was treated with oral administration with propagermanium (9 mg/kg/day) for 3 months, and another group served as a control (n = 10 each). After 3 months, the aorta was isolated and stained with oil red O staining, and neointimal formation was quantified. Macrophage accumulation in the aorta was also evaluated by immunostaining. Long-term treatment with propagermanium did not affect the serum lipid profiles. However, the treatment significantly suppressed the oil red O-positive area of the total aorta (p < 0.05). Similarly, propagermanium significantly suppressed the intimal lesions (maximal intimal thickness and intimal area) and macrophage staining-positive area (all p < 0.05). A significant positive correlation was noted between macrophage staining-positive area and intimal lesions (p < 0.0001). These results indicate that long-term treatment with propagermanium suppresses the development of atherosclerosis in WHHL rabbits, suggesting its usefulness for the treatment of atherosclerotic vascular disease in humans. PMID:12548076

Eto, Yasuhiro; Shimokawa, Hiroaki; Tanaka, Eriko; Morishige, Kunio; Fuchigami, Masahiro; Ishiwata, Yoshiro; Matsushima, Kouji; Takeshita, Akira

2003-02-01

8

Treg-mediated suppression of atherosclerosis requires MYD88 signaling in DCs  

PubMed Central

TLR activation on CD11c+ DCs triggers DC maturation, which is critical for T cell activation. Given the expansion of CD11c+ DCs during the progression of atherosclerosis and the key role of T cell activation in atherogenesis, we sought to understand the role of TLR signaling in CD11c+ DCs in atherosclerosis. To this end, we used a mouse model in which a key TLR adaptor involved in DC maturation, MYD88, is deleted in CD11c+ DCs. We transplanted bone marrow containing Myd88-deficient CD11c+ DCs into Western diet–fed LDL receptor knockout mice and found that the transplanted mice had decreased activation of effector T cells in the periphery as well as decreased infiltration of both effector T cells and Tregs in atherosclerotic lesions. Surprisingly, the net effect was an increase in atherosclerotic lesion size due to an increase in the content of myeloid-derived inflammatory cells. The mechanism involves increased lesional monocyte recruitment associated with loss of Treg-mediated suppression of MCP-1. Thus, the dominant effect of MYD88 signaling in CD11c+ DCs in the setting of atherosclerosis is to promote the development of atheroprotective Tregs. In the absence of MYD88 signaling in CD11c+ DCs, the loss of this protective Treg response trumps the loss of proatherogenic T effector cell activation.

Subramanian, Manikandan; Thorp, Edward; Hansson, Goran K.; Tabas, Ira

2012-01-01

9

Suppression of coronary atherosclerosis by helix B surface Peptide, a nonerythropoietic, tissue-protective compound derived from erythropoietin.  

PubMed

Erythropoietin (EPO), a type I cytokine originally identified for its critical role in hematopoiesis, has been shown to have nonhematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its potential clinical use in nonanemic patients. In the present study, we investigated the antiatherosclerotic effects of helix B surface peptide (HBSP), a nonerythropoietic, tissue-protective compound derived from EPO, by using human umbilical vein endothelial cells (HUVECs) and human monocytic THP-1 cells in vitro and Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits in vivo. In HUVECs, HBSP inhibited apoptosis (?70%) induced by C-reactive protein (CRP), a direct mediator of atherosclerosis. By using a small interfering RNA approach, Akt was shown to be a key molecule in HBSP-mediated prevention of apoptosis. HBSP also attenuated CRP-induced production of tumor necrosis factor (TNF)-? and matrix metalloproteinase-9 in THP-1 cells. In the WHHLMI rabbit, HBSP significantly suppressed progression of coronary atherosclerotic lesions as assessed by mean cross-sectional stenosis (HBSP 21.3 ± 2.2% versus control peptide 38.0 ± 2.7%) and inhibited coronary artery endothelial cell apoptosis with increased activation of Akt. Furthermore, TNF-? expression and the number of M1 macrophages and M1/M2 macrophage ratio in coronary atherosclerotic lesions were markedly reduced in HBSP-treated animals. In conclusion, these data demonstrate that HBSP suppresses coronary atherosclerosis, in part by inhibiting endothelial cell apoptosis through activation of Akt and in association with decreased TNF-? production and modified macrophage polarization in coronary atherosclerotic lesions. Because HBSP does not have the prothrombotic effects of EPO, our study may provide a novel therapeutic strategy that prevents progression of coronary artery disease. PMID:23648638

Ueba, Hiroto; Shiomi, Masashi; Brines, Michael; Yamin, Michael; Kobayashi, Tsutomu; Ako, Junya; Momomura, Shin-Ichi; Cerami, Anthony; Kawakami, Masanobu

2013-07-24

10

Suppression of Coronary Atherosclerosis by Helix B Surface Peptide, a Nonerythropoietic, Tissue-Protective Compound Derived from Erythropoietin  

PubMed Central

Erythropoietin (EPO), a type I cytokine originally identified for its critical role in hematopoiesis, has been shown to have nonhematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its potential clinical use in nonanemic patients. In the present study, we investigated the antiatherosclerotic effects of helix B surface peptide (HBSP), a nonerythropoietic, tissue-protective compound derived from EPO, by using human umbilical vein endothelial cells (HUVECs) and human monocytic THP-1 cells in vitro and Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits in vivo. In HUVECs, HBSP inhibited apoptosis (?70%) induced by C-reactive protein (CRP), a direct mediator of atherosclerosis. By using a small interfering RNA approach, Akt was shown to be a key molecule in HBSP-mediated prevention of apoptosis. HBSP also attenuated CRP-induced production of tumor necrosis factor (TNF)-? and matrix metalloproteinase-9 in THP-1 cells. In the WHHLMI rabbit, HBSP significantly suppressed progression of coronary atherosclerotic lesions as assessed by mean cross-sectional stenosis (HBSP 21.3 ± 2.2% versus control peptide 38.0 ± 2.7%) and inhibited coronary artery endothelial cell apoptosis with increased activation of Akt. Furthermore, TNF-? expression and the number of M1 macrophages and M1/M2 macrophage ratio in coronary atherosclerotic lesions were markedly reduced in HBSP-treated animals. In conclusion, these data demonstrate that HBSP suppresses coronary atherosclerosis, in part by inhibiting endothelial cell apoptosis through activation of Akt and in association with decreased TNF-? production and modified macrophage polarization in coronary atherosclerotic lesions. Because HBSP does not have the prothrombotic effects of EPO, our study may provide a novel therapeutic strategy that prevents progression of coronary artery disease.

Ueba, Hiroto; Shiomi, Masashi; Brines, Michael; Yamin, Michael; Kobayashi, Tsutomu; Ako, Junya; Momomura, Shin-ichi; Cerami, Anthony; Kawakami, Masanobu

2013-01-01

11

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

Microsoft Academic Search

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

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

1998-01-01

12

ApoE derived from adipose tissue does not suppress atherosclerosis or correct hyperlipidemia in apoE knockout mice.  

PubMed

The synthesis of apoE by adipocytes has profound effects on adipose tissue lipid flux and gene expression. Using adipose tissue transplantation from wild-type (WT) to apoE knockout (EKO) mice, we show that adipose tissue also contributes to circulating apoE. Different from circulating apoE produced by bone marrow transplantation (BMT), however, adipose tissue-derived apoE does not correct hyperlipidemia or suppress atherosclerosis. ApoE secreted by macrophages has a more acidic isoform distribution, and it increases binding of reconstituted VLDL particles to hepatocytes and fibroblasts more effectively than apoE secreted by adipocytes. The incremental binding can be entirely accounted for by binding to the LDL receptor. After BMT into EKO hosts, plasma cholesterol and macrophage-derived apoE are largely within IDL/LDL- and HDL-sized particles. After adipose tissue transplantation, most cholesterol and adipocyte apoE remain in VLDL. After BMT, circulating apoE no longer demonstrates predominance of acidic isoforms compared with that circulating after fat transplantation. In conclusion, fat transplantation provides circulating apoE levels similar to those provided by bone marrow transplantation, but it does not suppress hyperlipidemia or atherosclerosis. A potential mechanism contributing to this difference is differential binding to cell surface lipoprotein receptors. PMID:23071294

Huang, Zhi H; Reardon, Catherine A; Subbaiah, Papasani V; Getz, Godfrey S; Mazzone, Theodore

2012-10-15

13

Irbesartan administration therapeutically influences circulating endothelial progenitor cell and microparticle mobilization by involvement of pro-inflammatory cytokines.  

PubMed

Circulating microparticles (MPs) and endothelial progenitor cells (EPCs) correlate with endothelial dysfunction and contribute to the pathogenesis of atherosclerosis. In this context, we explored whether the angiotensin II type I receptor antagonist, irbesartan, exerts a pharmacological control in the atherosclerotic process by the improvement of EPC mobilization and inhibitory effects on MP release and VEGF and SDF-1? levels in the hypertensive-hypercholesterolemic (HH) hamster model. The HH hamsters were treated with irbesartan (50mg/kg b.w/day administered by gavage) for 4 month (HHI). We analyzed MP/EPC infiltration in vascular wall before and after irbesartan administration as well as the endothelial function and expression of VEGF/SDF-1? in plasma and tissue and of molecular pathways activated by them. The results showed that treatment with irbesartan significantly increased EPC infiltration and decreased MP infiltration. The mechanisms underlying this response include the reduction/increase of a number of specific membrane receptors exposed by MPs (TF, P-Selectin, E-Selectin, PSGL-1, Rantes), respectively, by EPCs (?2-Integrins, ?4?1-integrin), the augmentation of endothelium-mediated vasodilation and the reduction of protein expression of VEGF/SDF-1? followed by: (1) the diminishment of pro-inflammatory endothelial cytokines: VEGFR1, VEGFR2, CXCR4, Tie2, PIGF with role in EPC homing to sites of damaged endothelium; and (2) the increase of protein expression of COX-2, PGI2 synthase molecules with role in the improvement of arterial wall vasodilatation. In conclusion, the study underlines that irbesartan administration therapeutically improves/reduces EPC, respectively, MP mobilization and this action may be of salutary relevance contributing to its beneficial cardiovascular effects. PMID:23639758

Georgescu, Adriana; Alexandru, Nicoleta; Nemecz, Miruna; Titorencu, Irina; Popov, Doina

2013-04-29

14

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

PubMed Central

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

Gialama, Fotini; Maniadakis, Nikos

2013-01-01

15

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

PubMed Central

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

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

2012-01-01

16

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

PubMed Central

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

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

2009-01-01

17

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.

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

2012-01-01

18

Suppressive Impact of Anethum Graveolens Consumption on Biochemical Risk Factors of Atherosclerosis in Hypercholesterolemic Rabbits  

PubMed Central

Background: We aimed to determine the effects of Anethum graveolens (Dill) powder on postprandial lipid profile, markers of oxidation and endothelial activation when added to a fatty meal. Methods: In an experimental study, 32 rabbits were randomly designated into four diet groups: normal diet, high cholesterol diet (1%), high cholesterol diet plus 5% (w/w) dill powder and high cholesterol diet plus lovastatin (10 mg/kg, bw). The concentrations of glucose, total cholesterol (TC), low-density lipoproteins-cholesterol (LDL-C), alanine aminotransferase (alt), aspartate aminotransferase (ast), fibrinogen, factor VII, apolipoprotein B (ApoB), nitrite and nitrate were measured in blood samples following 15 h of fasting and 3 h after feeding. Results: Concurrent use of A. graveolens powder or lovastatin significantly decreased ALT, TC, glucose, fibrinogen and LDL-C values in comparison with hypercholesterolemic diet group (P < 0.05). Consumption of A. graveolens or lovastatin did not change factor VII, ApoB, nitrite and nitrate levels significantly in comparison with hypercholesterolemic diet group. Intake of A. graveolens significantly decreased serum AST compared to hypercholesterolemic diet. Conclusions: A. graveolens might have some protective values against atherosclerosis and that it significantly affects some biochemical risk factors of this disease. Our findings also confirm the potential harmful effects of oxidized fats and the importance of dietary polyphenols in the meal.

Setorki, Mahbubeh; Rafieian-Kopaei, Mahmoud; Merikhi, Alireza; Heidarian, Esfandiar; Shahinfard, Najmeh; Ansari, Roya; Nasri, Hamid; Esmael, Nafiseh; Baradaran, Azar

2013-01-01

19

Melatonin ameliorates vascular endothelial dysfunction, inflammation, and atherosclerosis by suppressing the TLR4/NF-?B system in high-fat-fed rabbits.  

PubMed

Vascular endothelial dysfunction (VED) and inflammation contribute to the initiation and progression of atherosclerosis. Melatonin (MLT) normalizes lipid profile, improves endothelial function, and possesses anti-inflammatory properties. However, the precise mechanisms are still unclear. This study investigated whether MLT could ameliorate VED, inflammation, and atherosclerosis by suppressing the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-?B) system in high-fat-fed rabbits. Rabbits were randomly divided into three groups that received a standard diet (control group), high-cholesterol diet (atherosclerosis group), or high-cholesterol diet plus 10 mg/kg/day MLT (MLT group) for 12 wk. After treatment, high-fat diet significantly increased serum lipid and inflammatory markers in rabbits in atherosclerosis group compared with that in control group. In addition, high-fat diet also induced VED and typical atherosclerotic plaque formation and increased intima/media thickness ratio, which were significantly improved by MLT therapy as demonstrated in MLT group. Histological and immunoblot analysis further showed that high-fat diet enhanced the expressions of TLR4, myeloid differentiation primary response protein (MyD88), and NF-?B p65, but decreased inhibitor of NF-?B (I?B) expression. By contrast, MLT therapy decreased the expressions of TLR4, MyD88, and NF-?B p65 and increased I?B expression. This study has demonstrated that MLT ameliorates lipid metabolism, VED, and inflammation and inhibits the progression of atherosclerosis in high-fat-fed rabbits. Moreover, our study indicates for the first time that suppression of the TLR4/NF-?B system in local vasculature with atherosclerotic damage is important for the protective effects of MLT. PMID:24006943

Hu, Ze-Ping; Fang, Xiao-Ling; Fang, Nan; Wang, Xiao-Bian; Qian, Hai-Yan; Cao, Zhong; Cheng, Yuan; Wang, Bang-Ning; Wang, Yuan

2013-09-06

20

Resveratrol, Wine, and Atherosclerosis  

PubMed Central

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

Prasad, Kailash

2012-01-01

21

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.

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

2013-01-01

22

Targeting annexin A7 by a small molecule suppressed the activity of phosphatidylcholine-specific phospholipase C in vascular endothelial cells and inhibited atherosclerosis in apolipoprotein E?/? mice  

PubMed Central

Phosphatidylcholine-specific phospholipase C (PC-PLC) is a key factor in apoptosis and autophagy of vascular endothelial cells (VECs), and involved in atherosclerosis in apolipoprotein E?/? (apoE?/?) mice. But the endogenous regulators of PC-PLC are not known. We recently found a small chemical molecule (6-amino-2, 3-dihydro-3-hydroxymethyl-1, 4-benzoxazine, ABO) that could inhibit oxidized low-density lipoprotein (oxLDL)-induced apoptosis and promote autophagy in VECs, and further identified ABO as an inhibitor of annexin A7 (ANXA7) GTPase. Based on these findings, we hypothesize that ANXA7 is an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO may inhibit atherosclerosis in apoE?/? mice. In this study, we tested our hypothesis. The results showed that ABO suppressed oxLDL-induced increase of PC-PLC level and activity and promoted the co-localization of ANXA7 and PC-PLC in VECs. The experiments of ANXA7 knockdown and overexpression demonstrated that the action of ABO was ANXA7-dependent in cultured VECs. To investigate the relation of ANXA7 with PC-PLC in atherosclerosis, apoE?/? mice fed with a western diet were treated with 50 or 100?mg/kg/day ABO. The results showed that ABO decreased PC-PLC levels in the mouse aortic endothelium and PC-PLC activity in serum, and enhanced the protein levels of ANXA7 in the mouse aortic endothelium. Furthermore, both dosages of ABO significantly enhanced autophagy and reduced apoptosis in the mouse aortic endothelium. As a result, ABO significantly reduced atherosclerotic plaque area and effectively preserved a stable plaques phenotype, including reduced lipid deposition and pro-inflammatory macrophages, increased anti-inflammatory macrophages, collagen content and smooth muscle cells, and less cell death in the plaques. In conclusion, ANXA7 was an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO inhibited atherosclerosis in apoE?/? mice.

Li, H; Huang, S; Wang, S; Zhao, J; Su, L; Zhao, B; Zhang, Y; Zhang, S; Miao, J

2013-01-01

23

Targeting annexin A7 by a small molecule suppressed the activity of phosphatidylcholine-specific phospholipase C in vascular endothelial cells and inhibited atherosclerosis in apolipoprotein E(-/-) mice.  

PubMed

Phosphatidylcholine-specific phospholipase C (PC-PLC) is a key factor in apoptosis and autophagy of vascular endothelial cells (VECs), and involved in atherosclerosis in apolipoprotein E(-/-) (apoE(-/-)) mice. But the endogenous regulators of PC-PLC are not known. We recently found a small chemical molecule (6-amino-2, 3-dihydro-3-hydroxymethyl-1, 4-benzoxazine, ABO) that could inhibit oxidized low-density lipoprotein (oxLDL)-induced apoptosis and promote autophagy in VECs, and further identified ABO as an inhibitor of annexin A7 (ANXA7) GTPase. Based on these findings, we hypothesize that ANXA7 is an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO may inhibit atherosclerosis in apoE(-/-) mice. In this study, we tested our hypothesis. The results showed that ABO suppressed oxLDL-induced increase of PC-PLC level and activity and promoted the co-localization of ANXA7 and PC-PLC in VECs. The experiments of ANXA7 knockdown and overexpression demonstrated that the action of ABO was ANXA7-dependent in cultured VECs. To investigate the relation of ANXA7 with PC-PLC in atherosclerosis, apoE(-/-) mice fed with a western diet were treated with 50 or 100?mg/kg/day ABO. The results showed that ABO decreased PC-PLC levels in the mouse aortic endothelium and PC-PLC activity in serum, and enhanced the protein levels of ANXA7 in the mouse aortic endothelium. Furthermore, both dosages of ABO significantly enhanced autophagy and reduced apoptosis in the mouse aortic endothelium. As a result, ABO significantly reduced atherosclerotic plaque area and effectively preserved a stable plaques phenotype, including reduced lipid deposition and pro-inflammatory macrophages, increased anti-inflammatory macrophages, collagen content and smooth muscle cells, and less cell death in the plaques. In conclusion, ANXA7 was an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO inhibited atherosclerosis in apoE(-/-) mice. PMID:24052074

Li, H; Huang, S; Wang, S; Zhao, J; Su, L; Zhao, B; Zhang, Y; Zhang, S; Miao, J

2013-09-19

24

The Efficacy and Safety of Irbesartan in Treating Essential Hypertension  

Microsoft Academic Search

Background:Irbersatan, an orally active antihypertensive agent, effectively reduce blood pressure by di- rectly blocking angiotensin ? receptors without any significant adverse effects. The purpose of this study is to evaluate the efficacy and safety of irbesartan in patients with mild to moderate hypertension. Methods: This study enrolled 83 patients who had diastolic pressure above 95 mmHg and below 110 mmHg

Cheol Eom; Joon-Han Shin; Han-Soo Kim; Seung-Jae Tahk; Jong-Hoon Koh; Byung-il William Choi; Eui-Soo Hong; Jeong-Kee Seo; Jun Kwan; Keum-Soo Park; Woo-Hyung Lee

25

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.

26

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

PubMed Central

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

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

2011-01-01

27

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

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

2013-09-13

28

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.

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

2013-01-01

29

Extracoronary atherosclerosis  

SciTech Connect

This book contains 43 selections. Some of the titles are: Cerebral Blood Flow Tomography by Single Photon Emission Computerized Tomography Using /sup 133/Xe in Cerebrovascular Disease; Lipoproteins, Cholesterol Ester Transport and Atherogenesis; Genetic Polymorphisms and Atherosclerosis; and Studies on Lipolytic Enzymes in Cell Culture.

Ventura, A.; Crepaldi, G.; Senin, U.

1986-01-01

30

Extractive-spectrophotometric determination of disopyramide and irbesartan in their pharmaceutical formulation  

NASA Astrophysics Data System (ADS)

Picric acid, bromocresol green, bromothymol blue, cobalt thiocyanate and molybdenum(V) thiocyanate have been tested as spectrophotometric reagents for the determination of disopyramide and irbesartan. Reaction conditions have been optimized to obtain coloured comoplexes of higher sensitivity and longer stability. The absorbance of ion-pair complexes formed were found to increases linearity with increases in concentrations of disopyramide and irbesartan which were corroborated by correction coefficient values. The developed methods have been successfully applied for the determination of disopyramide and irbesartan in bulk drugs and pharmaceutical formulations. The common excipients and additives did not interfere in their determination. The results obtained by the proposed methods have been statistically compared by means of student t-test and by the variance ratio F-test. The validity was assessed by applying the standard addition technique. The results were compared statistically with the official or reference methods showing a good agreement with high precision and accuracy.

Abdellatef, Hisham E.

2007-04-01

31

Extractive-spectrophotometric determination of disopyramide and irbesartan in their pharmaceutical formulation.  

PubMed

Picric acid, bromocresol green, bromothymol blue, cobalt thiocyanate and molybdenum(V) thiocyanate have been tested as spectrophotometric reagents for the determination of disopyramide and irbesartan. Reaction conditions have been optimized to obtain coloured comoplexes of higher sensitivity and longer stability. The absorbance of ion-pair complexes formed were found to increases linearity with increases in concentrations of disopyramide and irbesartan which were corroborated by correction coefficient values. The developed methods have been successfully applied for the determination of disopyramide and irbesartan in bulk drugs and pharmaceutical formulations. The common excipients and additives did not interfere in their determination. The results obtained by the proposed methods have been statistically compared by means of student t-test and by the variance ratio F-test. The validity was assessed by applying the standard addition technique. The results were compared statistically with the official or reference methods showing a good agreement with high precision and accuracy. PMID:16920393

Abdellatef, Hisham E

2006-06-27

32

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

Microsoft Academic Search

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

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

33

The KARTAN study: A postmarketing assessment of Irbesartan in patients with hypertension  

Microsoft Academic Search

Background: An important purpose of postmarketing surveillance of drugs is to better characterize the safety profile of drug therapy in the clinical setting. Another goal is to confirm the effectiveness of these drugs in patients who are candidates for antihypertensive therapy and who may have been excluded from Phase III studies. Irbesartan is a long-acting angiotensin II-receptor blocker specific for

Francisco J. Morales-Olivas; Ignacio Arístegui; Luis Estañ; José L. Rodicio; Alfonso Moreno; Vicente Gil; Gloria Ferrón; Olga Velasco

2004-01-01

34

Effect of irbesartan on erectile function in patients with hypertension and metabolic syndrome  

Microsoft Academic Search

Pathogenesis of erectile dysfunction (ED) is related to endothelial dysfunction and therefore associated with cardiovascular risk factors. Patients with a combination of risk factors, as in metabolic syndrome, are thus likely to have an increased risk of developing endothelial and ED. The angiotensin receptor antagonist irbesartan has been shown to improve endothelial function in cardiovascular high-risk patients, which suggests a

M Baumhäkel; N Schlimmer; M Böhm

2008-01-01

35

Determinants of persistence in hypertensive patients treated with irbesartan: results of a postmarketing survey  

PubMed Central

Background Persistence is a key factor for long-term blood pressure control, which is of high prognostic importance for patients at increased cardiovascular risk. Here we present the results of a post-marketing survey including 4769 hypertensive patients treated with irbesartan in 886 general practices in Switzerland. The goal of this survey was to evaluate the tolerance and the blood pressure lowering effect of irbesartan as well as the factors affecting persistence in a large unselected population. Methods Prospective observational survey conducted in general practices in all regions of Switzerland. Previously untreated and uncontrolled pre-treated patients were started with a daily dose of 150 mg irbesartan and followed up to 6 months. Results After an observation time slightly exceeding 4 months, the average reduction in systolic and diastolic blood pressure was 20 (95% confidence interval (CI) -19.6 to -20.7 mmHg) and 12 mmHg (95% CI -11.4 to -12.1 mmHg), respectively. At this time, 26% of patients had a blood pressure < 140/90 mmHg and 60% had a diastolic blood pressure < 90 mmHg. The drug was well tolerated with an incidence of adverse events (dizziness, headaches,...) of 8.0%. In this survey more than 80% of patients were still on irbesartan at 4 month. The most important factors predictive of persistence were the tolerability profile and the ability to achieve a blood pressure target ? 140/90 mmHg before visit 2. Patients who switched from a fixed combination treatment tended to discontinue irbesartan more often whereas those who abandoned the previous treatment because of cough (a class side effect of ACE-Inhibitors) were more persistent with irbesartan. Conclusion The results of this survey confirm that irbesartan is effective, well tolerated and well accepted by patients, as indicated by the good persistence. This post-marketing survey also emphasizes the importance of the tolerability profile and of achieving an early control of blood pressure as positive predictors of persistence.

Burnier, Michel; Hess, Bernhard; Greminger, Peter; Waeber, Bernard

2005-01-01

36

ApoE suppresses atherosclerosis by reducing lipid accumulation in circulating monocytes and the expression of inflammatory molecules on monocytes and vascular endothelium  

PubMed Central

Objective We investigated atheroprotective properties of apoE beyond its ability to lower plasma cholesterol. We hypothesized that apoE reduces atherosclerosis by decreasing lipid accumulation in circulating monocytes and the inflammatory state of monocytes and the vascular endothelium. Methods and Results We developed mice with spontaneous hyperlipidemia with and without plasma apoE: Hypomorphic apoE mice deficient in low-density lipoprotein receptor (Apoeh/hLdlr–/–) were compared to Apoe–/–Ldlr–/– mice. Despite 4-fold more plasma apoE than WT mice, Apoeh/hLdlr–/– mice displayed similar plasma cholesterol as Apoe–/–Ldlr–/– mice but developed 4-fold less atherosclerotic lesions by 5 months of age. The aortic arch of Apoeh/hLdlr–/– mice showed decreased endothelial expression of ICAM-1, PECAM-1, and JAM-A. In addition, Apoeh/hLdlr–/– mice had less circulating leukocytes and pro-inflammatory Ly6Chigh monocytes. These monocytes had decreased neutral lipid content and reduced surface expression of ICAM-1, VLA-4, and L-Selectin. Apoeh/hLdlr–/– mice displayed increased levels of apoA1-rich HDL that were potent in promoting cellular cholesterol efflux. Conclusions Our findings suggest that apoE reduces atherosclerosis in the setting of hyperlipidemia by increasing plasma apoA1-HDL that likely contribute to reduce intracellular lipid accumulation and thereby the activation of circulating leukocytes and the vascular endothelium.

Gaudreault, Nathalie; Kumar, Nikit; Posada, Jessica M.; Stephens, Kyle B.; de Mochel, Nabora Soledad Reyes; Eberle, Delphine; Olivas, Victor R.; Kim, Roy Y.; Harms, Matthew J.; Johnson, Amy; Messina, Louis M.; Rapp, Joseph H.; Raffai, Robert L.

2012-01-01

37

Regulatory T cells and Atherosclerosis  

PubMed Central

Atherosclerosis is a chronic autoimmune inflammatory disease. The involvement of both innate and adaptive immune responses in the pathogenesis of the disease has been well recognized. Tregs are an essential part of the immune system and have indispensable functions in maintaining immune system homeostasis, mediating peripheral tolerance, preventing autoimmune diseases, and suppressing inflammatory and proatherogenic immune response. Tregs carry out their immunosuppressive functions via several mechansims. One of the well-documented suppressive mechanisms of Tregs is the secretion of anti-inflammatory cytokines including IL-10, TGF-?, and IL-35. Studies have found that IL-10 and TGF-? have atheroprotective properties. In addition, Tregs can suppress the activity of proatherogenic effector T cells, suggesting an atheroprotective role. In fact, fewer Tregs are found in atherogenic ApoE?/? mice comparing to wild-type mice, suggesting an uncontrolled balance between weakened Tregs and effector T cells in atherogenesis. Some clinical studies of autoimmune diseases also suggest that decreased Tregs numbers are associated with increased disease activity. The importance of Tregs in many autoimmune diseases and experimental atherosclerosis has been established in in vivo and in vitro studies. However, the roles of Tregs in atherosclerosis in the clinical setting remains to be further characterized.

Pastrana, Jahaira Lopez; Sha, Xiaojin; Virtue, Anthony; Mai, Jietang; Cueto, Ramon; Lee, In Ae; Wang, Hong; Yang, Xiao-feng

2013-01-01

38

Antihypertensive efficacy of irbesartan 300 mg alone or in combination with hydrochlorothiazide in essential hypertensives  

Microsoft Academic Search

The aim of this study was to assess the BP control achieved in essential hypertensives (EH) treated with 300 mg irbesartan (I 300) od combined with 12.5 hydrochlorothiazide (I+HCTZ) when necessary.3.313 EH, mean age 59 y, 52.1% female, were enrolled in the study. BP was measured twice in the seated position. I 300 od was administered and 6 weeks later

Manuel O. Luque; Jacinto L. Ortiz; Francisco J. Morales; Gloria H. Ferron; Olga L. Velasco

2002-01-01

39

Short and long term effects of irbesartan in normotensives with exaggerated blood pressure response during exercise  

Microsoft Academic Search

Normotensives with exaggerated blood pressure response during exercise have impaired test parameters associated with autonomic nervous activity. We studied the short and long term effects of the angiotensin receptor blocker irbesartan on these parameters.48 subjects(36 male,12 female, mean age 58,42 ± 11,29yrs)-group A- free from known cardiovascular diseases and negative for myocardial ischemia, undergoing exercise testing for various reasons, with

Ilias Zarkos; Irini Vrana; Eleftherios Thireos; Nearchos Nearchou; Gerasimos Livieratos; Aikaterini Mitropoulou; Christos Tolis; Vasilis Tolis

2005-01-01

40

Irbesartan effects on renal function in patients with renal impairment and hypertension: a drug-withdrawal study.  

PubMed

The blood-pressure lowering activity, tolerability, and safety of irbesartan was evaluated in 52 hypertensive patients with chronic renal insufficiency. After a 3-week placebo period, once-daily irbesartan was administered for 12 weeks at a daily dose of 150 mg titrated to 300 mg. A second, non-angiotensin-converting enzyme inhibitor, antihypertensive drug was added after 8 weeks as needed. Twenty-four-hour creatinine clearance was determined and renal clearance studies of inulin and para-aminohippurate were done in a subset of 11 patients. Trough sitting blood pressures were reduced at the end of the first week in all groups. At weeks 4, 8, and 12 the reductions in systolic blood pressure/diastolic blood pressure averaged -11.9/-8.7, -10.8/-9.4, and -14.7/-12.1 mm Hg in patients with mild renal insufficiency and -7.7/-6.3, -13.1/-11.8, and -14.1/-10.6 mm Hg in patients with moderate-to-severe renal insufficiency. Creatinine clearance, glomerular filtration rate, and effective renal plasma flow were stable. Irbesartan was withdrawn in only five patients because of adverse clinical or laboratory experience. Hyperkalemia (>6 mEq/l) requiring discontinuation of irbesartan occurred in only one patient. Once-daily irbesartan given as monotherapy at dose of 150-300 mg or in combination with other antihypertensive drugs is effective in reducing blood pressure in hypertensive patients with chronic renal disease. Irbesartan regimens are well tolerated in all groups. In addition, the blood pressure-lowering effect of irbesartan is accompanied by a significant reduction in proteinuria in patients with chronic renal insufficiency. PMID:11486253

De Rosa, M L; de Cristofaro, A; Rossi, M; Baiano, A; Cardace, P; Albanese, L; Vigorito, C

2001-09-01

41

Irbesartan/amlodipine: a review of its use in adult patients with essential hypertension not adequately controlled with monotherapy.  

PubMed

Combination therapy is often required in patients with hypertension, and fixed-dose single-pill combinations have been shown to provide an easier regimen for patients, improving adherence. Irbesartan/amlodipine (Aprovasc®) is an angiotensin-receptor blocker/calcium-channel blocker fixed-dose single-pill combination, whose constituent drugs exert additive effects when coadministered. In two randomized, open-label, multicentre, phase III trials, fixed-dose combination therapy with irbesartan/amlodipine was more effective than continuation of irbesartan or amlodipine monotherapy in patients with hypertension not adequately controlled with initial irbesartan or amlodipine monotherapy; there was a significantly greater decrease from baseline in mean seated home systolic blood pressure (primary endpoint) with the fixed-dose combination. The fixed-dose combination was also associated with a greater decrease in mean seated home diastolic blood pressure and mean seated office systolic and diastolic blood pressure than monotherapy. The fixed-dose combination of irbesartan/amlodipine was well tolerated in these patients; most treatment-emergent adverse events were of mild or moderate severity. The most frequent adverse event was peripheral oedema, generally associated with amlodipine treatment. PMID:23516133

Garnock-Jones, Karly P

2013-04-01

42

Regression of hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed  

Microsoft Academic Search

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is a lipid-lowering and antioxidant agent. It suppresses the development of hypercholesterolemic atherosclerosis in rabbits. It is however not known if SDG would produce regression of atherosclerosis. The objectives of this study were to determine (i) if SDG produces regression of atherosclerosis; (ii) if regression is associated with reduction in serum lipids, oxidative stress

Kailash Prasad

2008-01-01

43

Irbesartan-mediated reduction of renal and cardiac damage in insulin resistant JCR : LA-cp rats  

PubMed Central

Background and purpose: Angiotensin II receptor antagonists (ARBs), originally developed for antihypertensive properties, have pleiotropic effects including direct vascular actions. We tested the hypothesis that the ARB irbesartan would be effective against micro- and macrovascular complications of the prediabetic metabolic syndrome using the obese, insulin-resistant JCR : LA-cp rat that exhibits micro- and macrovascular disease with ischaemic myocardial lesions and renal disease. Experimental approach: Obese male rats were treated with irbesartan (30 mg·kg?1·day?1, incorporated into chow) from 12 to 25 weeks of age. Key results: Irbesartan treatment caused no change in food intake or body weight. Fasting glycaemic control of the JCR : LA-cp rats was marginally improved, at the expense of increased plasma insulin levels (?50%). Fasting plasma triglycerides were marginally reduced (?25%), while cholesterol concentrations were unchanged. Elevated concentrations of adiponectin, monocyte chemotactic protein-1 and plasminogen activator inhibitor-1 were reduced along with severity of glomerular sclerosis. Macrovascular dysfunction (aortic hypercontractile response to noradrenergic stimulus and reduced endothelium-dependent relaxation) was improved and frequency of ischaemic myocardial lesions reduced (62%). Conclusions and implications: Irbesartan reduces markers of inflammation and prothombotic status, improves macrovascular function and reduces glomerular sclerosis and myocardial lesions in a model of the metabolic syndrome. Unlike pharmaceutical agents targeted on metabolic dysfunction, irbesartan reduced end-stage disease without major reduction of plasma lipids or insulin. The protective effects appear to be secondary to unknown intracellular mechanisms, probably involving signal transduction pathways. Understanding these would offer novel pharmaceutical approaches to protection against cardiovascular disease.

Russell, JC; Kelly, SE; Vine, DF; Proctor, SD

2009-01-01

44

Chlamydia pneumoniae and atherosclerosis  

Microsoft Academic Search

OBJECTIVETo review the literature for evidence that chronic infection withChlamydia pneumoniae is associated with atherosclerosis and acute coronary syndromes.DATA SOURCESmedline and Institute of Science and Information bibliographic databases were searched at the end of September 1998. Indexing terms used were chlamydi*, heart, coronary, and atherosclerosis. Serological and pathological studies published as papers in any language since 1988 or abstracts since

Y-K Wong; P J Gallagher; M E Ward

1999-01-01

45

Intracranial atherosclerosis following radiotherapy  

SciTech Connect

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

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

1988-07-01

46

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

47

Vinpocetine attenuates lipid accumulation and atherosclerosis formation.  

PubMed

Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis. PMID:23583194

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

2013-04-10

48

Geographical Pathology of Atherosclerosis,  

National Technical Information Service (NTIS)

The book presents results of investigations on the geographical pathology of atherosclerosis, conducted in various regions of the Soviet Union during the last 15 years. The methodology and program of study were developed on the initiative of the World Hea...

A. M. Vikhert B. S. Zhdanov E. E. Matova S. G. Aptekar

1987-01-01

49

T cells in atherosclerosis.  

PubMed

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

Tse, Kevin; Tse, Harley; Sidney, John; Sette, Alex; Ley, Klaus

2013-11-01

50

Diet and atherosclerosis.  

PubMed Central

Because of the statistical establishment of elevated blood lipids as a risk factor in the development of atherosclerotic heart disease, most of the attempts to regulate blood lipids by diet are centered on the fat in the diet. The levels of blood lipids and the course of experimental atherosclerosis can be affected by other dietary components such as type and amount of protein, carbohydrate, and nonnutritive fiber. Interaction among the dietary components further affects serum lipids and atherosclerosis.

Kritchevsky, D.

1976-01-01

51

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.

Bioengineering, Climb: C.

52

Rust and Rupture: Atherosclerosis  

Microsoft Academic Search

\\u000a This chapter provides an overview of the pathogenesis of atherosclerosis, and integrates the latest clinical guidelines and\\u000a trials into a concise and practical guide to cardiovascular risk reduction and the management of dyslipidemia. These measures\\u000a form the basis for a management strategy aimed at halting the progression of atherosclerosis, stabilizing rupture-prone plaques,\\u000a preventing arterial thrombosis, and improving cardiovascular prognosis.

Justin T. Saunders; Christie M. Ballantyne

53

Immune Mechanisms in Atherosclerosis  

Microsoft Academic Search

Abstract—Atherosclerosis is an inflammatory,disease. Its lesions are filled with immune,cells that can orchestrate and effect inflammatory responses. In fact, the first lesions of atherosclerosis consist of macrophages and T cells. Unstable plaques are particularly rich in activated immune cells, suggesting that they may initiate plaque activation. We have seen a rapid increase in the understanding of the mechanisms that govern

Goran K. Hansson; Lena Jonasson; Paul S. Seifert; Sten Stemme

2010-01-01

54

Atherosclerosis in alcoholics  

Microsoft Academic Search

A cohort of alcoholics who underwent a medico-legal autopsy during a 5-year period was compared with non-alcoholic controls who did not differ from the alcoholics in selection criteria. The degree of atherosclerosis in the coronary arteries and the aorta was examined. Alcoholic men and old women had a significantly lower degree of atherosclerosis in the coronary arteries, while the opposite

Jørgen L. Thomsen

1995-01-01

55

Spontaneous Atherosclerosis in Pigeons  

PubMed Central

The interpretation of metabolic studies related to early changes in spontaneous atherosclerosis has been hampered by the focal nature of the disease and by the lack of a well-defined model system of the disease process. Gross, histologic and ultrastructural observations of lesion development at the celiac bifurcation of the aorta in atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons are compared and discussed in terms of hemodynamics, muscular aggregation and altered metabolism of smooth muscle cells. Detailed knowledge of the morphologic sequence of events in lesion localization makes the celiac bifurcation in White Carneau and Show Racer pigeons a useful model for genetic comparisons of arterial wall metabolism and for investigating metabolic alterations occurring with atherogenesis. ImagesFig 9Fig 10Fig 1Fig 2Fig 10Fig 11Fig 3Fig 4Fig 12Fig 5Fig 6Fig 7Fig 8

Santerre, Robert F.; Wight, Thomas N.; Smith, Samuel C.; Brannigan, David

1972-01-01

56

Molecular imaging in atherosclerosis  

PubMed Central

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

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

2010-01-01

57

The UPR in atherosclerosis.  

PubMed

Multiple systemic factors and local stressors in the arterial wall can disturb the functions of endoplasmic reticulum (ER), causing ER stress in endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages during the initiation and progression of atherosclerosis. As a protective response to restore ER homeostasis, the unfolded protein response (UPR) is initiated by three major ER sensors: protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1? (IRE1?), and activating transcription factor 6 (ATF6). The activation of the various UPR signaling pathways displays a temporal pattern of activation at different stages of the disease. The ATF6 and IRE1? pathways that promote the expression of protein chaperones in ER are activated in ECs in athero-susceptible regions of pre-lesional arteries and before the appearance of foam cells. The PERK pathway that reduces ER protein client load by blocking protein translation is activated in SMCs and macrophages in early lesions. The activation of these UPR signaling pathways aims to cope with the ER stress and plays a pro-survival role in the early stage of atherosclerosis. However, with the progression of atherosclerosis, the extended duration and increased intensity of ER stress in lesions lead to prolonged and enhanced UPR signaling. Under this circumstance, the PERK pathway induces expression of death effectors, and possibly IRE1? activates apoptosis signaling pathways, leading to apoptosis of macrophages and SMCs in advanced lesions. Importantly, UPR-mediated cell death is associated with plaque instability and the clinical progression of atherosclerosis. Moreover, UPR signaling is linked to inflammation and possibly to macrophage differentiation in lesions. Therapeutic approaches targeting the UPR may have promise in the prevention and/or regression of atherosclerosis. However, more progress is needed to fully understand all of the roles of the UPR in atherosclerosis and to harness this information for therapeutic advances. PMID:23553213

Zhou, Alex X; Tabas, Ira

2013-04-04

58

Animal Models of Atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits and non-human primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. While not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable.

Getz, Godfrey S.; Reardon, Catherine A.

2012-01-01

59

Genes Involved in Atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a multifactorial disease that involves several genes and proteins. The purpose of this article is to focus on the arterial wall and to review lipoprotein receptors, growth factors, cytokines, chemokines, matrix metalloproteinases, adhesion molecules, and apoptosis genes and their involvement in atherogenesis.

Johanna Laukkanen; Seppo Ylä-Herttuala

2002-01-01

60

Inflammation in atherosclerosis  

Microsoft Academic Search

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

Peter Libby

2002-01-01

61

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.

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

2011-01-01

62

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

PubMed

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

63

Macrophage death and defective inflammation resolution in atherosclerosis  

Microsoft Academic Search

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

Ira Tabas

2009-01-01

64

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

65

Eplerenone inhibits atherosclerosis in nonhuman primates.  

PubMed

Aldosterone may be involved in the pathogenesis of atherosclerosis. We investigated the effect of eplerenone, a selective mineralocorticoid receptor blocker, on atherosclerosis in monkeys fed a high-cholesterol diet. Monkeys fed a high-cholesterol diet for 9 months were divided into 3 groups: those treated with a low dose of eplerenone (30 mg/kg per day); those treated with a high dose of eplerenone (60 mg/kg per day); and the placebo-treated group. The normal group consisted of monkeys fed a normal diet. There were no significant differences in blood pressure and cholesterol levels between the placebo- and eplerenone-treated groups. On the other hand, monocyte chemoattractant protein-1 and malondialdehyde-modified LDL were significantly higher in the placebo-treated group than in the normal group, whereas they were suppressed in the eplerenone-treated groups. The ratio of intimal volume to total volume by intravascular ultrasound analysis imaging of the aortas was dose-dependently lower in the eplerenone-treated groups than in the placebo-treated group. Acetylcholine-induced vasorelaxation was significantly weaker in the placebo-treated group than in the normal group, but the vasorelaxation was strengthened in the eplerenone-treated groups. A significant upregulation of angiotensin-converting enzyme activity was observed in the placebo-treated group, but the activity was suppressed in the eplerenone-treated groups. In conclusion, eplerenone may strengthen the endothelium-dependent relaxation and suppress angiotensin-converting enzyme activity in the vasculature, thus preventing the development of atherosclerosis in nonhuman primates. PMID:16203870

Takai, Shinji; Jin, Denan; Muramatsu, Michiko; Kirimura, Kazuyoshi; Sakonjo, Hiroshi; Miyazaki, Mizuo

2005-10-03

66

Cardiac and Renal Protective Effects of Irbesartan via Peroxisome Proliferator-Activated Receptor?-Hepatocyte Growth Factor Pathway Independent of Angiotensin II Type 1a Receptor Blockade in Mouse Model of Salt-Sensitive Hypertension  

PubMed Central

Background “Aldosterone breakthrough” observed in patients receiving long?term treatment with angiotensin blockade is strongly associated with increased risk of left ventricular hypertrophy, poor exercise capacity, refractory proteinuria, and declining glomerular filtration rate through the profibrotic actions of aldosterone. To overcome aldosterone breakthrough, we examined the additional organ?protective actions of irbesartan, because irbesartan is an angiotensin II type 1 receptor (AT1R) blocker (ARB) with peroxisome proliferator?activated receptor (PPAR)? agonistic effects, which mediate organ?protective effects independent of AT1R blockade. In this study, we examined the organ?protective effects of irbesartan in a salt?sensitive hypertension model using AT1aR knockout mice. Methods and Results Aldosterone and 1% NaCl treatment resulted in a significant increase in severe cardiac and renal fibrosis. Irbesartan, but not losartan, significantly reduced renal fibrosis, glomerular injury through inhibition of macrophage infiltration, epithelial–mesenchymal transition, and oxidative stress. Similarly, cardiac fibrosis and myocyte hypertrophy were decreased by irbesartan, but not losartan, treatment, associated with a significant reduction in oxidative stress. Importantly, anti–hepatocyte growth factor (HGF) neutralizing antibody and a PPAR? antagonist (GW9662) attenuated these organ?protective effects of irbesartan. HGF protein level was increased by irbesartan, especially in the kidney and heart, while GW9662 treatment inhibited the increase in HGF level. Conclusions In this study, we showed that irbesartan, which has not only AT1aR?blocking effects, but also PPAR? agonistic effects accompanied by HGF expression, inhibited organ damage by aldosterone and salt treatment. Second?generation ARBs such as irbesartan, which has the dual actions of AT1R blockade and PPAR? activation, may have clinical value for the treatment of hypertensive patients with aldosterone breakthrough.

Kusunoki, Hiroshi; Taniyama, Yoshiaki; Rakugi, Hiromi; Morishita, Ryuichi

2013-01-01

67

Gene therapy for atherosclerosis  

Microsoft Academic Search

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

D. J. Rader

1997-01-01

68

Lipid peroxides and atherosclerosis  

Microsoft Academic Search

Plasma lipid peroxide concentrations were measured in 100 patients with occlusive arterial disease proved angiographically (50 patients with ischaemic heart disease, 50 with peripheral arterial disease) and compared with values in 75 control patients with no clinical evidence of atherosclerosis. Lipid peroxide concentrations were significantly higher in patients both with ischaemic heart disease (median 4.37 mumol\\/l (interquartile range 3.85-5.75 mumol\\/l);

M. D. Stringer; P. G. Görög; A. Freeman; V. V. Kakkar

1989-01-01

69

Comparative Cost Effectiveness of Angiotensin II Receptor Blockers in a US Managed Care Setting: Olmesartan Medoxomil Compared with Losartan, Valsartan, and Irbesartan  

Microsoft Academic Search

Objective: To compare the cost effectiveness of the angiotensin II receptor blockers (ARBs) olmesartan medoxomil, losartan, valsartan and irbesartan for the treatment of hypertension, from the perspective of a US managed care setting. Methods: The evaluation was based on a recently completed, prospective, randomised, double-blind clinical trial comparing the antihypertensive efficacy of these agents. Differences in diastolic blood pressure reductions

W. Robert Simons

2003-01-01

70

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.

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

2012-01-01

71

Long-Term Effects of Irbesartan Treatment and Smoking on Nucleic Acid Oxidation in Patients With Type 2 Diabetes and Microalbuminuria  

PubMed Central

OBJECTIVE We tested whether long-term treatment with the angiotensin II receptor antagonist irbesartan reduces nucleic acid oxidation in patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS The Irbesartan in Patients With Type 2 Diabetes and Microalbuminuria (IRMA 2) study was a 2-year multicenter randomized double-blind trial comparing irbesartan (150 and 300 mg once daily) with placebo. We studied a subgroup of 50 patients where urine samples were available for analysis of albumin and the oxidatively modified guanine nucleosides 8-oxo-7,8-dihydro-2?-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). RESULTS During the 2-year trial, no significant differences in 8-oxodG and 8-oxoGuo excretions between placebo and irbesartan treatment were seen. 8-oxodG and albumin excretion decreased with time (P = 0.0004 and P < 0.0001, respectively), whereas treatment-related differences were shown for albumin excretion (P = 0.0008) only, as previously reported. Important secondary findings were significant associations between changes in 8-oxodG excretion and changes in albumin excretion and glycated hemoglobin (HbA1c). During the study period, 8-oxodG excretion decreased by 3 and 26% in smokers and nonsmokers, respectively (P = 0.015), and urinary albumin excretion decreased 22% in smokers and 58% in nonsmokers (P = 0.011). CONCLUSIONS Irbesartan treatment was not significantly more effective than placebo in reducing nucleic acid oxidation. The results indicate that DNA oxidation in diabetes patients is reduced by various components in the treatment of diabetes where glycemic control seems to be important and addition of angiotensin II receptor antagonists does not lead to any substantial additional reduction. Furthermore, the reductions in DNA oxidation and albumin excretion seem to be counteracted by smoking.

Broedbaek, Kasper; Henriksen, Trine; Weimann, Allan; Petersen, Morten; Andersen, Jon T.; Afzal, Shoaib; Jimenez-Solem, Espen; Persson, Frederik; Parving, Hans-Henrik; Rossing, Peter; Poulsen, Henrik E.

2011-01-01

72

Ectasia and Severe Atherosclerosis  

PubMed Central

To date, there has been no convincing evidence for an association between Chlamydia pneumoniae or Helicobacter pylori and ectasia. In this case-control study, we have investigated the association of H. pylori and C. pneumoniae seropositivity with ectasia, severe coronary atherosclerosis, and normal vessels, which were so classified by coronary angiography. We have also evaluated the influence of these infections on inflammatory markers such as high-sensitive C-reactive protein (hsCRP) and interleukin 6 (IL-6). Of the 796 patients undergoing coronary angiography for suspected ischemic heart disease, 244 patients were recruited. Of these, 91 had normal vessels, 88 had 3 or more obstructed vessels, and 65 had ectatic vessels without atherosclerosis. Eighty-seven atherosclerotic patients (98.9%) were positive for C. pneumoniae IgG, as were 64 ectatic patients (98.5%) and 76 controls (83.5%) (P < 0.001). Forty-two atherosclerotic patients (47.7%) were positive for C. pneumoniae IgM, as were 43 ectatic patients (66.2%) and 43 controls (47.3%) (P = 0.036). Seventy-two atherosclerotic patients (81.8%) were positive for H. pylori IgA, as were 26 ectatic patients (40.0%) and 44 controls (48.4%) (P < 0.001). High-sensitive CRP levels were significantly higher in ectatic patients (5.639 mg/L) than in controls (4.390 mg/L) (P = 0.032), and IL-6 levels were significantly higher in atherosclerotic patients (33.92 U/L) than in controls (14.01 U/L) (P < 0.001). Interleukin-6 levels were higher in H. pylori seropositive patients, and hsCRP levels were higher in C. pneumoniae seropositive patients, when compared with seronegatives. We suggest that, as in atherosclerosis, C. pneumoniae infection is related to ectasia, with raised CRP levels.

Adiloglu, Ali K.; Can, Rabia; Nazli, Cem; Ocal, Ahmet; Ergene, Oktay; Tinaz, Gulgun; Kisioglu, Nesimi

2005-01-01

73

[Atherosclerosis, alcohol and diabetes].  

PubMed

Diabetes is a known risk factor of atherosclerosis, moderate consumption of alcohol was reported to reduce the cardiovascular morbidity and mortality. This review presents information on the possible mechanisms of the antiatherogenic effect of alcohol and data of the effect of moderate alcohol drinking on the prevention of cardiovascular diseases. Red wine contains polyphenols with an antioxidant effect, alcohol is metabolized to acetaldehyde which was proved to inhibit the formation of advanced glycation endproducts (AGE) and lipoprotein oxidation. Diabetic patients may benefit from moderate consumption of alcohol beverages only if the risk of hypoglycemia is safely excluded. PMID:12132355

Bartos, V

2002-06-01

74

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.

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

2012-01-01

75

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

76

A randomised, double-blind comparison of the angiotensin II receptor antagonist, irbesartan, with the full dose range of enalapril for the treatment of mild-to-moderate hypertension  

Microsoft Academic Search

Objective: To compare the anti-hypertensive efficacy, safety, and tolerability of irbesartan with those of the full dose range of enalapril in patients with mild-to-moderate hypertension. Design and methods: A total of 200 patients were randomised to irbesartan 75 mg or enalapril 10 mg (once daily). Doses were doubled at Weeks 4 and\\/or 8 if seated diastolic blood pressure (DBP) was

A Mimran; L Ruilope; L Kerwin; M Nys; D Owens; K Kassler-Taub; M Osbakken

1998-01-01

77

Molecular biology of atherosclerosis.  

PubMed

At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-? and related family members leading to activation of NF-?B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world. PMID:23899566

Hopkins, Paul N

2013-07-01

78

Telomeres and atherosclerosis.  

PubMed

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

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

2012-11-01

79

Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice.  

PubMed

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

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

2013-05-31

80

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.

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

2012-01-01

81

Knockdown of mTOR by lentivirus?mediated RNA interference suppresses atherosclerosis and stabilizes plaques via a decrease of macrophages by autophagy in apolipoprotein E?deficient mice.  

PubMed

Atherosclerotic plaque destabilization and rupture leads to acute coronary syndromes which cause serious damage to human health worldwide. However, there is currently a lack of efficient therapeutic methods. Mammalian target of rapamycin (mTOR) has been suggested to be involved in the development of atherosclerotic plaques and serves as a therapeutic target. The present study was performed to determine whether RNA interference (RNAi) of mTOR in vivo by LV?mediated small hairpin RNA (shRNA) was capable of inhibiting the progression of atherosclerotic plaques. LV?mediated shRNA against mTOR (LV?shmTOR) was designed and obtained. Male apolipoprotein E?deficient mice were fed a high?fat diet and a constrictive collar was placed around the right carotid arteries of these mice to induce plaque formation. Eight weeks after surgery, mice were randomly divided into the mTOR RNA interference (LV?shmTOR) group, receiving treatment with LV?mTOR?shRNA; the LV?shCON group, receiving treatment with LV?non?specific?shRNA; and the control group, receiving treatment with phosphate?buffered saline. Following transfection, the mice were sacrificed to evaluate the effects of mTOR expression silencing on atherosclerosis. Transfection of LV?mTOR?shRNA markedly inhibited the mRNA and protein expression levels. Knockdown of mTOR ameliorated dysregulated blood lipid metabolism and stabilized aortic atherosclerotic plaques by decreasing the plaque area and increasing the fibrous cap and cap?to?core ratio. Furthermore, macrophages were decreased by silencing mTOR in atherosclerotic plaques. In addition, western blot analysis revealed that the knockdown of mTOR increased autophagy?related protein 13 (Atg13) dephosphorylation and light chain 3?I/light chain 3?II (LC3?I/LC3?II) ratios, both of which were associated with a high activity of autophagy, suggesting an increase of autophagy in atherosclerotic plaques. Moreover, genes including matrix metalloproteinase 2, monocyte chemoattractant protein 1 and tissue factor, which promote plaque instability, were downregulated by silencing mTOR. These results demonstrate that LV?mediated mTOR silencing by RNAi treatment induces macrophage autophagy and is a potential strategy for the treatment of atherosclerotic plaques. PMID:24043133

Wang, Xiaochuang; Li, Lingxia; Li, Manxiang; Dang, Xiaoyan; Wan, Lin; Wang, Ni; Bi, Xiaoju; Gu, Changwei; Qiu, Suijuan; Niu, Xiaolin; Zhu, Xinye; Wang, Lina

2013-09-12

82

Extracellular phospholipases in atherosclerosis.  

PubMed

Phospholipases A2 (PLA2) are a family of enzymes that catalyze the hydrolysis of the sn-2 ester bond of glycerophospholipids liberating lysophospholipids and free fatty acids; important second messengers involved in atherogenesis. Plasma PAF-acetylhydrolase (PAF-AH) or Lp-PLA2 is a Ca(2+)-independent PLA2 which is produced by monocyte-derived macrophages and by activated platelets, and circulates in plasma associated with lipoproteins. PAF-AH catalyzes the removal of the acetyl/short acyl group at the sn-2 position of PAF and oxidized phospholipids produced during inflammation and oxidative stress. In humans, PAF-AH is mainly associated with small dense LDL and to a lesser extent with HDL and with lipoprotein(a). PAF-AH is N-glycosylated prior to secretion which diminishes its association with HDL raising the question of its distribution between the proatherogenic LDL vs the antiatherogenic HDL. Hypercholesterolemic patients have higher plasma PAF-AH activity which is reduced upon hypolipidemic therapy. PAF-AH specific inhibitor darapladib stabilizes human and swine plaques, therefore challenging the antiatherogenic potential of PAF-AH shown in small animal models. Among secreted PLA2s (sPLA2), the group X sPLA2 (PLA2GX), due to its very high activity towards phosphatidylcholine the main phospholipid of LDL, became an attractive target in atherosclerosis. We showed that PLA2GX is present in human atherosclerotic lesions and that the PLA2GX-phospholipolysed LDL triggers human macrophage-foam cell formation. In contrast to other sPLA2s, including group IB, IIA and V, PLA2GX can efficiently hydrolyze PAF present in lipoproteins or vesicles indicating that PLA2GX may be a novel player in PAF regulation upon inflammatory processes. By a genetic approach we uncovered a relatively rare polymorphism (Arg38Cys) which produces a catalytically inactive PLA2GX; although no association was observed with cardiovascular risk factors in the AtheroGene study, this result should be replicated in cohorts of other inflammatory diseases. We anticipate that mores studies will be necessary to sort out the exact role of extracellular PLA2 family members in atherosclerosis initiation and progression. PMID:20153800

Karabina, Sonia-Athina; Gora, Sarah; Atout, Rajai; Ninio, Ewa

2010-02-12

83

Calpain and atherosclerosis.  

PubMed

This review highlights the pro-atherogenic roles of Ca(2+)-sensitive intracellular protease calpains. Among more than ten species of calpain isozymes, µ- and m-calpains have been characterized most extensively. These two isozymes are ubiquitously expressed in mammalian tissues, including blood vessels, and tightly regulate functional molecules in the vascular component cells through limited proteolytic cleavage. Indeed, previous cell-based experiments showed that calpains play significant roles in nitric oxide production in vascular endothelial cells (ECs), maintenance of EC barrier function and angiogenesis for maintaining vascular homeostasis. Recently, we demonstrated that modified-low density lipoprotein (LDL)-induced m-calpain causes hyperpermeability in ECs, leading to the infiltration of monocytes/macrophages and plasma lipids into the intimal spaces (Miyazaki T. et al., Circulation. 2011; 124: 2522-2532). Calpains also mediate oxidized LDL-induced apoptotic death in ECs. In monocytes/macrophages, calpains induce proteolytic degradation of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1), which results in impaired cholesterol efflux and subsequent macrophage foam cell formation. In vascular smooth muscle cells, calpains may be involved in the conversion from contractile phenotype to proliferative phenotype. In hepatocytes, calpains disrupt the biogenesis of high-density lipoprotein via proteolytic degradation of ABCA1. Thus, calpains may serve as novel candidate molecular targets for control of atherosclerosis. PMID:23171729

Miyazaki, Takuro; Koya, Takayuki; Kigawa, Yasuyoshi; Oguchi, Tatsunori; Lei, Xiao-Feng; Kim-Kaneyama, Joo-ri; Miyazaki, Akira

2012-11-22

84

[Chronic inflammation and atherosclerosis].  

PubMed

The increasing gain of knowledge regarding the mechanistic details of the pathogenesis of chronic inflammatory diseases e. g. of rheumatic origin, chronic viral infections and atherosclerosis have revealed in conjunction with detailed insights in acute inflammation interesting similarities and differences. Cytokines such as IL-1 and tumour necrosis factor-? are proximal components of inflammatory cascades of systemic mediators activating the endothelium which leads to an endothelial dysfunction and moreover alter the balance within lymphocytic subpopulations containing distinct arsenals of secretory mediators such as interferons, interleukins and chemokines. Proinflammatory lymphocyte subtypes are TH1 und TH17 cells whereas Treg and TH2 cells are anti-inflammatory opponents. Since several years, interleukin-1- and TNF-antagonists have expanded the spectrum of drugs against rheumatic diseases and are currently studied in the setting of cardiovascular prevention with positive results on surrogate parameters. On the other hand efforts are undertaken to test the hypothesis if the pleiotropic effects of statins may have a positive influence on rheumatoid arthritis. PMID:24006166

von Hundelshausen, P; Weber, C

2013-09-04

85

Proteomic Biomarkers of Atherosclerosis.  

PubMed

SUMMARY: Biomarkers provide a powerful approach to understanding the spectrum of cardiovascular diseases. They have application in screening, diagnostic, prognostication, prediction of recurrences and monitoring of therapy. The "omics" tool are becoming very useful in the development of new biomarkers in cardiovascular diseases. Among them, proteomics is especially fitted to look for new proteins in health and disease and is playing a significant role in the development of new diagnostic tools in cardiovascular diagnosis and prognosis. This review provides an overview of progress in applying proteomics to atherosclerosis. First, we describe novel proteins identified analysing atherosclerotic plaques directly. Careful analysis of proteins within the atherosclerotic vascular tissue can provide a repertoire of proteins involved in vascular remodelling and atherogenesis. Second, we discuss recent data concerning proteins secreted by atherosclerotic plaques. The definition of the atheroma plaque secretome resides in that proteins secreted by arteries can be very good candidates of novel biomarkers. Finally we describe proteins that have been differentially expressed (versus controls) by individual cells which constitute atheroma plaques (endothelial cells, vascular smooth muscle cells, macrophages and foam cells) as well as by circulating cells (monocytes, platelets) or novel biomarkers present in plasma. PMID:19578499

Vivanco, F; Padial, L R; Darde, V M; de la Cuesta, F; Alvarez-Llamas, G; Diaz-Prieto, Natacha; Barderas, M G

2008-03-12

86

The neglected coronary atherosclerosis.  

PubMed

A study of the natural history of coronary heart disease by means of gross inspection and light microscopy, carried out on 640 subjects aged 1-50 years who had died of violent accidents, revealed a grossly neglected coronary atherosclerosis. It included fibromuscular plaques, intimal necrotic areas and incorporated microthrombi present in the longitudinally opened main coronary arteries but not visible to the naked eye, and some atherosclerotic lesions visible to the naked eye but present in branch vessels unopened or not removed during routine autopsy. There were approximately 500 grossly neglected intimal necrotic areas and approximately 120 grossly neglected incorporated microthrombi; from a total of 809 atherosclerotic plaques 261 (32%) were grossly neglected. The topographic distribution and the number of neglected and non-neglected atherosclerotic plaques, in successive age groups, were analyzed. A small subsample, including 32 patients 52-79 years old, dead of coronary heart disease, was used to demonstrate the importance of the detection of obstructive atherosclerotic lesions in some usually unopened or not removed branch vessels for a realistic anatomo-clinic-cardioangiographic and ECG correlation. PMID:6882496

Velican, C; Velican, D

1983-06-01

87

Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis  

PubMed Central

Of the multiple sources of reactive oxygen species (ROS) in the blood vessel, NADPH oxidases are the primary source. Whereas several studies have implicated NADPH oxidases in the initiation of atherosclerosis, their roles in disease progression are incompletely understood. Our objective was to determine the potential clinical relevance of inhibiting NADPH oxidase in established atherosclerosis. Using a hypercholesteremic murine model of atherosclerosis (ApoE?/?/LDLR?/? (AS) mice on normal chow diet), we first established a time-dependent relationship between superoxide levels and lesion size in AS mice. Next, we identified NADPH oxidase as the primary source of ROS in atherosclerotic lesions. Treatment of aortic segments from AS mice with apocynin, which interferes with NADPH oxidase activation in part by preventing translocation of the subunit p47phox, significantly reduced superoxide levels. Moreover, addition of apocynin to the drinking water of AS mice produced a decrease in lesion size as compared to untreated AS mice, with the effect most pronounced in the thoracoabdominal aorta but absent from the aortic arch. Granulocyte function in AS+apocynin mice was suppressed, confirming efficacy of apocynin treatment. We conclude that apocynin attenuates the progression of atherosclerosis in hypercholesterolemic mice, potentially by its ability to inhibit generation of superoxide by NADPH oxidase.

Kinkade, Kara; Streeter, Jennifer; Miller, Francis J.

2013-01-01

88

Endoplasmic reticulum stress and atherosclerosis  

PubMed Central

Atherosclerosis and related cardiovascular diseases represent one of the greatest threats to human health worldwide. Despite important progress in prevention and treatment, these conditions still account for one third of all deaths annually. Often presented together with obesity, insulin resistance and type 2 diabetes, these chronic diseases are strongly influenced by pathways that lie at the interface of chronic inflammation and nutrient metabolism. Here I discuss recent advances in the study of endoplasmic reticulum stress as one mechanism that links immune response with nutrient sensing in the pathogenesis of atherosclerosis and its complications.

Hotamisligil, Gokhan S

2010-01-01

89

Estrogen replacement therapy, atherosclerosis, and vascular function  

Microsoft Academic Search

There is strong evidence from both human and nonhuman primate studies supporting the conclusion that estrogen deficiency increases the progression of atherosclerosis. More controversial is the conclusion that postmenopausal estrogen replacement inhibits the progression of atherosclerosis. Estrogen treatment of older women (.65 years) with pre-existing coronary artery atherosclerosis had no beneficial effects. In contrast, estrogen treatment of younger postmenopausal women

Tomi S. Mikkola; Thomas B. Clarkson

90

Intracranial Atherosclerosis: Incidence, Diagnosis and Treatment  

Microsoft Academic Search

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

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

2005-01-01

91

Oxidative Stress, AntioxidantVitamins, and Atherosclerosis  

Microsoft Academic Search

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

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

2003-01-01

92

Macrophage autophagy plays a protective role in advanced atherosclerosis.  

PubMed

In advanced atherosclerosis, macrophage apoptosis coupled with defective phagocytic clearance of the apoptotic cells (efferocytosis) promotes plaque necrosis, which precipitates acute atherothrombotic cardiovascular events. Oxidative and endoplasmic reticulum (ER) stress in macrophages are important causes of advanced lesional macrophage apoptosis. We now show that proapoptotic oxidative/ER stress inducers trigger another stress reaction in macrophages, autophagy. Inhibition of autophagy by silencing ATG5 or other autophagy mediators enhances apoptosis and NADPH oxidase-mediated oxidative stress while at the same time rendering the apoptotic cells less well recognized by efferocytes. Most importantly, macrophage ATG5 deficiency in fat-fed Ldlr(-/-) mice increases apoptosis and oxidative stress in advanced lesional macrophages, promotes plaque necrosis, and worsens lesional efferocytosis. These findings reveal a protective process in oxidatively stressed macrophages relevant to plaque necrosis, suggesting a mechanism-based strategy to therapeutically suppress atherosclerosis progression and its clinical sequelae. PMID:22445600

Liao, Xianghai; Sluimer, Judith C; Wang, Ying; Subramanian, Manikandan; Brown, Kristy; Pattison, J Scott; Robbins, Jeffrey; Martinez, Jennifer; Tabas, Ira

2012-03-22

93

Gene Expression Phenotypes of Atherosclerosis  

Microsoft Academic Search

Objective—Fulfilling the promise of personalized medicine by developing individualized diagnostic and therapeutic strategies for atherosclerosis will depend on a detailed understanding of the genes and gene variants that contribute to disease susceptibility and progression. To that end, our group has developed a nonbiased approach congruent with the multigenic concept of complex diseases by identifying gene expression patterns highly associated with

David Seo; Tao Wang; Holly Dressman; Edward E. Herderick; Edwin S. Iversen; Chunming Dong; Korkut Vata; Carmelo A. Milano; Fabio Rigat; Jennifer Pittman; Joseph R. Nevins; Mike West; Pascal J. Goldschmidt-Clermont

2010-01-01

94

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...

95

IDL, VLDL, chylomicrons and atherosclerosis  

Microsoft Academic Search

In humans with the lipoprotein lipase deficiency disorder large amounts of chylomicrons and large very low-density lipoprotein (VLDL) accumulate in plasma. In spite of this, atherosclerosis does not seem to develop at an accelerated rate, suggesting that these lipoproteins do not promote atherogenesis. In humans with dysbetalipoproteinemia remnant lipoproteins (intermediate density lipoprotein (IDL) plus B-VLDL) accumulate in plasma and these

B. G. Nordestgaard; A. Tybjærg-Hansen

1992-01-01

96

PPAR? in atherosclerosis and inflammation  

PubMed Central

Summary Peroxisome proliferators-activated receptor (PPAR)? is a nuclear receptor activated by natural ligands such as fatty acids as well as by synthetic ligands such as fibrates currently used to treat dyslipidemia. PPAR? regulates the expression of genes encoding proteins that are involved in lipid metabolism, fatty acid oxidation and glucose homeostasis, thereby improving markers for atherosclerosis and insulin resistance. In addition, PPAR? exerts anti-inflammatory effects both in the vascular wall and the liver. Here we provide an overview of the mechanisms through which PPAR? affects the initiation and progression of atherosclerosis, with emphasis on the modulation of atherosclerosis-associated inflammatory responses. PPAR? activation interferes with early steps in angiogenesis by reducing leukocyte adhesion to activated endothelial cells of the arterial vessel wall and inhibiting subsequent transendothelial leukocyte migration. In later stages of atherosclerosis, evidence suggests activation of PPAR? inhibits the formation of macrophage foam cells by regulating expression of genes involved in reverse cholesterol transport, formation of reactive oxygen species (ROS), and associated lipoprotein oxidative modification among others. Furthermore, PPAR? may increase the stability of atherosclerotic plaques and limit plaque thrombogenicity. These various effects may be linked to the generation of PPAR? ligands by endogenous mechanisms of lipoprotein metabolism. In spite of this dataset, other reports implicate PPAR? in responses such as hypertension and diabetic cardiomyopathy. Although some clinical trials data with fibrates suggest that fibrates may decrease cardiovascular events, other studies have been less clear, at least in the presence of concomitant statin therapy. Independent of the clinical effects of currently used purported PPAR? agonists, extensive data establishes the importance of PPAR? in the transcriptional regulation of lipid metabolism, atherosclerosis and inflammation.

Zandbergen, Fokko; Plutzky, Jorge

2007-01-01

97

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

98

Effects of irbesartan on gene expression revealed by transcriptome analysis of left atrial tissue in a porcine model of acute rapid pacing in vivo.  

PubMed

BACKGROUND: Atrial fibrillation (AF) is characterized by electrical and structural remodeling of the atria with atrial fibrosis being one hallmark. Angiotensin II (AngII) is a major contributing factor and blockage of its type I receptor (AT1R) prevents remodeling to some extent. Here we explored the effects of the AT1R antagonist irbesartan on global gene expression and profibrotic signaling pathways after induction of rapid atrial pacing (RAP) in vivo in pigs. METHODS AND RESULTS: Microarray-based RNA profiling was used to screen left atrial (LA) tissue specimens for differences in atrial gene expression in a model of acute RAP. RAP caused an overall expression profile that reflected AngII-induced ROS production, tissue remodeling, and energy depletion. Of special note, the mRNA levels of EDN1, SGK1, and CTGF encoding pro-endothelin, stress- and glucocorticoid activated kinase-1, and of connective tissue growth factor were identified to be significantly increased after 7h of rapid pacing. These specific expression changes were additionally validated by RT-qPCR or immunoblot analyses in LA, RA, and partly in LV samples. All RAP-induced differential gene expression patterns were partially attenuated in the presence of irbesartan. Similar results were obtained after RAP of HL-1 cardiomyocytes in vitro. Furthermore, exogenously added endothelin-1 (ET1) induced CTGF expression concomitant to the transcriptional activation of SGK1 in HL-1 cells. CONCLUSIONS: RAP provokes substantial changes in atrial and ventricular myocardial gene expression that could be partly reversed by irbesartan. ET1 contributes to AF-dependent atrial fibrosis by synergistic activity with AngII to stimulate SGK1 expression and enhance phosphorylation of the SGK1 protein which, in turn, induces CTGF. The latter has been consistently associated with tissue fibrosis. These findings suggest ETR antagonists as being beneficial in AF treatment. PMID:23414741

Chilukoti, Ravi Kumar; Mostertz, Jörg; Bukowska, Alicja; Aderkast, Christoph; Felix, Stephan B; Busch, Matthias; Völker, Uwe; Goette, Andreas; Wolke, Carmen; Homuth, Georg; Lendeckel, Uwe

2013-02-12

99

Detection of presymptomatic atherosclerosis: a current perspective.  

PubMed

Atherosclerosis, the pathological process underlying myocardial infarction, stroke and other occlusive vascular disease, is the major cause of death in the Western world. The development of techniques to accurately and reproducibly detect and measure the early changes of atherosclerosis and/or to identify subjects at highest cardiovascular risk may aid in the development of prevention strategies and facilitate a decrease in morbidity and mortality from atherosclerosis. Increasing understanding of the pathophysiology of early atherosclerosis has allowed the development of a number of potential methods for the assessment of the early stages of atherosclerosis in humans. These include techniques for assessing early structural changes in the coronary arteries with electron-beam computed tomography and magnetic resonance imaging. External vascular ultrasound has also been used to image other circulations as a surrogate marker for coronary atherosclerosis, e.g. the measurement of carotid artery intima-media thickness. Early functional changes of atherosclerosis have also been described many years before the development of structural changes. A number of techniques have been developed to measure endothelial dysfunction, one of the earliest changes of atherosclerosis, including non-invasive measurement of endothelial function using external vascular ultrasound. A variety of serum markers have also been described, and may be useful markers of atherosclerosis. We discuss some of the more promising techniques for the detection of early, presymptomatic atherosclerosis. PMID:10545314

Adams, M R; Celermajer, D S

1999-11-01

100

Atherosclerosis in Juvenile Idiopathic Arthritis  

PubMed Central

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

Jednacz, Ewa; Rutkowska-Sak, Lidia

2012-01-01

101

Atherosclerosis in juvenile idiopathic arthritis.  

PubMed

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

Jednacz, Ewa; Rutkowska-Sak, Lidia

2012-08-13

102

Immunity, atherosclerosis and cardiovascular disease.  

PubMed

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

Frostegård, Johan

2013-05-01

103

Immunity, atherosclerosis and cardiovascular disease  

PubMed Central

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

2013-01-01

104

Plasmacytoid Dendritic Cells in Atherosclerosis  

PubMed Central

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

Doring, Yvonne; Zernecke, Alma

2012-01-01

105

Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: A sub analysis of the Treat to Target post authorization survey. Prospective observational, two armed study in 14,200 patients  

Microsoft Academic Search

OBJECTIVES: The metabolic syndrome is a cluster of cardiovascular risk factors leading to an increased risk for the subsequent development of diabetes and cardiovascular morbidity and mortality. Blocking the renin-angiotensin system has been shown to prevent cardiovascular disease and delay the onset of diabetes. Irbesartan is an angiotensin receptor blocker (ARB) which has been shown to possess peroxisome proliferator-activated receptor

Ulrich Kintscher; Peter Bramlage; W Dieter Paar; Martin Thoenes; Thomas Unger

2007-01-01

106

Immune Response to Lipoproteins in Atherosclerosis  

PubMed Central

Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL) has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

Samson, Sonia; Mundkur, Lakshmi; Kakkar, Vijay V.

2012-01-01

107

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

NASA Astrophysics Data System (ADS)

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 ?(I 3-) respectively, confirmed the presence of I 3- 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.

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

2011-09-01

108

Novel markers of inflammation in atherosclerosis  

Microsoft Academic Search

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

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

2008-01-01

109

Aliskiren Reduces Blood Pressure and Suppresses Plasma Renin Activity in Combination With a Thiazide Diuretic, an Angiotensin-Converting Enzyme Inhibitor, or an Angiotensin Receptor Blocker  

Microsoft Academic Search

untreated; median (interquartile range); aliskiren and hydrochlorothiazide: 0.4 (0.2 to 1.1) versus 0.7 (0.5 to 1.3); ramipril and aliskiren: 0.5 (0.3 to 0.9) versus 0.6 (0.5 to 0.8); irbesartan and aliskiren: 0.4 (0.2 to 0.9) versus 0.6 (0.4 to 0.9)). These results suggest that renin inhibition with aliskiren in these combinations increases renin-angiotensin system suppression, improves 24-hour blood pressure control,

Eoin O'Brien; John Barton; Juerg Nussberger; David Mulcahy; Chris Jensen; Patrick Dicker; Alice Stanton

110

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

111

Earlobe crease and atherosclerosis. An autopsy study.  

PubMed

The association between earlobe crease (ELC) and coronary and aortic atherosclerosis in 100 autopsied men ranging in age from 50 to 79 years, who died free of vascular diseases or related conditions, was studied in conjunction with blood pressure and serum total cholesterol (TC) levels. Earlobe crease was graded and defined as groups 1, 2, and 3 according to the depth and length in both ears. The extent of atherosclerosis in the coronary arteries and aortas was visually graded. Coronary atherosclerosis was significantly more severe in group 3 in all the decades examined than in groups 1 or 2. Aortic atherosclerosis in group 3 was significantly greater than in group 1 in all the decades examined, and was greater than in group 2 in the seventh and eighth decades. The TC level was significantly higher in group 3 than in groups 1 or 2 except in the sixth decade. Multivariate regression analyses demonstrated that the degree of ELC was dependent on the extent of coronary and aortic atherosclerosis, but was independent of age. Conversely, the extent of coronary atherosclerosis was dependent on the degree of ELC, but was independent of age. The extent of aortic atherosclerosis was, however, dependent not only on the appearance of ELC and TC, but on age. It is thus concluded that ELC provides a significant external marker for atherosclerosis and may reflect a persistent overload of atherosclerosis risk factors, such as TC. PMID:2095754

Ishii, T; Asuwa, N; Masuda, S; Ishikawa, Y; Shimada, K; Takemoto, S

1990-08-01

112

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

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

2000-01-01

113

Vascular extracellular matrix in atherosclerosis.  

PubMed

The extracellular matrix (ECM) is an essential component of the human body that is responsible for the proper function of various organs. Changes in the ECM have been implicated in the pathogenesis of several cardiovascular conditions including atherosclerosis, restenosis, and heart failure. Matrix components, such as collagens and noncollagenous proteins, influence the function and activity of vascular cells, particularly vascular smooth muscle cells and macrophages. Matrix proteins have been shown to be implicated in the development of atherosclerotic complications, such as plaque rupture, aneurysm formation, and calcification. ECM proteins control ECM remodeling through feedback signaling to matrix metalloproteinases (MMPs), which are the key players of ECM remodeling in both normal and pathological conditions. The production of MMPs is closely related to the development of an inflammatory response and is subjected to significant changes at different stages of atherosclerosis. Indeed, blood levels of circulating MMPs may be useful for the assessment of the inflammatory activity in atherosclerosis and the prediction of cardiovascular risk. The availability of a wide variety of low-molecular MMP inhibitors that can be conjugated with various labels provides a good perspective for specific targeting of MMPs and implementation of imaging techniques to visualize MMP activity in atherosclerotic plaques and, most interestingly, to monitor responses to antiatheroslerosis therapies. Finally, because of the crucial role of ECM in cardiovascular repair, the regenerative potential of ECM could be successfully used in constructing engineered scaffolds and vessels that mimic properties of the natural ECM and consist of the native ECM components or composite biomaterials. These scaffolds possess a great promise in vascular tissue engineering. PMID:23422022

Chistiakov, Dimitry A; Sobenin, Igor A; Orekhov, Alexander N

114

External imaging of human atherosclerosis  

SciTech Connect

Autologous plasma low-density lipoproteins labeled with /sup 125/I were used as a tracer to identify atherosclerotic lesions in the carotid arteries of the neck. Following intravenous injection of /sup 125/I-LDL, images were made at intervals from 6 to 36 hr with the gamma camera in three patients with known carotid disease and one control subject. The carotid lesions, confirmed by angiography, were imaged successfully in all three patients, whereas no focal LDL accumulation was visible in the carotid arteries of the control subject. The findings suggest that it may be possible to image atherosclerosis externally and thus to follow the course of the disease.

Lees, R.S.; Lees, A.M.; Strauss, H.W.

1983-02-01

115

External imaging of human atherosclerosis  

SciTech Connect

Autologous plasma low-density lipoproteins labeled with I-125 were used as a tracer to identify atherosclerotic lesions in the carotid arteries of the neck. Following intravenous injection of I-125-LDL, images were made at intervals from 6 to 36 hr with the gamma camera in three patients with known carotid disease and one control subject. The carotid lesions, confirmed by angiography, were imaged successfully in all three patients, whereas no focal LDL accumulation was visible in the carotid arteries of the control subject. The findings suggest that it may be possible to image atherosclerosis externally and thus to follow the course of the disease.

Lees, R.S.; Lees, A.M.; Strauss, H.W.

1983-02-01

116

Molecular evidence for arterial repair in atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a chronic inflammatory process and progresses through characteristic morphologic stages. We have shown previously that chronically injecting bone-marrow-derived vascular progenitor cells can effect arterial repair. This repair capacity depends on the age of the injected marrow cells, suggesting a progressive decline in progenitor cell function. We hypothesized that the progression of atherosclerosis coincides with the deteriorating repair capacity

Ravi Karra; Sreekanth Vemullapalli; Chunming Dong; Edward E. Herderick; Xiaohua Song; Kathy Slosek; Joseph R. Nevins; Mike West; Pascal J. Goldschmidt-Clermont; David Seo

2005-01-01

117

An association between atherosclerosis and venous thrombosis  

Microsoft Academic Search

background In about a third of patients with venous thromboembolism, the cause of the disorder is unexplained. In patients with atherosclerosis, activation of both platelets and blood co- agulation and an increase in fibrin turnover are detectable, which may lead to thrombotic complications. Whether atherosclerosis is associated with an increased risk of venous thrombosis is unknown. methods We performed ultrasonography

Paolo Prandoni; Franca Bilora; Antonio Marchiori; Enrico Bernardi; Francesco Petrobelli; Anthonie W. A. Lensing; Martin H. Prins; Antonio Girolami

2003-01-01

118

Cranberry Flavonoids, Atherosclerosis and Cardiovascular Health  

Microsoft Academic Search

Atherosclerosis is the deposition of plaques containing cholesterol and lipids in arterial walls. Atherosclerosis causes cardiovascular disease that lead to heart attacks and stroke. Mortality from these diseases is the leading cause of death in the U.S. Atherogenisis starts with the uptake of oxidized LDL by endothelial macrophages, the accumulation of foam cells in the intima of the artery and

Jess Reed

2002-01-01

119

Maximising antihypertensive effects of angiotensin II receptor blockers with thiazide diuretic combination therapy: focus on irbesartan/hydrochlorothiazide  

PubMed Central

Background Evidence-based guidelines for the management of hypertension are now well established. Studies have shown that more than 60% of patients with hypertension will require two or more drugs to achieve current treatment targets. Discussion Combination therapy is recommended as first-line treatment by the JNC-7 guidelines for patients with a blood pressure > 20 mmHg above the systolic goal or 10 mmHg above the diastolic goal, while the International Society of Hypertension in Blacks recommends combination therapy when BP exceeds targets by > 15/10 mmHg. Current European Society of Hypertension-European Society of Cardiology guidelines also recommend the use of low-dose combination therapy in the first-line setting. Furthermore, JNC-7 recommends that a thiazide-type diuretic should be part of initial first-line combination therapy. Thiazide/diuretic combinations are available for a variety of classes of antihypertensive, including ACE inhibitors, angiotensin receptor blockers (ARBs), beta blockers and centrally acting agents. This article focuses on clinical data investigating the combination of an ARB, irbesartan, with the diuretic, hydrochlorothiazide. Conclusions These data indicate that the ARB/HCTZ combination has greater potency and a similar side effect profile to ARB monotherapy and represents a highly effective approach for attaining goal BP levels using a therapeutic strategy that very effectively lowers BP, is well tolerated and minimises diuretic-induced metabolic effects. Review Criteria The PubMed and other searchable databases were utilized to collate information from original and review articles as well as from selected abstracts relevant to this topic. Message for the Clinic Diuretic-based combination antihypertensive drug therapy is a cornerstone of antihypertensive drug therapy. Most hypertensive patients will require more than one antihypertensive drug to lower blood pressure (BP) below target levels. The combination of diuretics with renin angiotensin system antagonists is highly logical given the significant augmentation of BP response and the minimization of drug-specific side effects (e.g., hypo- and hyperkalemia) when these two drug classes are combined. The combined use of angiotensin receptor blockers and diuretics is better tolerated, but more costly, than generic angiotensin converting enzyme inhibitors and diuretics, mostly because of the absence of cough and much lower incidence of angioedema.

Flack, J M

2007-01-01

120

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

121

RAGE biology, atherosclerosis and diabetes.  

PubMed

Diabetes is characterized by accelerated atherosclerosis with widely distributed vascular lesions. An important mechanism by which hyperglycaemia contributes to vascular injury is through the extensive intracellular and extracellular formation of AGEs (advanced glycation end products). AGEs represent a heterogeneous group of proteins, lipids and nucleic acids, irreversibly cross-linked with reducing sugars. AGEs are implicated in the atherosclerotic process, either directly or via receptor-mediated mechanisms, the most extensively studied receptor being RAGE (receptor for AGEs). The AGE-RAGE interaction alters cellular signalling, promotes gene expression and enhances the release of pro-inflammatory molecules. It elicits the generation of oxidative stress in numerous cell types. The importance of the AGE-RAGE interaction and downstream pathways leading to injurious effects as a result of chronic hyperglycaemia in the development, progression and instability of diabetic atherosclerotic lesions has been amply demonstrated in animal studies. Moreover, the deleterious link of AGEs with diabetic vascular complications has been suggested in many human studies. In the present review, our current understanding of their role as an important mediator of vascular injury through the various stages of atherosclerosis in diabetes will be reviewed and critically assessed. PMID:21457145

Barlovic, Drazenka Pongrac; Soro-Paavonen, Aino; Jandeleit-Dahm, Karin A M

2011-07-01

122

Leukotrienes as Modifiers of Preclinical Atherosclerosis?  

PubMed Central

Preclinical atherosclerosis represents a crucial period associated with several pathophysiological reactions in the vascular wall. Failure to diagnose preclinical atherosclerosis at this stage misses a major opportunity to prevent the long-term consequences of this disease. Surrogate biological and structural vascular markers are available to determine the presence and the extension of preclinical vascular injury in the general population. Examples of surrogate markers are carotid intima media thickness and biomarkers including high-sensitivity C-reactive protein, cell adhesion molecules and matrix metalloproteinases, and leukotrienes. Recently, leukotrienes have been implicated as mediators, biomarkers, and possible therapeutic targets in the context of subclinical atherosclerosis. The aim of this short paper is to focus on the relation between preclinical atherosclerosis and leukotrienes, with particular attention to the recent development on the use of leukotriene modifiers in the treatment of atherosclerosis.

Riccioni, Graziano; Back, Magnus

2012-01-01

123

Biological Imaging of Atherosclerosis: Moving Beyond Anatomy.  

PubMed

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

2013-06-01

124

Atherosclerosis  

MedlinePLUS

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

125

Stimulatory effects of cardiotrophin 1 on atherosclerosis.  

PubMed

Cardiotrophin 1 (CT-1), an interleukin-6 family cytokine, was recently shown to be expressed in the intima of early atherosclerotic lesions in the human carotid artery. CT-1 stimulates proatherogenic molecule expression in human vascular endothelial cells and monocyte migration. However, it has not been reported whether CT-1 accelerates atherosclerosis. This study was performed to examine the stimulatory effects of CT-1 on human macrophage foam cell formation and vascular smooth muscle cell migration and proliferation in vitro, and on the development of atherosclerotic lesions in apolipoprotein E-deficient (ApoE(-/-)) mice in vivo. CT-1 was expressed at high levels in endothelial cells and macrophages in both humans and ApoE(-/-) mice. CT-1 significantly enhanced oxidized low-density lipoprotein-induced foam cell formation associated with increased levels of CD36 and acyl-CoA:cholesterol acyltransferase-1 expression in human monocyte-derived macrophages. CT-1 significantly stimulated the migration, proliferation, and collagen-1 expression in human aortic vascular smooth muscle cells. Four-week infusion of CT-1 into ApoE(-/-) mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte/macrophage infiltration, vascular smooth muscle cell proliferation, and collagen-1 content in the aortic wall. Activation of inflammasome, such as apoptosis-associated speck-like protein containing a caspase recruitment domain, nuclear factor ?B, and cyclooxygenase-2, was observed in exudate peritoneal macrophages from ApoE(-/-) mice infused with CT-1. Infusion of anti-CT-1-neutralizing antibody alone into ApoE(-/-) mice significantly suppressed monocyte/macrophage infiltration in atherosclerotic lesions. These results indicate that CT-1 accelerates the development of atherosclerotic lesions by stimulating the inflammasome, foam cell formation associated with CD36 and acyl-CoA:cholesterol acyltransferase-1 upregulation in macrophages, and migration, proliferation, and collagen-1 production in vascular smooth muscle cells. PMID:24041953

Konii, Hanae; Sato, Kengo; Kikuchi, Sayaka; Okiyama, Hazuki; Watanabe, Rena; Hasegawa, Akinori; Yamamoto, Keigo; Itoh, Fumiko; Hirano, Tsutomu; Watanabe, Takuya

2013-09-16

126

Atherosclerosis in systemic lupus erythematosus.  

PubMed

: 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

2013-09-01

127

Noninvasive Assessment of Preclinical Atherosclerosis  

PubMed Central

Initially considered as a semipermeable barrier separating lumen from vessel wall, the endothelium is now recognised as a complex endocrine organ responsible for a variety of physiological processes vital for vascular homeostasis. These include the regulation of vascular tone, luminal diameter, and blood flow; hemostasis and thrombolysis; platelet and leucocyte vessel-wall interactions; the regulation of vascular permeability; and tissue growth and remodelling. The endothelium modulates arterial stiffness, which precedes overt atherosclerosis and is an independent predictor of cardiovascular events. Unsurprisingly, dysfunction of the endothelium may be considered as an early and potentially reversible step in the process of atherogenesis and numerous methods have been developed to assess endothelial status and large artery stiffness. Methodology includes flow-mediated dilatation of the brachial artery, assessment of coronary flow reserve, carotid intimamedia thickness, pulse wave analysis, pulse wave velocity, and plethysmography. This review outlines the various modalities, indications, and limitations of available methods to assess arterial dysfunction and vascular risk.

Lane, Helen A; Smith, Jamie C; Davies, J Stephen

2006-01-01

128

Aging, Atherosclerosis, and IGF-1  

PubMed Central

Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, and tissue repair. Recent evidence indicates that IGF-1 reduces atherosclerosis burden and improves features of atherosclerotic plaque stability in animal models. Potential mechanisms for this atheroprotective effect include IGF-1–induced reduction in oxidative stress, cell apoptosis, proinflammatory signaling, and endothelial dysfunction. Aging is associated with increased vascular oxidative stress and vascular disease, suggesting that IGF-1 may exert salutary effects on vascular aging processes. In this review, we will provide a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging.

Higashi, Yusuke; Sukhanov, Sergiy; Anwar, Asif; Shai, Shaw-Yung

2012-01-01

129

Small Molecules for the Treatment of Atherosclerosis.  

National Technical Information Service (NTIS)

This invention provides novel small molecules that ameliorate one or more symptoms of atherosclerosis. The small molecules are highly stable and readily administered via an oral route. The small molecules are effective to stimulate the formation and cycli...

A. M. Fogelman G. M. Anantharamaiah M. Navab

2005-01-01

130

Inflammation and immune system interactions in atherosclerosis.  

PubMed

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for 16.7 million deaths each year. The underlying cause of the majority of CVD is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall. Today's picture is far more complex. Atherosclerosis is considered a chronic inflammatory disease that results in the formation of plaques in large and mid-sized arteries. Both cells of the innate and the adaptive immune system play a crucial role in its pathogenesis. By transforming immune cells into pro- and anti-inflammatory chemokine- and cytokine-producing units, and by guiding the interactions between the different immune cells, the immune system decisively influences the propensity of a given plaque to rupture and cause clinical symptoms like myocardial infarction and stroke. In this review, we give an overview on the newest insights in the role of different immune cells and subtypes in atherosclerosis. PMID:23430000

Legein, Bart; Temmerman, Lieve; Biessen, Erik A L; Lutgens, Esther

2013-02-21

131

Atherosclerosis and the internal mammary arteries  

SciTech Connect

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

Singh, R.N.

1983-06-01

132

[Atherosclerosis, oxidative stress and physical activity. Review].  

PubMed

Atherosclerosis and related diseases have emerged as the leading cause of morbidity and mortality in the western world and, therefore, as a problem of public health. Free radicals and reactive oxygen species have been suggested to be part of the pathophysiology of these diseases. It is well known that physical activity plays an important role as a public health measure by reducing the risk of developing atherosclerosis-related cardiovascular events in the general population. It is also known that physical activity increases in some tissues, the reactive oxygen species production. In this review the atherosclerosis-oxidative stress-physical activity relationship is focused on the apparent paradox by which physical activity reduces atherosclerosis and cardiovascular risk in parallel with the activation of an apparently damaging mechanism which is an increased oxidative stress. A hypothesis including the experimental and clinical evidence is presented to explain the aforementioned paradox. PMID:18846779

Calderón, Juan Camilo; Fernández, Ana Zita; María de Jesús, Alina Isabel

2008-09-01

133

Hypertonia and Atherosclerosis under High Mountain Conditions.  

National Technical Information Service (NTIS)

Problems in the development and course of experimental atherosclerosis against a background of renovascular hypertonia and their interaction in long term acclimatization with consideration of the meteorological and heliogeophysical factors operating in th...

M. A. Aliyev R. I. Kulakova

1973-01-01

134

Hydrogen Sulfide and the Pathogenesis of Atherosclerosis.  

PubMed

Abstract Significance: Stigmatized as a toxic environmental pollutant for centuries, hydrogen sulfide (H2S) has gained recognition over the last decade as an important gasotransmitter that functions in physiological and pathophysiological conditions, such as atherosclerosis. Recent Advances: Atherosclerosis is a common disease that stems from the buildup of fatty/cholesterol plaques on the endothelial cells of arteries. The deposits mitigate thickening and stiffening of arterial tissue, which contributes to concomitant systemic or localized vascular disorders. Recently, it has been recognized that H2S plays an anti-atherosclerotic role, and its deficiency leads to early development and progression of atherosclerosis. This review article presents multiple lines of evidence for the protective effects of H2S against the development of atherosclerosis. Also highlighted are the characterization of altered metabolism of H2S in the development of atherosclerosis, underlying molecular and cellular mechanisms, and potential therapeutic intervention based on H2S supplementation for atherosclerosis management. Critical Issues: Although a protective role of H2S against atherosclerosis has emerged, controversy remains regarding the mechanisms underlying H2S-induced endothelial cell proliferation and angiogenesis as well as its anti-inflammatory properties. The therapeutic value of H2S to this pathophysiological condition has not been tested clinically but, nonetheless, it shows tremendous promise. Future Directions: The efficiency and safety profile of H2S-based therapeutic approaches should be refined, and the mechanisms by which H2S exerts its beneficial effects should be elucidated to develop more specific and potent therapeutic strategies to treat atherosclerosis. Whether the therapeutic effects of H2S in animal studies are transferable to clinical studies merits future investigation. Antioxid. Redox Signal. 00, 000-000. PMID:23582095

Mani, Sarathi; Untereiner, Ashley; Wu, Lingyun; Wang, Rui

2013-05-21

135

Homocysteine: Role and implications in atherosclerosis  

Microsoft Academic Search

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

Sasidhar Guthikonda; William G. Haynes

2006-01-01

136

Venous thromboembolism in patients with symptomatic atherosclerosis.  

PubMed

Patients with atherosclerosis have an increased risk of venous thromboembolism (VTE). We studied patients in the population-based Worcester VTE Study of 1,822 consecutive patients with validated VTE to compare clinical characteristics, prophylaxis, treatment, and outcomes of VTE in patients with and without symptomatic atherosclerotic cardiovascular disease, defined as history of ischaemic heart disease, history of positive cardiac catheterisation, percutaneous coronary intervention, or coronary artery bypass graft surgery, or history of peripheral artery disease. Of the 1,818 patients with VTE, 473 (26%) had a history of symptomatic atherosclerosis. Patients with atherosclerosis were significantly older (mean age 71.9 years vs. 61.6 years) and were more likely to have immobility (57.2% vs. 46.7%), prior heart failure (36.9% vs. 10.7%), chronic lung disease (26.4% vs. 15.5%), cerebrovascular disease (18.1% vs. 9.8%), and chronic kidney disease (4.9% vs. 1.9%) (all p<0.001) compared with non-atherosclerosis patients. Thromboprophylaxis was omitted in more than one-third of atherosclerosis patients who had been hospitalised for non-VTE-related illness or had undergone major surgery within the three months prior to VTE. Patients with atherosclerosis were significantly more likely to suffer in-hospital major bleeding (7.6% vs. 3.8%, p=0.0008). In conclusion, patients with atherosclerosis and VTE are more likely to suffer a complicated hospital course. Despite a high frequency of comorbid conditions contributing to the risk of VTE, we observed a low rate of thromboprophylaxis in patients with symptomatic atherosclerosis. PMID:22012325

Piazza, Gregory; Goldhaber, Samuel Z; Lessard, Darleen M; Goldberg, Robert J; Emery, Catherine; Spencer, Frederick A

2011-10-20

137

Functions of cyclophilin A in atherosclerosis  

PubMed Central

Cyclophilin A (CypA) is a ubiquitously distributed protein present both in intracellular and extracellular spaces. In atherosclerosis, various cells, including endothelial cells, monocytes, vascular smooth muscle cells and platelets, secrete CypA in response to excessive levels of reactive oxygen species. Atherosclerosis, a complicated disease, is the result of the interplay of different risk factors. Researchers have found that CypA links many risk factors, including hyperlipidemia, hypertension and diabetes, to atherosclerosis that develop into a vicious cycle. Furthermore, most studies have shown that secreted CypA participates in the developmental process of atherosclerosis via many important intracellular mechanisms. CypA can cause injury to and apoptosis of endothelial cells, leading to dysfunction of the endothelium. CypA may also induce the activation and migration of leukocytes, producing proinflammatory cytokines that promote inflammation in blood vessels. In addition, CypA can promote the proliferation of monocytes/macrophages and vascular smooth muscle cells, leading to the formation of foam cells and the remodelling of the vascular wall. Studies investigating the roles of CypA in atherosclerosis may provide new direction for preventive and interventional treatment strategies in atherosclerosis.

Tian-tian, Zhang; Jun-feng, Zhang; Heng, Ge

2013-01-01

138

Functions of cyclophilin A in atherosclerosis.  

PubMed

Cyclophilin A (CypA) is a ubiquitously distributed protein present both in intracellular and extracellular spaces. In atherosclerosis, various cells, including endothelial cells, monocytes, vascular smooth muscle cells and platelets, secrete CypA in response to excessive levels of reactive oxygen species. Atherosclerosis, a complicated disease, is the result of the interplay of different risk factors. Researchers have found that CypA links many risk factors, including hyperlipidemia, hypertension and diabetes, to atherosclerosis that develop into a vicious cycle. Furthermore, most studies have shown that secreted CypA participates in the developmental process of atherosclerosis via many important intracellular mechanisms. CypA can cause injury to and apoptosis of endothelial cells, leading to dysfunction of the endothelium. CypA may also induce the activation and migration of leukocytes, producing proinflammatory cytokines that promote inflammation in blood vessels. In addition, CypA can promote the proliferation of monocytes/macrophages and vascular smooth muscle cells, leading to the formation of foam cells and the remodelling of the vascular wall. Studies investigating the roles of CypA in atherosclerosis may provide new direction for preventive and interventional treatment strategies in atherosclerosis. PMID:23940449

Tian-Tian, Zhang; Jun-Feng, Zhang; Heng, Ge

2013-01-01

139

Osteoprotegerin, vascular calcification and atherosclerosis  

PubMed Central

The association of bone pathologies with atherosclerosis has stimulated the search for common mediators linking the skeletal and the vascular system. Since its initial discovery as a key regulator in bone metabolism, osteoprotegerin (OPG) has become the subject of intense interest for its role in vascular disease and calcification. Studies in vitro and in animal models suggest that OPG inhibits vascular calcification. Paradoxically however, clinical studies suggest that serum OPG levels increase in association with vascular calcification, coronary artery disease, stroke and future cardiovascular events. This has led to extensive debate on the potential of OPG as a biomarker of vascular disease. However the exact significance and mechanisms by which this bone-regulatory protein influences cardiovascular pathophysiology is still unclear. The need for a more complete picture is being addressed in increasing valuable research indicating OPG as not only a marker but also a mediator of vascular pathology modulating osteogenic, inflammatory and apoptotic responses. By integrating the results of recent experimental research, animal models and clinical studies, this review summarises the present understanding of the role of OPG in vascular disease and calcification.

Van Campenhout, Ann; Golledge, Jonathan

2009-01-01

140

Nitric oxide function in atherosclerosis  

PubMed Central

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

Matthys, K. E.

1997-01-01

141

Superoxide and Peroxynitrite in Atherosclerosis  

NASA Astrophysics Data System (ADS)

The role of reactive oxygen species in the vascular pathology associated with atherosclerosis was examined by testing the hypothesis that impaired vascular reactivity results from the reaction of nitric oxide (^.NO) with superoxide (O^-_2), yielding the oxidant peroxynitrite (ONOO^-). Contractility studies were performed on femoral arteries from rabbits fed a cholesterol-supplemented diet. Cholesterol feeding shifted the EC50 for acetylcholine (ACh)-induced relaxation and impaired the maximal response to ACh. We used pH-sensitive liposomes to deliver CuZn superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) to critical sites of ^.NO reaction with O^-_2. Intravenously injected liposomes (3000 units of SOD per ml) augmented ACh-induced relaxation in the cholesterol-fed group to a greater extent than in controls. Quantitative immunocytochemistry demonstrated enhanced distribution of SOD in both endothelial and vascular smooth muscle cells as well as in the extracellular matrix. SOD activity in vessel homogenates of liposome-treated rabbits was also increased. Incubation of ? very low density lipoprotein with ONOO^- resulted in the rapid formation of conjugated dienes and thiobarbituric acid-reactive substances. Our results suggest that the reaction of O^-_2 with ^.NO is involved in the development of atherosclerotic disease by yielding a potent mediator of lipoprotein oxidation, as well as by limiting ^.NO stimulation of vascular smooth muscle guanylate cyclase activity.

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

1994-02-01

142

The CD1d-Natural Killer T Cell Axis in Atherosclerosis.  

PubMed

A key role for 'lipid-sensing' CD1-restricted natural killer T (NKT) cells in the pathogenesis of atherosclerosis has been suggested. However, the biology of NKT cells remains poorly characterized, as in different experimental settings their activation was reported to both stimulate and suppress innate and adaptive immune responses. Most of the data from experimental models suggest that NKT cells are proatherogenic; however, it is debated whether the increase in atherosclerosis observed following NKT cell stimulation is a consequence of the inability to induce functional NKT cells rather than the proatherogenic nature of NKT cells. CD1d-expressing antigen-presenting cells and NKT cells were detected in mouse and human atherosclerotic lesions. Furthermore, several lysophospholipids and glycosphingolipids, known to accumulate in atherosclerotic plaques, are antigenic for human NKT cell clones. Lipid transfer proteins, such as apolipoprotein E and microsomal triglyceride transfer protein, are central to NKT cell responses. All these data suggest a profound relation between lipid metabolism, CD1d-NKT cell axis activation and atherosclerosis. In this review, we summarize the advances and gaps in our knowledge of NKT cell biology in the context of atherosclerosis as well as the possibility of influencing NKT cell polarization toward an atheroprotective phenotype. PMID:23774666

Bondarenko, Sergey; Catapano, Alberico Luigi; Norata, Giuseppe Danilo

2013-06-13

143

Paeonol attenuates high-fat-diet-induced atherosclerosis in rabbits by anti-inflammatory activity.  

PubMed

Cortex Moutan (Paeonia suffruticosa Andrews, Ranunculaceae) has several uses in traditional medicine, such as analgesic, antipyretic, and anti-inflammatory applications and use in the prevention of thromboembolic diseases. Paeonol, a main active component in Cortex Moutan, possesses various pharmacological activities, particularly an anti-atherosclerosis effect. However, so far there have been no reports evaluating the anti-inflammatory action of paeonol in atherosclerosis therapy. The purpose of this study was to investigate the association of the therapeutic effect of paeonol on atherosclerotic rabbits with its anti-inflammatory action. The atherosclerotic model was developed in 24 rabbits fed a high-fat diet for 12 weeks. Twelve rabbits on the high-fat diet then were administered with paeonol (p.o) for a subsequent 6 weeks at the doses of 75 mg/kg and 150 mg/kg. Histological analysis showed significant improvement in atherosclerosis plaque in the paeonol groups. Moreover, the blood levels of TNF- alpha, IL-1 beta, and CRP and the translocation of NF- kappaB to the nucleus were significantly suppressed in paeonol groups, as was the inhibition of lipid peroxidation. In conclusion, these findings suggest that the anti-inflammatory action of paeonol may contribute to its anti-atherosclerosis effect. PMID:19003727

Li, Houkai; Dai, Min; Jia, Wei

2008-11-10

144

Metabonomics-based omics study and atherosclerosis  

PubMed Central

Atherosclerosis results from dyslipidemia and systemic inflammation, associated with the strong metabolism and interaction between diet and disease. Strategies based on the global profiling of metabolism would be important to define the mechanisms involved in pathological alterations. Metabonomics is the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification. Metabonomics has been used in combination with proteomics and transcriptomics as the part of a systems biology description to understand the genome interaction with the development of atherosclerosis. The present review describes the application of metabonomics to explore the potential role of metabolic disturbances and inflammation in the initiation and development of atherosclerosis. Metabonomics-based omics study offers a new potential for biomarker discovery by disentangling the impacts of diet, environment and lifestyle.

2011-01-01

145

Molecular evidence for arterial repair in atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory process and progresses through characteristic morphologic stages. We have shown previously that chronically injecting bone-marrow-derived vascular progenitor cells can effect arterial repair. This repair capacity depends on the age of the injected marrow cells, suggesting a progressive decline in progenitor cell function. We hypothesized that the progression of atherosclerosis coincides with the deteriorating repair capacity of the bone marrow. Here, we ascribe patterns of gene expression that accurately and reproducibly identify specific disease states in murine atherosclerosis. We then use these expression patterns to determine the point in the disease process at which the repair of arteries by competent bone marrow cells ceases to be efficient. We show that the loss of the molecular signature for competent repair is concurrent with the initiation of atherosclerotic lesions. This work provides a previously unreported comprehensive molecular data set using broad-based analysis that links the loss of successful repair with the progression of a chronic illness.

Karra, Ravi; Vemullapalli, Sreekanth; Dong, Chunming; Herderick, Edward E.; Song, Xiaohua; Slosek, Kathy; Nevins, Joseph R.; West, Mike; Goldschmidt-Clermont, Pascal J.; Seo, David

2005-01-01

146

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

PubMed Central

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

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

2011-01-01

147

FURTHER STUDIES IN EXPERIMENTAL ATHEROSCLEROSIS  

PubMed Central

Cholesterol dissolved in sesame oil and injected regularly for a period of from 7 to 8 months into the jugular vein of four young dogs has caused in each animal larger and smaller nodules protruding to some degree into the lumen of the pulmonary artery and also here and there some diffuse thickenings, the whole closely resembling human arteriosclerosis. These changes commence at the origin of the pulmonary artery immediately behind the semilunar valves. They seem a little more pronounced in those dogs that had the aorta tied. Microscopically the lesions are seen to be primary in the media. They consist of a more or less violent disorganization of the elastic elements and displacement of the muscular tissue. As a consequence wide gaps, apparently filled with plasma, are formed in the media. The entire process is localized principally in the inner third of the media. There is no evidence of fatty degeneration either in the elastic elements or the muscle. Typical sclerotic hyperplasia of the intima is found over some of the prominent median nodulations while over others the intima is normal. Hyperplastic sclerosis of the intima is also found in places where the media is intact or only slightly damaged. Some of the larger branches of the pulmonary artery well within the lung tissue are somewhat dilated and show extensive hyperplasia of the intima over almost normal media. Peculiar small nodules are seen in the media of the two main branches of the pulmonary artery which are found to consist of frank hyperplasia of the elastic and muscular elements arranged in more or less regular concentric circles. The capillaries and smaller and smallest arteries within the lungs are not affected. Cholesterol in phagocytes and in droplets between the tissue elements is present in very small quantities and does not take any active part in the process. The entire process represents in all probability an early stage of arteriosclerosis, a result of purely mechanical stress brought about by the very extensive but more or less intermittent blocking of the pulmonary circulation by the oil. The musculature of the artery appears to be the main force applied to overcome the resistance in the circulation. In no case has hypertrophy of the right heart been found. The lesions in the pulmonary arteries of the dogs produced experimentally are closely analogous to atherosclerosis of the human pulmonary artery.

Adler, I.

1917-01-01

148

Coronary atherosclerosis: where are we now?  

PubMed

An attempt is made to present and summarize recent results in atherosclerosis research which may aid to a better understanding of atherogenesis, progression of atherosclerotic lesions and occurrence of myocardial ischemia. Based on selected data from the available literature and the authors' experience, the review focuses the attention on: the atherogenic role of hemodynamic stresses; the onset and fate of early coronary atherosclerotic lesions; the development of lesions of possible clinical significance; the concept of "critical stenosis"; the view that atherosclerosis is a hyperplastic and/or neoplastic disease. PMID:3041551

Velican, C; Velican, D

149

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

PubMed Central

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

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

2009-01-01

150

Identification and characterization of degradation products of irbesartan using LC-MS/TOF, MS(n), on-line H/D exchange and LC-NMR.  

PubMed

Irbesartan was subjected to hydrolytic, oxidative, photolytic and thermal stress, according to ICH guideline Q1A (R2). The drug showed degradation only in acidic, basic and photoacidic conditions, while it was stable to other stress conditions. A total of three degradation products were formed, which were separated on a C-8 column employing a gradient HPLC method. Initially, a complete mass fragmentation pathway of the drug was established with the help of MS/TOF, MS(n) and H/D exchange studies. Subsequently, the degradation products were subjected to LC-MS/TOF and on-line H/D exchange mass studies to obtain their accurate mass, fragment pattern and number of labile hydrogens. The MS results helped to assign tentative structures to degradation products, which were verified through (1)H and 2D COSY LC-NMR experiments. The products were identified as (2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methanamine, 1-(1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methylamino)pentylideneamino)cyclopentane carboxylic acid and 2-butyl-3-(tetrazolo[1,5-f]phenanthridin-6-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one. The structures were justified by mechanisms of their formation. PMID:20018473

Shah, Ravi P; Sahu, Archana; Singh, Saranjit

2009-11-13

151

Fire Suppression  

Microsoft Academic Search

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

C. Presser; J. C. Yang

152

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

PubMed

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

Wang, Li; Li, Haiying; Zhang, Jinfeng; Lu, Wei; Zhao, Jing; Su, Le; Zhao, Baoxiang; Zhang, Yun; Zhang, Shangli; Miao, Junying

2013-08-19

153

Collateral circulation in symptomatic intracranial atherosclerosis  

Microsoft Academic Search

Collateral circulation in intracranial atherosclerosis has never been systematically characterized. We investigated collaterals in a multicenter trial of symptomatic intracranial atherosclerotic disease. Baseline angiography was reviewed for information on collaterals in stenoses of the internal carotid, middle cerebral, vertebral, and basilar arteries. A battery of angiographic scales was utilized to evaluate lesion site, arterial patency, antegrade flow, downstream territorial perfusion,

David S Liebeskind; George A Cotsonis; Jeffrey L Saver; Michael J Lynn; Harry J Cloft; Marc I Chimowitz

2011-01-01

154

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

155

Inhibition of Atherosclerosis by Diindolylmethane Analogs.  

National Technical Information Service (NTIS)

Diindolylmethane analogs such as 1,1-bis(3'-indolyl) -1-(p-substituted phenyl)methanes can be used to treat atherosclerosis and other vascular disease states. The analogs have been shown to display antiinflammatory effects in endothelial cells, suggesting...

E. T. H. Yeh I. J. Samudio P. Calabro S. H. Safe

2005-01-01

156

Is atherosclerosis an immunologically mediated disease?  

Microsoft Academic Search

In contrast to general beliefs, recent data from different laboratories have provided evidence that the first stages of atherosclerosis are of an inflammatory nature. Here, Georg Wick and colleagues suggest that an autoimmune reaction against heat shock protein 60 (Hsp60), expressed by endothelial cells in areas that are subject to increased haemodynamic stress, is the initiating event in atherogenesis. Humoral

Georg Wick; Georg Schett; Albert Amberger; Roman Kleindienst; Qingbo Xu

1995-01-01

157

Atherosclerosis: a nutritional disease of childhood  

Microsoft Academic Search

The development of coronary atherosclerosis begins in childhood. A clear relation between diet and cardiovascular disease risk has been demonstrated. Findings from the Bogalusa Heart Study indicate that most children still exceed national recommendations for intake of total and saturated fat. In addition, children’s mean total energy intake is greater than energy expenditure, contributing to the high prevalence of obesity

Gerald S Berenson; Sathanur R Srinivasan; Theresa A Nicklas

1998-01-01

158

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.

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

2012-01-01

159

Transgenic rabbits as models for atherosclerosis research  

Microsoft Academic Search

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

Margaret E. Brousseau; Jeffrey M. Hoeg

160

Insulin resistance and atherosclerosis in diabetes mellitus.  

PubMed

The aim of this study was to test our hypothesis that insulin resistance determines systemic atherosclerosis in type 2 diabetic patients. The design of the study was cross-sectional and included 28 type 2 patients with 48 type 1 patients as controls. The total daily insulin dose required to maintain glycosylated hemoglobin, HbA(1c), at 6.0% for 1 year was used as a measure of long-term insulin resistance. Systemic atherosclerosis was estimated by the toe systolic blood pressure index (TSPI). The results showed that total daily insulin dose was closely and independently associated with TSPI (r =.4652, partial P =.0064) in type 2 diabetic patients with secondary failure, even when adjusted for serum C-peptide (r =.4443, partial P =.00123). The association was absent in type 1 patients. Established risk factors were not associated with TSPI, but the products between individual risk factors and insulin dose were closely associated with TSPI. In conclusion, the daily insulin dose is associated with peripheral atherosclerosis in type 2 diabetic patients with high insulin resistance, but not in type 1 diabetes. The effect is additive to a lesser, underlying effect of established risk factors on atherosclerosis. Longstanding insulin resistance, as estimated by the daily insulin dose, is a determinant of atherogenesis. PMID:12145764

Wollesen, Flemming; Berglund, Lars; Berne, Christian

2002-08-01

161

Pathogenesis of atherosclerosis: A multifactorial process  

PubMed Central

Atherosclerosis is a leading cause of mortality and morbidity in the western world. It has been recognized for over a century, and the understanding of its pathogenesis has undergone many changes. Pathophysiological studies have unravelled the interactions of molecular and cellular elements involved in atherogenesis. The focus has shifted to the novel risk factors as well as characteristics and stability of atherosclerotic plaque; the genetic predisposition has further broadened the pathogenetic mechanisms. This review focuses on the molecular mechanisms involved in the evolution of the atherosclerotic plaque that may pave the way for selecting optimal therapies and preventing plaque complications. Atherosclerosis is no longer a disease attributed mainly to the high lipid content of the body. New insight into the disease pathology has shown it to be a disease of much greater ramifications. Endothelial damage and reactive oxygen species (and other free radicals) have predominantly emerged as factors in virtually all pathways leading to the development of atherosclerosis due to hyperlipidemia, diabetes, hypertension or smoking. Novel risk factors such as hyperhomocysteinemia, infections and systemic lupus erythematosus have emerged. Atherosclerosis has come to be regarded as a chronic inflammatory disease with an autoimmune component. The genetic basis of the disease assumes significance as candidate genes are identified and gene therapy becomes a promising new addition to the existing, less substantial conventional therapies.

Singh, Raja B; Mengi, Sushma A; Xu, Yan-Jun; Arneja, Amarjit S; Dhalla, Naranjan S

2002-01-01

162

VEGF polymorphisms and severity of atherosclerosis  

PubMed Central

Introduction: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, and neovascularisation has been shown to be important in atherosclerotic plaque development. There is some disagreement as to whether VEGF acts as a pro-atherosclerotic or anti-atherosclerotic factor. In the present study we have sought to clarify this by determining genotypes and haplotypes for three reportedly functional VEGF SNPs in a large series of well documented coronary atherosclerosis patients. Methods: VEGF –2578, –1154, and –634 single nucleotide polymorphisms were genotyped in 984 subjects from the Southampton Atherosclerosis Study, using the 5' nuclease assay for allelic discrimination (TaqMan). Results: VEGF –2578 genotypes showed a significantly different distribution in patients without myocardial infarction when stratified according to number of diseased arteries. VEGF –2578 was also associated with mean number of stenotic segments in the same patient group. The AA genotype was a risk factor and CC was protective. These associations were significant before and after adjustment for classic risk factors, and were reflected in associations between VEGF haplotypes and the number of diseased arteries and stenotic segments. As VEGF –2578 CC has been provisionally shown to be associated with higher VEGF expression than the AA genotype, these results are consistent with a protective effect for VEGF in atherosclerosis development. Some changes in VEGF –1154 genotype frequencies were also detected, but no significant associations were detected for any one particular genotype. Conclusions: This study provides preliminary evidence that VEGF polymorphism is associated with development of atherosclerosis, possibly via regulation of VEGF expression, supporting a protective effect for VEGF in atherosclerosis. These results require replication in an independent study group, combined with study of additional candidate polymorphisms in the VEGF gene.

Howell, W; Ali, S; Rose-Zerilli, M; Ye, S

2005-01-01

163

Intracranial Atherosclerosis: Incidence, Diagnosis and Treatment  

PubMed Central

Intracranial atherosclerosis is considered a cause of approximately 8% of all strokes in the western society. However, its frequency is much higher in Asian countries. In our hospital-based study, among the patients who had angiographic abnormalities, the frequency of intracranial atherosclerosis was approximately 70% far exceeding that of extratracranial atherosclerosis. Symptomatic atherosclerotic diseases were most often found in the middle cerebral artery. Generally, it has been shown that obesity and hyperlipidemia are related to extracranial diseases while advance hypertension is associated with intracranial diseases. However, these results have not always been replicated, and certain genetic factors may be related with the ethnic differences in the location of atherosclerosis. Recent studies using diffusion weighted MRI showed that the main mechanisms of stroke in patients with intracranial atherosclerosis are the branch occlusion, artery to artery embolism and both. The intracranial stenosis, especially symptomatic one, is not a static condition and may progress or regress in a relatively short period of time. Progressive stenosis of intracranial arteries is clearly related to the development of ischemic events. The annual risk of stroke relevant to the stenosed intracranial vessel is approximately 8%. In retrospective studies including ASID, anticoagulation was found to be superior to aspirin in reducing the stroke events. However, a recent prospective study failed to confirm the superiority of anticoagulation over aspirin in patients with intracranial stenosis. Moreover, anticoagulation resulted in excessive central nervous system bleeding as compared to aspirin. Because aspirin alone seems to be insufficient in the prevention of progression of intracranial stenosis, a combination of antiplatelets has been tried. Recently, we found that a combination of aspirin + cilostazol was superior to aspirin monotherapy in the prevention of progression of symptomatic intracranial stenosis. However, further studies are required to find out the best combination of antiplatelets for symptomatic intracranial stenosis. The effect of other atheroma stabilizers such as statins should also be properly evaluated. Angioplasty/stent is another important option for the relatively severe intracranial stenosis. According to previous studies, immediate success rate has reached up to 90%. If patients are carefully selected, and procedures done by experienced hand, angioplasty/stent can be of benefit especially in relatively young patients with proximal, short-segment, severe symptomatic stenosis. However, this procedure is not without complications or long-term re-stenosis. Further studies are required to elucidate the best therapeutic strategy in patients with intracranial atherosclerosis.

Kang, Dong-Wha; Kwon, Sun U.

2005-01-01

164

Endothelial MicroRNAs and Atherosclerosis.  

PubMed

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

2013-12-01

165

Connecting the Lines between Hypogonadism and Atherosclerosis  

PubMed Central

Epidemiological studies show that atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality worldwide and point to gender differences with ageing males being at highest risk. Atherosclerosis is a complex process that has several risk factors and mediators. Hypogonadism is a commonly undiagnosed disease that has been associated with many of the events, and risk factors leading to atherosclerosis. The mechanistic relations between testosterone levels, atherosclerotic events, and risk factors are poorly understood in many instances, but the links are clear. In this paper, we summarize the research journey that explains the link between hypogonadism, each of the atherosclerotic events, and risk factors. We look into the different areas from which lessons could be learned, including epidemiological studies, animal and laboratory experiments, studies on androgen deprivation therapy patients, and studies on testosterone-treated patients. We finish by providing recommendations for the clinician and needs for future research.

Fahed, Akl C.; Gholmieh, Joanna M.; Azar, Sami T.

2012-01-01

166

Leukotriene signaling in atherosclerosis and ischemia  

PubMed Central

Introduction The inflammatory process of atherosclerosis is associated with several pathophysiological reactions within the vascular wall. The arachidonic acid released by phospholipase A2 serves as substrate for the production of a group of lipid mediators known as the leukotrienes, which induce pro-inflammatory signaling through activation of specific BLT and CysLT receptors. Discussion Leukotriene signaling has been implicated in early lipid retention and foam cell accumulation, as well as in the development of intimal hyperplasia and advanced atherosclerotic lesions. Furthermore, the association of leukotrienes with degradation of extracellular matrix has suggested a role in atherosclerotic plaque rupture. Finally, studies of either myocardial or cerebral ischemia and reperfusion indicate that leukotriene signaling in addition may be involved in the development of ischemic injury. Conclusion Both leukotriene synthesis inhibitors and leukotriene receptor antagonists have been suggested to induce beneficial effects at different stages of the atherosclerosis process.

Back, Magnus

2009-01-01

167

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

168

Lipidomics: A Tool for Studies of Atherosclerosis  

Microsoft Academic Search

Lipids, abundant constituents of both the vascular plaque and lipoproteins, play a pivotal role in atherosclerosis. Mass spectrometry-based\\u000a analysis of lipids, called lipidomics, presents a number of opportunities not only for understanding the cellular processes\\u000a in health and disease but also in enabling personalized medicine. Lipidomics in its most advanced form is able to quantify\\u000a hundreds of different molecular lipid

Kim Ekroos; Minna Jänis; Kirill Tarasov; Reini Hurme; Reijo Laaksonen

2010-01-01

169

Vaccination against atherosclerosis? Induction of atheroprotective immunity  

Microsoft Academic Search

Atherosclerosis involves the formation of inflammatory arterial lesions and is one of the most common causes of death globally.\\u000a It has been evident for more than 20 years that adaptive immunity regulates the magnitude of the atherogenic proinflammatory\\u000a response. T cells may also influence the stability of the atherosclerotic lesion and thus the propensity for thrombus formation\\u000a and the clinical

Göran K. Hansson; Jan Nilsson

2009-01-01

170

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

171

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

172

Doinseunggitang Ameliorates Endothelial Dysfunction in Diabetic Atherosclerosis  

PubMed Central

Atherosclerosis, a chronic and progressive disease characterized by vascular inflammation, is a leading cause of death in diabetes patients. Doinseunggitang (DYSGT), traditional prescription, has been used for promoting blood circulation to remove blood stasis. The aim of this study was to investigate the beneficial effects of DYSGT on endothelial dysfunction in diabetic atherosclerosis animal model. Apolipoprotein E knockout (ApoE KO) mice fed on a Western diet were treated with DYSGT (200?mg/kg/day). DYSGT significantly lowered blood glucose level and glucose tolerance as well as systolic blood pressure. Metabolic parameter showed that DYSGT markedly decreased triglyceride and LDL-cholesterol levels. In the thoracic aorta, the impairment of vasorelaxation response to acetylcholine and atherosclerotic lesion was attenuated by DYSGT. Furthermore, DYSGT restored the reduction of endothelial nitric oxide synthase (eNOS) expression, leading to the inhibition of intracellular adhesion molecule-1 (ICAM-1) and endothelin-1 (ET-1) expression. In conclusion, DYSGT improved the development of diabetic atherosclerosis via attenuation of the endothelial dysfunction, possibly by inhibiting ET-1, cell adhesion molecules, and lesion formation. Therefore, these results suggest that Korean traditional prescription Doinseunggitang may be useful in the treatment and prevention of diabetic vascular complications.

Yoon, Jung Joo; Lee, Yun Jung; Park, Ok Ju; Lee, So Min; Lee, Yong Pyo; Cho, Nam Geun; Kang, Dae Gill; Lee, Ho Sub

2013-01-01

173

Advanced glycation: a novel outlook on atherosclerosis.  

PubMed

Atherosclerosis is a major global cause of morbidity and mortality, and diabetes patients are at increased risk of coronary heart disease development. Advanced glycation of proteins occurs in the body due to raised concentrations of reducing sugars and reactive oxygen species, and is a causal factor behind complications of diabetes. Glycated proteins, through alteration of protein structure and function, and from ligation with their receptors, lead to widespread vascular damage. The alpha-oxoaldehyde, methylglyoxal (MG) is the most reactive glycation precursor, and is increased in the blood of diabetes patients. There is debate about the triggering events leading to atherosclerosis, but the inflammatory action of glycated proteins, including those with MG adducts, through their receptor, RAGE, is a major candidate for initiating plaque formation. In addition glycation may cause cross-links on proteins of the extracellular matrix, stiffening arteries and 'trapping' other macromolecules. MG is also likely to form adducts on many other proteins, enzymes, lipids, DNA or RNA, changing their structure, and may disrupt enzyme activity, hormone regulation and immune function. In the latter context, MG disrupts function of the potent antigen presenting cells, dendritic cells. This effect may be a double edged sword: Poor control of infections may contribute to persistent inflammation, whilst inhibition of immune activation by dendritic cells may inhibit plaque progression. This review aims to present these ideas as a novel slant on the role of the glycation process in atherosclerosis. PMID:18220806

Price, C L; Knight, S C

2007-01-01

174

The role of transferrin in atherosclerosis.  

PubMed

Transferrin is a plasma protein with the primary role of transporting iron through the body and delivering it to the cells that utilize it. Because free ionic iron is very toxic by creating free radicals, the importance of transferrin lies in its antioxidant properties. Atherosclerosis, a pathological process affecting arterial walls, is a chronic inflammatory response in which oxidative stress caused by free radicals is a key factor in its pathogenesis. We postulate therefore that the plasma protein transferrin acts protectively in these events, by holding iron in containment and reducing oxidative stress. Furthermore, it is possible that a disturbance in transferrin function and homeostasis is a direct factor triggering and exacerbating atherosclerosis. Decreased transferrin levels, increased transferrin saturation, defective transferrin binding of iron, or other disorders may lead to increased oxidative stress and lipid peroxidation involved in the pathology of atherosclerosis. Some oxidative stress-related diseases have been linked to such systemic transferrin abnormalities, and we hypothesize that similar disruptions could account for an unfavorable microenviroment in the evolvement of atherosclerotic plaques. If confirmed, this proposed mechanism would significantly improve our understanding of the disease. PMID:17959319

Kibel, Aleksandar; Belovari, Tatjana; Drenjancevi?-Peri?, Ines

2007-10-23

175

Periodontal pathogen accelerates lipid peroxidation and atherosclerosis.  

PubMed

Recent studies have shown an association between periodontal disease and cardiovascular disease. We previously reported that intravenous challenge with Aggregatibacter actinomycetemcomitans (Aa) accelerated atherosclerosis in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice. In this study, we investigated whether live cells were required for atherosclerosis induction or whether lipopolysaccharide (LPS) alone was sufficient to increase atherosclerotic damage. Mice were injected intravenously with live Aa HK1651, heat-killed (H.K.) Aa, or Aa LPS 3 times a week for 3 weeks and were sacrificed at 15 weeks of age. The areas of the aortic sinus that were covered with atherosclerotic plaques were significantly larger in mice treated with live Aa, H.K. Aa, or Aa LPS compared with vehicle-challenged mice. The order of the extent of atherosclerosis was live Aa > H.K. Aa > Aa LPS > sham. Toll and nucleotide oligomerization domain (NOD)-like receptor mRNA expression significantly increased in the live Aa, H.K. Aa, and Aa LPS treatment groups. Aa challenge markedly promoted the oxidation of LDL through oxidative stress involving NADPH oxidase- and myeloperoxidase-derived reactive oxygen species. These results suggested that Aa promoted innate immune signaling and low-density lipoprotein (LDL) oxidation and may facilitate atheroma development. PMID:23355524

Jia, R; Kurita-Ochiai, T; Oguchi, S; Yamamoto, M

2013-01-25

176

Plasmacytoid dendritic cells protect against atherosclerosis by tuning T cell proliferation and activity  

PubMed Central

Rationale Unlike conventional dendritic cells (cDC), plasmacytoid DCs (pDC) are poor in antigen presentation and critical for type I interferon response. While proposed to be present in human atherosclerotic lesions, their role in atherosclerosis remains elusive. Objective To investigate the role of pDC in atherosclerosis. Methods and Results We show that pDC are scarcely present in human atherosclerotic lesions, and almost absent in mouse plaques. Surprisingly, pDC depletion by 120G8 mAb administration was seen to promote plaque T cell accumulation and exacerbate lesion development and progression in LDLr?/? mice. PDC depletion was accompanied by increased CD4+ T cell proliferation, IFN-? expression by splenic T cells and plasma IFN-? levels. Lymphoid tissue pDC from atherosclerotic mice showed increased indoleamine 2,3-dioxygenase (IDO) expression and IDO blockage abrogated the pDC suppressive effect on T cell proliferation. Conclusion Our data reveal a protective role for pDC in atherosclerosis, possibly by dampening T cell proliferation and activity in peripheral lymphoid tissue, rendering pDC an interesting target for future therapeutic interventions.

Daissormont, Isabelle T.M.N.; Christ, Anette; Temmerman, Lieve; Millares, Stefan Sampedro; Seijkens, Tom; Rousch, Mat; Poggi, Marjorie; Boon, Louis; van der Loos, Chris; Daemen, Mat; Lutgens, Esther; Halvorsen, Bente; Aukrust, Pal; Janssen, Edith; Biessen, Erik A.L.

2011-01-01

177

Dietary Management for Coronary Atherosclerosis Prevention and Treatment  

Microsoft Academic Search

\\u000a What are the main complications of coronary atherosclerosis? What is the manner in which people succumb to cardiac death?\\u000a The most effective way of improving survival in patients with coronary atherosclerosis is to focus prevention on the main\\u000a fatal complications of coronary atherosclerosis, i.e., sudden cardiac death and chronic heart failure, which mainly results\\u000a from cardiac pump failure. Are dietary

Michel de Lorgeril; Patricia Salen

178

Macrophage Activation in Atherosclerosis: Pathogenesis and Pharmacology of Plaque Rupture  

Microsoft Academic Search

Atherosclerosis is still an important disease. It accounts for 39% of deaths in the U.K. and 12 million U.S citizens have atherosclerosis-associated disease. Atherosclerosis may exert clinical effects by slow narrowing, producing stable angina or dramatic rupture, producing acute coronary syndromes such as unstable angina or myocardial infarction and death. Macrophages are abundant in ruptured atherosclerotic plaques. Macrophages are innate

J. J. Boyle

2005-01-01

179

Experimental models investigating the inflammatory basis of atherosclerosis  

Microsoft Academic Search

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

Ahmed Soliman; Patrick Kee

2008-01-01

180

Correlating corneal arcus with atherosclerosis in familial hypercholesterolemia  

PubMed Central

Background A relationship between corneal arcus and atherosclerosis has long been suspected but is controversial. The homozygous familial hypercholesterolemia patients in this study present a unique opportunity to assess this issue. They have both advanced atherosclerosis and corneal arcus. Methods This is a cross-sectional study of 17 patients homozygous for familial hypercholesterolemia presenting to the Clinical Center of the National Institutes of Health. Plasma lipoproteins, circumferential extent of arcus, thoracic aorta and coronary calcific atherosclerosis score, and Achilles tendon width were measured at the National Institutes of Health. Results Patients with corneal arcus had higher scores for calcific atherosclerosis (mean 2865 compared to 412), cholesterol-year score (mean 11830 mg-yr/dl compared to 5707 mg-yr/dl), and Achilles tendon width (mean 2.54 cm compared to 1.41 cm) than those without. Corneal arcus and Achilles tendon width were strongly correlated and predictive of each other. Although corneal arcus was correlated with calcific atherosclerosis (r = 0.67; p = 0.004), it was not as highly correlated as was the Achilles tendon width (r = 0.855; p < 0.001). Conclusion Corneal arcus reflects widespread tissue lipid deposition and is correlated with both calcific atherosclerosis and xanthomatosis in these patients. Patients with more severe arcus tend to have more severe calcific atherosclerosis. Corneal arcus is not as good an indicator of calcific atherosclerosis as Achilles tendon thickness, but its presence suggests increased atherosclerosis in these hypercholesterolemic patients.

Zech, Loren A; Hoeg, Jeffery M

2008-01-01

181

Oral FTY720 administration induces immune tolerance and inhibits early development of atherosclerosis in apolipoprotein E-deficient mice.  

PubMed

Orally administered immunomodulatory drugs have recently demonstrated the ability to induce an oral tolerance via inhibition of effector T cells and induction of certain subsets of regulatory T cells (Tregs) which have the potential to prevent several autoimmune diseases. In the present study, we hypothesized that short-term, low-dose, oral FTY720 administration may induce latency-associated peptide (LAP) Tregs and CD4(+) Foxp3(+) Tregs in atherogenesis, potentially resulting in remission of early development of atherosclerosis in apolipoprotein E-deficient (APOE(-/-)) mice. FTY720 was orally administered to APOE(-/-) mice 4 weeks of age on a high-cholesterol diet and atherosclerosis was assessed at 8 weeks of age. Oral administration of FTY720 significantly reduced atherosclerotic lesion formation compared with control mice. We observed a significant increase in LAP(+) and Foxp3(+) cells in the CD4+T-cell population of FTY720-treated mice in association with increased production of the anti-inflammatory cytokine transforming growth factor-? (TGF-?) as well as suppressed T-helper type 1 immune responses. Our findings reveal that short-term, low-dose oral FTY720 treatment had great benefits in inhibiting early development of atherosclerosis in mice via induction of a regulatory T-cell response and inhibition of effector T responses. These findings suggest that oral immune modulation may represent an attractive therapeutic approach to atherosclerosis. PMID:22697071

Huang, K; Li, S Q; Wang, W J; Liu, L S; Jiang, Y G; Feng, P N; Wang, Y Q; Wang, S M

182

Reversibility of atherosclerosis--evolving perspectives from two arterial imaging clinical trials: the cholesterol lowering atherosclerosis regression study and the monitored atherosclerosis regression study.  

PubMed

The Cholesterol Lowering Atherosclerosis Study (CLAS) and the Monitored Atherosclerosis Regression Study (MARS) are serial arterial imaging clinical trials that have explored the reversibility of atherosclerosis with lipid-lowering therapy in native coronary, carotid, and femoral arterial beds, as well as in coronary artery bypass grafts. Results demonstrate that progression of atherosclerosis can be reduced in all these vascular beds. Evolving data indicate that coronary lesions > or = 50% diameter stenosis (%S) at baseline respond more readily to lipid-lowering therapy than lesions <50%S. In addition, lipoproteins may have a differential effect on coronary lesion progression according to lesion size, with triglyceride-rich lipoproteins playing an important role in the progression of lesions <50%S. Limited data indicate that progression of atherosclerosis in women may be more responsive to lipid-lowering therapy than in men, and that estrogen replacement may enhance the anti-atherosclerosis effects of lipid lowering. Longitudinal measurements of carotid artery far wall intima-media thickness (IMT) with B-mode ultrasonography in CLAS and MARS indicate that carotid atherosclerosis at a stage before lesions intrude into the vessel lumen can be reduced by lipid-lowering therapy. Together, CLAS and MARS data indicate that the spectrum from very early lesions confined to the arterial wall to established lesions late in the atherosclerotic process can be reversed with lipid-lowering therapy. PMID:8907211

Hodis, H N

1995-01-01

183

Wholegrain intake and carotid artery atherosclerosis in a multiethnic cohort: the Insulin Resistance Atherosclerosis Study13  

Microsoft Academic Search

Background: Whole-grain intake has been shown to be inversely associated with cardiovascular events, but an association with ath- erosclerosis is less well established. Objective: We sought to evaluate the association of whole-grain intake with carotid intimal medial thickness (IMT) and IMT pro- gression in a multiethnic cohort. Design: This study evaluated 1178 participants in the Insulin Re- sistance Atherosclerosis Study.

Philip B Mellen; Angela D Liese; Janet A Tooze; Mara Z Vitolins; Lynne E Wagenknecht; David M Herrington

184

Life-course socioeconomic positions and subclinical atherosclerosis in the multi-ethnic study of atherosclerosis  

Microsoft Academic Search

A major limitation of past work on the social patterning of atherosclerosis has been the reliance on measures of neighborhood or individual-level socioeconomic position (SEP) assessed at a single point in time in adulthood. Risk of chronic disease is thought to accumulate throughout the life-course, so the use of a measure for a single point in time may result in

Emily T. Lemelin; Ana V. Diez Roux; Tracy G. Franklin; Mercedes Carnethon; Pamela L. Lutsey; Hanyu Ni; Ellen O'Meara; Sandi Shrager

2009-01-01

185

Accelerated atherosclerosis in patients with Wegener's granulomatosis  

PubMed Central

Background: Several autoimmune disorders are complicated by excess cardiovascular disease. In addition to traditional risk factors, non-traditional risk factors such as endothelial activation and excessive vascular remodelling might be determinants of the progression of atherosclerosis in patients with an autoimmune disease. Objective: To evaluate whether patients with Wegener's granulomatosis (WG) have an increased prevalence of atherosclerosis and to determine predisposing factors. Methods: 29 WG patients (19 men; mean (SD) age, 53 (14) years) with inactive disease and 26 controls (16 men; age 53 (15) years) were studied. Common carotid intima–media thickness (IMT) was measured by ultrasound. In all individuals traditional risk factors for cardiovascular disease were determined. High sensitivity C reactive protein (hsCRP) was measured. Endothelial activation was assessed by measuring thrombomodulin, vascular cell adhesion molecule-1, and von Willebrand factor. As a marker of vascular remodelling matrix metalloproteinases (MMP-3 and MMP-9) and TIMP-1 were measured. Results: IMT was increased in WG patients compared with controls (p<0.05). No differences in traditional risk factors and endothelial activation markers between patients and controls were found. Levels of hsCRP, MMPs, and TIMP-1 were increased in WG patients (p<0.05). Conclusions: Increased IMT found in WG patients cannot be explained by an increased prevalence of traditional risk factors. Although endothelial activation markers in WG patients with inactive disease were not increased, the raised levels of hsCRP, MMPs, and TIMP-1 suggest that enhanced inflammation and excessive vascular remodelling are contributing factors in the development of accelerated atherosclerosis in WG.

de Leeuw, K; Sanders, J; Stegeman, C; Smit, A; Kallenberg, C; Bijl, M

2005-01-01

186

IL-33 reduces the development of atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory disease of the vasculature commonly leading to myocardial infarction and stroke. We show that IL-33, which is a novel IL-1–like cytokine that signals via ST2, can reduce atherosclerosis development in ApoE?/? mice on a high-fat diet. IL-33 and ST2 are present in the normal and atherosclerotic vasculature of mice and humans. Although control PBS-treated mice developed severe and inflamed atherosclerotic plaques in the aortic sinus, lesion development was profoundly reduced in IL-33–treated animals. IL-33 also markedly increased levels of IL-4, -5, and -13, but decreased levels of IFN? in serum and lymph node cells. IL-33 treatment also elevated levels of total serum IgA, IgE, and IgG1, but decreased IgG2a, which is consistent with a Th1-to-Th2 switch. IL-33–treated mice also produced significantly elevated antioxidized low-density lipoprotein (ox-LDL) antibodies. Conversely, mice treated with soluble ST2, a decoy receptor that neutralizes IL-33, developed significantly larger atherosclerotic plaques in the aortic sinus of the ApoE?/? mice compared with control IgG-treated mice. Furthermore, coadministration of an anti–IL-5 mAb with IL-33 prevented the reduction in plaque size and reduced the amount of ox-LDL antibodies induced by IL-33. In conclusion, IL-33 may play a protective role in the development of atherosclerosis via the induction of IL-5 and ox-LDL antibodies.

Miller, Ashley M.; Xu, Damo; Asquith, Darren L.; Denby, Laura; Li, Yubin; Sattar, Naveed; Baker, Andrew H.; McInnes, Iain B.; Liew, Foo Y.

2008-01-01

187

Alexander I. Ignatowski: a pioneer in the study of atherosclerosis.  

PubMed

In 1908, Alexander I. Ignatowski (1875-1955) published his pioneering work that first revealed a relationship between cholesterol-rich food and experimental atherosclerosis. This early experimental work paved a way to the metabolic study of the mechanism of atherosclerosis. Herein, we present a brief account of Ignatowski's work and life. PMID:23914012

Konstantinov, Igor E; Jankovic, Gradimir M

2013-01-01

188

[Helicobacter pylori and atherosclerosis. A review of the literature].  

PubMed

Several studies have investigated potential role of Helicobacter pylori (Hp) in the pathogenesis of atherosclerosis. Postulated mechanisms are various, even though results are still controversial. Here we propose an overview of actual knowledge about this topic, comparing studies in favour with those against the relationship between Hp and atherosclerosis. PMID:19350802

Franceschi, Francesco; Navarese, Eliano Pio; Mollo, Roberto; Giupponi, Bianca; De Marco, Guido; Merra, Giuseppe; Gasbarrini, Giovanni; Silveri, Nicolò Gentiloni

2009-02-01

189

Carotid Atherosclerosis Is Associated with Brain Atrophy in Japanese Elders  

Microsoft Academic Search

Background: The relation between atherosclerosis and brain atrophy remains unclear in patients with risk factors for cardiovascular diseases. Objective: This study was performed to clarify the relation between brain atrophy and carotid atherosclerosis. Methods: A total of 142 patients (78 women and 64 men, mean age 74 years) with no neurologic disturbances were studied. Brain atrophy was evaluated on the

Tesseki Kin; Shigeru Yamano; Ritsuro Sakurai; Miyuki Kajitani; Yumiko Okahashi; Noriko Nishiura; Yoshihiko Saito; Satoshi Ueno

2007-01-01

190

Correlating corneal arcus with atherosclerosis in familial hypercholesterolemia  

Microsoft Academic Search

BACKGROUND: A relationship between corneal arcus and atherosclerosis has long been suspected but is controversial. The homozygous familial hypercholesterolemia patients in this study present a unique opportunity to assess this issue. They have both advanced atherosclerosis and corneal arcus. METHODS: This is a cross-sectional study of 17 patients homozygous for familial hypercholesterolemia presenting to the Clinical Center of the National

Loren A Zech Jr; Jeffery M Hoeg

2008-01-01

191

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

192

Applications of stenting for intracranial atherosclerosis.  

PubMed

Intracranial atherosclerosis presents a therapeutic challenge to medical and surgical physicians alike. Despite maximal medical therapy, the stroke rate from this disease is still high, especially when arterial stenosis is severe and patients are symptomatic. Open surgical therapy has yet to be shown to be a more efficacious treatment than medical therapy alone, largely due to the relatively high rates of perioperative complications. Angioplasty has a similar fate, with the risk of periprocedural complications outweighing the overall benefit of treatment. With the advent of stents for use in intracranial vasculature, new hope has arisen for the treatment of intracranial atherosclerosis. The NEUROLINK system, the drug-eluting stents Taxus and Cypher, the flexible Wingspan stent, the Apollo stent, and the Pharos stent have all been used in various prospective and retrospective clinical studies with varying technical and clinical results. The authors' objective is to review and loosely compare the data presented for each of these stenting systems. While the Wingspan stent appears to have somewhat of an advantage with regard to technical success in comparison with the other stenting systems, the clinical follow-up time of its studies is too short to properly compare its complication rates with those of other stents. Before we continue to move forward with stenting for intracranial stenosis, a randomized prospective trial is ultimately needed to directly compare intracranial stenting to medical therapy. PMID:21631216

Ding, Dale; Liu, Kenneth C

2011-06-01

193

Nonalcoholic fatty liver disease and atherosclerosis.  

PubMed

Atherosclerosis is a complex inflammatory disease comprising multiple plaque phenotypes. The development of advanced atheromatous plaques with necrotic core represents the result of the invasion of lipid pools by macrophages. The release of activated proteolytic enzymes degrades the surrounding tissue and contributes to the formation of vulnerable plaque. Thinning of the fibrous cap and necrotic core expansion are considered to be critical for the progression toward plaque rupture and acute thrombosis. The pathogenic mechanisms leading the progression of atherosclerotic lesions are various and involve endothelial cells, inflammatory cells, and platelets. Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis (NASH) and may progress to cirrhosis and hepatocellular carcinoma. The prevalence of this pathology is quite high in the general population and is one of the most important causes of liver-related morbidity and mortality in children. NAFLD is considered the hepatic feature of the metabolic syndrome and this has stimulated interest in its possible role in the atherosclerosis development. Clinical observations indicated that NAFLD might be an independent risk factor for coronary artery disease. Moreover, NASH may increase atherosclerotic and cardiovascular risks by local overexpression of inflammatory mediators, endothelial damage, and regulators of blood pressure. NASH development is correlated with hepatic progenitor cell activation and the release of proatherogenic adipokines. These aspects suggest the necessity for an early therapeutic intervention in NASH patients, not only for ameliorating the liver injury, but also for improving the systemic proatherogenic state. PMID:23073871

Gaudio, Eugenio; Nobili, Valerio; Franchitto, Antonio; Onori, Paolo; Carpino, Guido

2012-10-01

194

Quantum dot mediated imaging of atherosclerosis  

PubMed Central

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

2009-01-01

195

Collateral circulation in symptomatic intracranial atherosclerosis  

PubMed Central

Collateral circulation in intracranial atherosclerosis has never been systematically characterized. We investigated collaterals in a multicenter trial of symptomatic intracranial atherosclerotic disease. Baseline angiography was reviewed for information on collaterals in stenoses of the internal carotid, middle cerebral, vertebral, and basilar arteries. A battery of angiographic scales was utilized to evaluate lesion site, arterial patency, antegrade flow, downstream territorial perfusion, and collateral circulation, blinded to all other data. Collateral circulation was adequately available for analysis in 287/569 (50%) subjects with proximal arterial stenoses ranging from 50% to 99%. Extent of collaterals was absent or none in 69%, slow or minimal in 10%, more rapid, yet incomplete perfusion of territory in 7%, complete but delayed perfusion in 11%, and rapid, complete collateral perfusion in 4%. Extent of collateral flow correlated with percentage of stenosis (P<0.0001), with more severe stenoses exhibiting greater compensation via collaterals. Overall, collateral grade increased with diminished antegrade flow across the lesion (thrombolysis in myocardial ischemia) and resultant downstream perfusion (thrombolysis in cerebral infarction) (both P<0.001). Our findings provide the initial detailed description of collaterals across a variety of stenoses, suggesting that collateral perfusion is a pivotal component in pathophysiology of intracranial atherosclerosis and implicating the need for further evaluation in ongoing studies.

Liebeskind, David S; Cotsonis, George A; Saver, Jeffrey L; Lynn, Michael J; Cloft, Harry J; Chimowitz, Marc I

2011-01-01

196

Photoangioplasty: new applications of photodynamic therapy in atherosclerosis  

NASA Astrophysics Data System (ADS)

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

Rockson, Stanley G.

2000-05-01

197

Atherosclerosis and Rheumatoid Arthritis: More Than a Simple Association  

PubMed Central

In the last decades a large amount of evidence linked rheumatoid arthritis (RA) to atherosclerosis. In fact, RA patients have an increased risk of cardiovascular events that is not fully explained by other classic cardiovascular risk factors. RA and atherosclerosis may share several common pathomechanisms and inflammation undoubtedly plays a primary role. The proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, involved in the pathogenesis of RA, are also independently predictive of subsequent cardiovascular disease (CVD). In RA, inflammation alters HDL constituents and the concentration of LDL and HDL, thus facilitating atherosclerosis and CVD events. On the other hand, also the increase of oxidative processes, frequently observed in RA, induces atherosclerosis. Interestingly, some genetic polymorphisms associated with RA occurrence enhance atherosclerosis, however, other polymorphisms associated with RA susceptibility do not increase CVD risk. Several other mechanisms may influence atherosclerotic processes in RA. Moreover, atherosclerosis may be directly mediated also by underlying autoimmune processes, and indirectly by the occurrence of metabolic syndrome and impaired physical activity. Finally, the effects of RA therapies on cardiovascular system in general and on atherosclerosis in particular are really wide and different. However, the starting point of every RA treatment is that disease control, or better remission, is the best way we have for the reduction of CVD occurrence.

Cavagna, Lorenzo; Boffini, Nicola; Cagnotto, Giovanni; Inverardi, Flora; Grosso, Vittorio; Caporali, Roberto

2012-01-01

198

Accelerated coronary atherosclerosis and H syndrome  

PubMed Central

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

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

2011-01-01

199

[Atherosclerosis treatment with etofibrate retard. New perspectives].  

PubMed

In a multicentric general-practice-study 2504 hyperlipoproteinemic patients were treated with etofibrate retard for 4 weeks. The drug was administered once daily in the evening. A highly significant decrease of the mean values of cholesterol around 18.4% and 27.6% resp., and of the mean triglycerides between 31.3% and 16.5% resp. were observed. The atherogenic index was reduced by 28%. The simultaneous, highly significant reduction of blood glucose and of uric acid levels as well as of blood pressure showed the comprising effects of etofibrate retard against the atherosclerosis and its risk factors. The excellent tolerance of the drug was stated by more than 99% of the patients treated. PMID:6618402

Degenring, F H; Schatton, W; Hotz, W

1983-08-11

200

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.

Koenen, Rory R; Weber, Christian

2011-01-01

201

Atherosclerosis risk factors in pigeon squabs  

SciTech Connect

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

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

1986-03-01

202

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

203

Lymphocytes and the Adventitial Immune Response in Atherosclerosis  

PubMed Central

Though much of the research on atherosclerosis has focused on the intimal accumulation of lipids and inflammatory cells, there is an increasing amount of interest in the role of the adventitia in coordinating the immune response in atherosclerosis. In this review of the contributions of the adventitia and adventitial lymphocytes to the development of atherosclerosis, we discuss recent research on the formation and structural nature of adventitial immune aggregates, potential mechanisms of crosstalk between the intima, media, and adventitia, specific contributions of B lymphocytes and T lymphocytes, and the role of the vasa vasorum and surrounding perivascular adipose tissue (PVAT). Furthermore, we highlight techniques for the imaging of lymphocytes in the vasculature.

Campbell, Kirsti A.; Lipinski, Michael J.; Doran, Amanda C.; Skaflen, Marcus D.; Fuster, Valentin; McNamara, Coleen A.

2012-01-01

204

Gene Deficiency in Activating Fc? Receptors Influences the Macrophage Phenotypic Balance and Reduces Atherosclerosis in Mice  

PubMed Central

Immunity contributes to arterial inflammation during atherosclerosis. Oxidized low-density lipoproteins induce an autoimmune response characterized by specific antibodies and immune complexes in atherosclerotic patients. We hypothesize that specific Fc? receptors for IgG constant region participate in atherogenesis by regulating the inflammatory state of lesional macrophages. In vivo we examined the role of activating Fc? receptors in atherosclerosis progression using bone marrow transplantation from mice deficient in ?-chain (the common signaling subunit of activating Fc? receptors) to hyperlipidemic mice. Hematopoietic deficiency of Fc? receptors significantly reduced atherosclerotic lesion size, which was associated with decreased number of macrophages and T lymphocytes, and increased T regulatory cell function. Lesions of Fc? receptor deficient mice exhibited increased plaque stability, as evidenced by higher collagen and smooth muscle cell content and decreased apoptosis. These effects were independent of changes in serum lipids and antibody response to oxidized low-density lipoproteins. Activating Fc? receptor deficiency reduced pro-inflammatory gene expression, nuclear factor-?B activity, and M1 macrophages at the lesion site, while increasing anti-inflammatory genes and M2 macrophages. The decreased inflammation in the lesions was mirrored by a reduced number of classical inflammatory monocytes in blood. In vitro, lack of activating Fc? receptors attenuated foam cell formation, oxidative stress and pro-inflammatory gene expression, and increased M2-associated genes in murine macrophages. Our study demonstrates that activating Fc? receptors influence the macrophage phenotypic balance in the artery wall of atherosclerotic mice and suggests that modulation of Fc? receptor-mediated inflammatory responses could effectively suppress atherosclerosis.

Mallavia, Benat; Oguiza, Ainhoa; Lopez-Franco, Oscar; Recio, Carlota; Ortiz-Munoz, Guadalupe; Lazaro, Iolanda; Lopez-Parra, Virginia; Egido, Jesus; Gomez-Guerrero, Carmen

2013-01-01

205

Dolichoectatic vertebrobasilar dissecting aneurysm originating from atherosclerosis: an autopsy case.  

PubMed

We herein report an unusual case of profound brain infarction of the posterior circulation due to a dolichoectatic vertebrobasilar dissecting aneurysm (DVDA) originating from atherosclerosis. On autopsy, diffuse atherosclerosis was observed with a multi-fusiform aneurysm measuring 1 to 2 cm in diameter ranging from the left vertebral artery to the basilar artery. The microscopic findings of the aneurysm revealed severe stenosis of the artery caused by intimal thickening, intimal flap formation and thrombosis, indicating the presence of a dissecting aneurysm originating from atherosclerosis. The DVDA observed in this case was considered to be slowly progressive and associated with the development of atherosclerosis. The etiology of structural destabilization in patients with DVDA involves rupture of the internal elastic lamina, which is dislodged by massive hematomas that form atheromatous lesions. PMID:23955618

Isa, Katsunori; Sakima, Hirokuni; Kosuge, Noritake; Kokuba, Kazuhito; Goya, Yoshino; Nakachi, Koh; Ishihara, Satoshi; Tokashiki, Takashi; Ohya, Yusuke; Saio, Masanao

2012-03-01

206

Oxidized low density lipoprotein, stem cells, and atherosclerosis  

PubMed Central

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

2012-01-01

207

Earlobe creases and coronary atherosclerosis. The view from forensic pathology.  

PubMed

In several clinical studies, the diagonal earlobe crease has been statistically related to the presence of ischemic heart disease. Only one study of a relatively small number of hospitalized patients attempts to relate the earlobe crease with amount of stenotic coronary atherosclerosis demonstrated at necropsy. We examined the relationship between the degree of coronary atherosclerosis and the presence of a diagonal earlobe crease in 800 consecutive autopsies performed for medicolegal reasons and thus including a wide spectrum of subjects. Statistical analysis by the chi 2 test demonstrated a positive correlation (p less than 0.01) between the presence of the diagonal earlobe crease and obstructive coronary atherosclerosis narrowing on at least one major coronary artery greater than 75%. We conclude that the autopsy findings support the clinical observations that the diagonal earlobe crease is a cutaneous sign of obstructive coronary atherosclerosis and that the sign should be used accordingly. PMID:3578215

Cumberland, G D; Riddick, L; Vinson, R

1987-03-01

208

Atherosclerosis in Autoimmune Rheumatic Diseases—Mechanisms and Clinical Findings  

Microsoft Academic Search

Atherosclerosis is one of the major entities leading to morbidity and mortality in the western world. It is known now that\\u000a atherosclerosis cannot be explained merely by the presence of the Framingham traditional risk factors and that autoimmunity\\u000a takes a significant role in its pathogenesis. It is also known that individuals with autoimmune diseases demonstrate increased\\u000a incidence of cardiovascular manifestations

Hasya Zinger; Yaniv Sherer; Yehuda Shoenfeld

2009-01-01

209

Subclinical coronary atherosclerosis and neighbourhood deprivation in an urban region  

Microsoft Academic Search

Inhabitants of deprived neighbourhoods are at higher risk of coronary heart disease. In this study we investigate the hypothesis\\u000a that social inequalities at neighbourhood level become already manifest in subclinical coronary atherosclerosis, as defined\\u000a by electron-beam computed tomography derived measures. Coronary artery calcification was assessed as a marker of atherosclerosis\\u000a in a population based sample of 4301 men and women

Nico Dragano; Barbara Hoffmann; Andreas Stang; Susanne Moebus; Pablo E. Verde; Simone Weyers; Stefan Möhlenkamp; Axel Schmermund; Klaus Mann; Karl-Heinz Jöckel; Raimund Erbel; Johannes Siegrist

2009-01-01

210

Silent Myocardial Ischemia in Patients With Symptomatic Intracranial Atherosclerosis  

Microsoft Academic Search

Background and Purpose—Optimization of coronary risk evaluation in stroke patients has been encouraged. The relationship between symptomatic intracranial atherosclerosis and occult coronary artery disease (CAD) has not been evaluated sufficiently. We aimed to investigate the prevalence of silent myocardial ischemia in patients with symptomatic intracranial atherosclerosis and to identify factors associated with its presence. Methods—From 186 first-ever transient ischemic attack

2009-01-01

211

Association between arterial stiffness and atherosclerosis: the Rotterdam Study  

Microsoft Academic Search

BACKGROUND AND PURPOSE: Studies of the association between arterial\\u000a stiffness and atherosclerosis are contradictory. We studied stiffness of\\u000a the aorta and the common carotid artery in relation to several indicators\\u000a of atherosclerosis. METHODS: This study was conducted within the Rotterdam\\u000a Study in >3000 elderly subjects aged 60 to 101 years. Aortic stiffness was\\u000a assessed by measuring carotid-femoral pulse wave velocity,

Popele van N. M-L; Diederick E. Grobbee; Michiel L. Bots; Roland Asmar; Jirar Topouchian; Robert S. Reneman; Arnold P. G. Hoeks; Kuip van der D. A; J. C. M. Witteman; A. Hofman

2001-01-01

212

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

213

Work-related psychosocial factors and carotid atherosclerosis  

Microsoft Academic Search

Background In order to better understand the role of work environment in the earlier stages of the cardiovascular disease process, we wanted to investigate the influence of work-related psychosocial factors on preclinical atherosclerosis. Methods Cross-sectional data was used to examine the association between psychological job demands, job decision latitude, and carotid atherosclerosis in 2658 vocationally-active Swedish men and women, ages

M Rosvall

2002-01-01

214

A 3 Adenosine Receptors, HIF-1 Modulation and Atherosclerosis  

Microsoft Academic Search

\\u000a Atherosclerosis, a multifactorial disease of the large arteries, is the major cause of heart disease and stroke worldwide.\\u000a Epidemiological studies have discovered several relevant environmental and genetic risk factors associated with this pathology.\\u000a Genomic and proteomic-based strategies in humans and rodent models have been instrumental in discovering genes and proteins\\u000a involved in the initiation and progression of atherosclerosis. Moreover multiple

Stefania Gessi; Stephen MacLennan; Edward Leung; Pier Andrea Borea

215

Current advances in understanding of immunopathology of atherosclerosis  

Microsoft Academic Search

The importance of the involvement of the immune system in the development and progression of atherosclerosis was first suggested\\u000a after the discovery of T cells in atherosclerotic lesions in 1990s. In order to be activated, T cell needs to be presented\\u000a with an antigen but how this occurs in atherosclerosis has been unclear until recently. Current research has recognised dendritic

Colin-John Perrins; Yuri V. Bobryshev

2011-01-01

216

Ambient Air Pollution and the Progression of Atherosclerosis in Adults  

Microsoft Academic Search

BackgroundCross-sectional studies suggest an association between exposure to ambient air pollution and atherosclerosis. We investigated the association between outdoor air quality and progression of subclinical atherosclerosis (common carotid artery intima-media thickness, CIMT).Methodology\\/Principal FindingsWe examined data from five double-blind randomized trials that assessed effects of various treatments on the change in CIMT. The trials were conducted in the Los Angeles area.

Nino Künzli; Michael Jerrett; Raquel Garcia-Esteban; Xavier Basagaña; Bernardo Beckermann; Frank Gilliland; Merce Medina; John Peters; Howard N. Hodis; Wendy J. Mack

2010-01-01

217

Bcl2 protein family: Implications in vascular apoptosis and atherosclerosis  

Microsoft Academic Search

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human\\u000a pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation\\u000a at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic\\u000a and proliferative responses of vascular cells during progression

Ozgur Kutuk; Huveyda Basaga

2006-01-01

218

Apolipoprotein E and atherosclerosis: insight from animal and human studies  

Microsoft Academic Search

Major advances have been made in our understanding of the role of apolipoprotein E (apoE) in the onset and development of atherosclerosis. Increasing evidence from both animal and human studies suggests that apoE is able to protect against atherosclerosis by: a) promoting efficient uptake of triglyceride-rich lipoproteins from the circulation; b) maintaining normal macrophage lipid homeostasis; c) playing a role

Jean Davignon; Jeffrey S. Cohn; Laurence Mabile; Lise Bernier

1999-01-01

219

Immune Activation Resulting from NKG2D/Ligand Interaction Promotes Atherosclerosis  

PubMed Central

Background The interplay between the immune system and abnormal metabolic conditions sustains and propagates a vicious feedback cycle of chronic inflammation and metabolic dysfunction that is critical for atherosclerotic progression. It is well established that abnormal metabolic conditions, such as dyslipidemia and hyperglycemia, cause various cellular stress responses that induce tissue inflammation and immune cell activation, which in turn exacerbate the metabolic dysfunction. However, molecular events linking these processes are not well understood. Methods and Results Tissues and organs of humans and mice with hyperglycemia and hyperlipidemia were examined for expression of ligands for NKG2D, a potent immune activating receptor expressed by several types of immune cells, and the role of NKG2D in atherosclerosis and metabolic diseases was probed using mice lacking NKG2D or by blocking NKG2D with monoclonal antibodies. NKG2D ligands were upregulated in multiple organs, particularly atherosclerotic aortae and inflamed livers. Ligand upregulation was induced in vitro by abnormal metabolites associated with metabolic dysfunctions. Using ApoE-/- mouse models we demonstrated that preventing NKG2D functions resulted in a dramatic reduction in plaque formation, suppressed systemic and organ inflammation mediated by multiple immune cell types, and alleviated abnormal metabolic conditions. Conclusions The NKG2D/ligand interaction is a critical molecular link in the vicious cycle of chronic inflammation and metabolic dysfunction that promotes atherosclerosis and might be a useful target for therapeutic intervention in the disease.

Xia, Mingcan; Guerra, Nadia; Sukhova, Galina K.; Yang, Kangkang; Miller, Carla K.; Shi, Guo-Ping; Raulet, David H.; Xiong, Na

2012-01-01

220

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.

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

221

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

PubMed Central

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 cytokines and express cell adhesion molecules, e.g. IL-8, IL-6, and VCAM-1, respectively, which may functionally regulate monocyte and macrophage adhesion and other processes during atherosclerosis. Factors that drive the inflammatory phenotype are not limited to cytokines but also include hemodynamic forces imposed on the blood vessel wall and intimate interaction of endothelial cells with SMCs, as well as changes in matrix composition in the vessel wall. However, it is critical to recognize that our understanding of the complex interaction of these multiple signal inputs has only recently begun to shed light on mechanisms that regulate the inflammatory SMC phenotype, primarily through models that attempt to recreate this environment ex vivo. The goal of this review is to summarize our current knowledge in this area and identify some of the key unresolved challenges and questions requiring further study.

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

2010-01-01

222

Stat3? mitigates development of atherosclerosis in apolipoprotein E-deficient mice.  

PubMed

The transcription factor Stat3 is an activator of systemic inflammatory genes. Two isoforms of Stat3 are generated by alternative splicing, Stat3? and Stat3?. The ? isoform lacks the transactivation domain but retains other functions, including dimerization and DNA binding. Stat3?-deficient mice exhibit elevated expression of systemic inflammatory genes and are hyperresponsive to lipopolysaccharide, suggesting that Stat3? functions predominantly as a suppressor of systemic inflammation. To test whether Stat3? deficiency would provoke pathologic effects associated with chronic inflammation, we asked whether selective removal of Stat3? would exacerbate the development of atherosclerosis in apolipoprotein E-deficient mice. In apoE(-/-)Stat3?(-/-) mice atherosclerotic plaque formation was significantly enhanced relative to apoE(-/-)Stat3?(+/+) controls. The ability of Stat3? deficiency to promote atherosclerosis was more pronounced in female mice, but could be unmasked in males by feeding a high fat diet. Infiltrating macrophages were not increased in aortas of apoE(-/-)Stat3?(-/-) mice. In contrast, the proportion of pro-inflammatory TH17 cells was significantly elevated in aortic infiltrates from apoE(-/-)Stat3?(-/-) mice, relative to paired apoE(-/-)Stat3?(+/+) littermates. These observations indicate that Stat3? can suppress pathologic sequelae associated with chronic inflammation. Our findings further suggest that in Stat3?-deficient mice the unopposed action of Stat3? may enhance atherogenesis in part by promoting differentiation of TH17 cells. PMID:23619910

Lee, Jihyun; Baldwin, William M; Lee, Chih-Yuan; Desiderio, Stephen

2013-04-26

223

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

PubMed

Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of 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

2013-04-07

224

Dendritic Cells in Human Atherosclerosis: From Circulation to Atherosclerotic Plaques  

PubMed Central

Background. Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory infiltrates predominantly consisting of monocytes/macrophages and activated T cells. More recent is the implication of dendritic cells (DCs) in the disease. Since DCs were demonstrated in human arteries in 1995, numerous studies in humans suggest a role for these professional antigen-presenting cells in atherosclerosis. Aim. This paper focuses on the observations made in blood and arteries of patients with atherosclerosis. In principal, flow cytometric analyses show that circulating myeloid (m) and plasmacytoid (p) DCs are diminished in coronary artery disease, while immunohistochemical studies describe increased intimal DC counts with evolving plaque stages. Moreover, mDCs and pDCs appear to behave differently in atherosclerosis. Yet, the origin of plaque DCs and their relationship with blood DCs are unknown. Therefore, several explanations for the observed changes are postulated. In addition, the technical challenges and discrepancies in the research field are discussed. Future. Future studies in humans, in combination with experimental animal studies will unravel mechanisms leading to altered blood and plaque DCs in atherosclerosis. As DCs are crucial for inducing but also dampening immune responses, understanding their life cycle, trafficking and function in atherosclerosis will determine potential use of DCs in antiatherogenic therapies.

Van Vre, Emily A.; Van Brussel, Ilse; Bosmans, Johan M.; Vrints, Christiaan J.; Bult, Hidde

2011-01-01

225

Atherosclerosis in the Erythrocebus patas, an old world monkey.  

PubMed Central

Fifty monkeys of the species Erythrocebus patas were fed a control monkey chow, a semi-synthetic diet containing 25% lard, or a semisynthetic diet containing 25% lard and 0.5% cholesterol for 2 years. The patas monkeys had naturally occurring atherosclerosis that was greatly accelerated by feeding a diet containing cholesterol. The atherosclerosis involved the aorta, predominantly the abdominal portion, the coronary arteries, and various peripheral vessels. Histologically, the atherosclerosis was characterized by intimal proliferative lesions associated with intra- and extracellular lipid deposition. Complicated lesions that developed after 2 years on the cholesterol-containing diet were associated with lipid crystals, necrosis, mineralization, and encroachment upon the media. Adventitial reactions characterized by increased vascularity and the presence of inflammatory cells were seen. All of these observations have been described as components of the human atherosclerotic disease process. The similarity of the patas monkey atherosclerosis to human atherosclerosis, the relatively large size and easy handling of the animals, and the fact that previous studies have shown the lipoproteins of both control and cholesterol-fed monkeys to resemble human lipoproteins all contribute to making the patas monkey a useful model for the study of experimental atherosclerosis. Images Figure 1-5 Figure 6 Figure 7-10 Figure 11 Figure 12

Mahley, R. W.; Johnson, D. K.; Pucak, G. J.; Fry, D. L.

1980-01-01

226

[Investigation of atherosclerosis in postmenopausal women: alteration of atherosclerosis-associated factors and vascular atherosclerosis by oral and transdermal estrogen replacement].  

PubMed

The incidence of cardiovascular disease (CVD) is lower in younger women than in men of the same age, but it rises after menopause, implicating aging as well as in part a decline in endogenous estrogen; however, whether hormone replacement therapy (HRT) in postmenopausal women might be effective for the prevention of CVD remains unknown. We evaluated the effects of oral conjugated equine estrogen (CEE) therapy and transdermal estradiol(E2) therapy on atherosclerosis-associated factors, such as circulating lipids, glucose, insulin, uric acid, and vascular inflammatory markers, and the vascular atherosclerosis assessment test, including blood pressure, brachial artery flow-mediated vasodilatation (FMD), brachial-ankle pulse wave velocity (baPWV), and carotid intima-media thickness (IMT), in postmenopausal women. Oral CEE therapy decreased total cholesterol, low-density lipoprotein (LDL) cholesterol, fasting blood glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-R), uric acid, and cell adhesion molecules (CAMs) levels and increased triglyceride, high-density lipoprotein (HDL) cholesterol, and C reactive protein (CRP) levels. Transdermal E2 therapy decreased uric acid and CAMs and had no effect on lipids, glucose metabolism, and CRP levels. In addition, oral CEE therapy increased FMD but did not change blood pressure, baPWV, and IMT. Transdermal E2 therapy decreased or had no effect on blood pressure, increased FMD, and decreased baPWV and IMT. Thus, measurement of atherosclerosis-associated factors and the vascular atherosclerosis assessment test might be useful for the assessment of atherosclerosis by HRT in postmenopausal women, and transdermal E2, but not oral CEE therapy, may have antiatherosclerotic effects by improving vascular atherosclerosis. PMID:23785796

Sumino, Hiroyuki; Murakami, Masami

2013-03-01

227

Risk Factors for Progression of Common Carotid Atherosclerosis: The Atherosclerosis Risk in Communities Study, 1987-1998  

Microsoft Academic Search

Intima-media thickness of the common carotid arteries is a marker of atherosclerosis and has been shown to be associated with prevalent and incident coronary heart disease and with coronary heart disease risk factors. The authors examined the association of baseline risk factors or change in risk factors with change in intima- media thickness over follow-up (1987-1998) in the Atherosclerosis Risk

Lloyd E. Chambless; Aaron R. Folsom; Vicki Davis; Richey Sharrett; Gerardo Heiss; Paul Sorlie; Moyses Szklo; George Howard; Gregory W. Evans

228

Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis  

NASA Astrophysics Data System (ADS)

Plaque angiogenesis promotes the growth of atheromas, but the functions of plaque capillaries are not fully determined. Neovascularization may act as a conduit for the entry of leukocytes into sites of chronic inflammation. We observe vasa vasorum density correlates highly with the extent of inflammatory cells, not the size of atheromas in apolipoprotein E-deficient mice. We show atherosclerotic aortas contain activities that promote angiogenesis. The angiogenesis inhibitor angiostatin reduces plaque angiogenesis and inhibits atherosclerosis. Macrophages in the plaque and around vasa vasorum are reduced, but we detect no direct effect of angiostatin on monocytes. After angiogenesis blockade in vivo, the angiogenic potential of atherosclerotic tissue is suppressed. Activated macrophages stimulate angiogenesis that can further recruit inflammatory cells and more angiogenesis. Our findings demonstrate that late-stage inhibition of angiogenesis can interrupt this positive feedback cycle. Inhibition of plaque angiogenesis and the secondary reduction of macrophages may have beneficial effects on plaque stability.

Moulton, Karen S.; Vakili, Khashayar; Zurakowski, David; Soliman, Mohsin; Butterfield, Catherine; Sylvin, Erik; Lo, Kin-Ming; Gillies, Stephen; Javaherian, Kashi; Folkman, Judah

2003-04-01

229

Pro-inflammatory genetic markers of atherosclerosis.  

PubMed

Atherosclerosis (AS) is a chronic, progressive, multifactorial disease mostly affecting large and medium-sized elastic and muscular arteries. It has formerly been considered a bland lipid storage disease. Currently, multiple independent pathways of evidence suggest this pathological condition is a peculiar form of inflammation, triggered by cholesterol-rich lipoproteins and influenced both by environmental and genetic factors. The Human Genome Project opened up the opportunity to dissect complex human traits and to understand basic pathways of multifactorial diseases such as AS. Population-based association studies have emerged as powerful tools for examining genes with a role in common multifactorial diseases that have a strong environmental component. These association studies often estimate the risk of developing a certain disease in carriers and non-carriers of a particular genetic polymorphism. Dissecting out the influence of pro-inflammatory genes within the complex pathophysiology of AS and its complications will help to provide a more complete risk assessment and complement known classical cardiovascular risk factors. The detection of a risk profile will potentially allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug or lifestyle modification; i.e. it will open the door to personalized medicine. PMID:23591672

Incalcaterra, Egle; Accardi, Giulia; Balistreri, Carmela Rita; Caimi, Gregorio; Candore, Giuseppina; Caruso, Marco; Caruso, Calogero

2013-06-01

230

Matrix metalloproteinase inhibition in atherosclerosis and stroke.  

PubMed

Matrix metalloproteinases (MMPs) are a family of tightly regulated, zinc-dependent proteases that degrade extracellular matrix (ECM), cell surface, and intracellular proteins. Vascular remodeling, whether as a function of normal physiology or as a consequence of a myriad of pathological processes, requires degradation of the ECM. Thus, the expression and activity of many MMPs are up-regulated in numerous conditions affecting the vasculature and often exacerbate vascular dysfunction. A growing body of evidence supports the rationale of using MMP inhibitors for the treatment of cardiovascular diseases, stroke, and chronic vascular dementia. This manuscript will examine promising targets for MMP inhibition in atherosclerosis and stroke, reviewing findings in preclinical animal models and human patient studies. Strategies for MMP inhibition have progressed beyond chelating the catalytic zinc to functional blocking antibodies and peptides that target either the active site or exosites of the enzyme. While the inhibition of MMP activity presents a rational therapeutic avenue, the multiplicity of roles for MMPs and the non-selective nature of MMP inhibitors that cause unintended side-effects hinder full realization of MMP inhibition as therapy for vascular disease. For optimal therapeutic effects to be realized, specific targets for MMP inhibition in these pathologies must first be identified and then attacked by potent and selective agents during the most appropriate timepoint. PMID:23865428

Roycik, M D; Myers, J S; Newcomer, R G; Sang, Q-X A

2013-09-01

231

Atherosclerosis: from biology to pharmacological treatment.  

PubMed

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

2012-09-01

232

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.

Riccioni, Graziano; Sblendorio, Valeriana

2012-01-01

233

Darapladib: an emerging therapy for atherosclerosis.  

PubMed

Despite a reduction in cardiovascular risk conferred by therapies that modify circulating lipids, a need remains for novel treatments to further decrease the occurrence of complications of atherosclerotic cardiovascular diseases. Lipoprotein-associated phospholipase-A(2) is an important regulator of lipid metabolism and inflammation that circulates with lipoprotein particles and is carried into the arterial wall with low-density lipoprotein particles during the progression of atherosclerosis. Within the vessel wall, lipoprotein-associated phospholipase-A(2) releases small molecules that stimulate macrophage recruitment and evolution to foam cells, leading to plaque vulnerability. Epidemiologic studies demonstrate that elevated circulating levels of lipoprotein-associated phospholipase-A(2) predict an increased risk of myocardial infarction and stroke, whereas histologic examination of diseased human coronary arteries reveals intense presence of the enzyme in atherosclerotic plaques that are prone to rupture. These considerations suggest lipoprotein-associated phospholipase-A(2) as a promising therapeutic target, and a specific inhibitor, darapladib, has been under development for this application. This review summarizes the completed preclinical and early phase clinical studies that underlie two recently commenced phase III clinical trials that will investigate the efficacy and safety of darapladib in nearly 13,000 individuals with coronary heart disease. When completed, these trials should provide important insights into the utility of darapladib to reduce myocardial infarction, stroke and cardiovascular death. PMID:20660537

Corson, Marshall A

2010-07-26

234

SIRT1 - an anti-inflammatory pathway at the crossroads between metabolic disease and atherosclerosis.  

PubMed

Atherosclerosis is a chronic inflammatory disease that is based on the interaction between inflammatory cell subsets and specific cells in the arterial wall. SIRT1 deacetylates histone and non-histone proteins and has been implicated in protective effects of caloric restriction on lifespan and metabolic pathways in yeast, nematodes, and mice. In the vasculature of rodents, SIRT1 mediates vasodilatation through the release of endothelial nitric oxide synthase-derived nitric oxide and scavenges reactive oxygen species. Using a genetic loss-of-function approach, SIRT1 has been shown to interfere with crucial steps of endothelial activation and atherogenesis by suppressing NF?B signaling: Partial SIRT1 deletion in ApoE-/- mice prevented expression of endothelial adhesion molecules thereby hampering the extravasation of circulating monocytes. In monocyte-derived macrophages SIRT1 deletion reduced the expression of the scavenger receptor lectin-like oxidized low-density lipoprotein receptor 1 (Lox-1) resulting in reduced foam cell formation and atherosclerosis. Moreover, it was reported that SIRT1 regulates the activity of liver X-receptor, thereby promoting ABCA1-driven reverse cholesterol transport in plaque-resident macrophages slowing foam cell formation. Finally, SIRT1 suppressed the expression of endothelial tissue factor, and thus exerted anti-thrombotic properties during induced carotid thrombosis in mice. These findings indicate protective effects of SIRT1 in atherogenesis and thrombosis at an experimental level and highlight the opportunity to translate this concept from bench to bedside. Indeed, SIRT1 activators are available and have been shown to exert beneficial effects at the preclinical level in obesity and type 2 diabetes mellitus (T2DM). SIRT1 activators are currently being evaluated in phase II clinical trials in patients with T2DM. The concept of SIRT1 activation appears a promising strategy for novel therapeutic approaches in patients with atherothrombosis. PMID:23259556

Winnik, Stephan; Stein, Sokrates; Matter, Christian M

2012-11-01

235

Anti-diabetic atherosclerosis effect of Prunella vulgaris in db/db mice with type 2 diabetes.  

PubMed

Diabetes mellitus is the leading cause of vascular complications such as atherosclerosis. This study was designed to investigate whether Prunella vulgaris (APV) would inhibit diabetic atherosclerosis in db/db mice with type 2 diabetes. The db/db mice were treated with high fat/high cholesterol (HFHC) diet and an aqueous extract of APV (100 and 200 mg/kg/day) for eight weeks to examine the long-term effect on metabolic abnormalities and diabetic atherosclerosis. APV treatment markedly lowered blood glucose and systolic blood pressure. The db/db mice experienced an increase in blood urea nitrogen as well as a decrease of creatinine clearance, the latter of which was restored by treatment with APV. Treatment with APV markedly decreased total plasma cholesterol, triglyceride, and LDL-cholesterol and also increased the HDL-cholesterol. In addition, malondialdehyde and TGF-?1 were decreased by treatment of APV. On the other hand, total NO level was decreased in db/db mice. However, the NO level was increased by treatment with APV, suggesting an association with vascular dysfunction. Vascular relaxation of aortic rings by acetylcholine or SNP-inducement was ameliorated by APV in a dose-dependent manner. Damage of vascular intima and hypertrophic of media were observed in db/db mice; however its dysfunction was improved by the treatment of APV. APV treatment significantly reduced the aortic expressions of ICAM-1, VCAM-1, ET-1, and nitrotyrosine. Furthermore, expression of eNOS in aortic was remarkably increased by APV treatment. Taken together, APV suppressed hyperglycemia and diabetic vascular dysfunction in HFHC diet-db/db mice. The present data suggest that Prunella vulgaris may prevent development of diabetic atherosclerosis. PMID:22928826

Hwang, Sun Mi; Kim, Jin Sook; Lee, Yun Jung; Yoon, Jung Joo; Lee, So Min; Kang, Dae Gill; Lee, Ho Sub

2012-01-01

236

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.

Rader, Daniel J.

2011-01-01

237

Serotonin reuptake inhibitor antidepressants (SSRIs) against atherosclerosis  

PubMed Central

Summary Selective serotonin reuptake inhibitors (SSRIs) are a class of drug widely used for treatment of mood disorders, including depression and cardiovascular disease. A search for related articles in the PubMed database was attempted. It covered studies, reports, reviews and editorials of the last 5 years. Pro-inflammatory cytokines, such as TNF-?, IL-1 and IL-6, stimulate central serotonin (5-HT) neurotransmission and are over-expressed in depression, which has been linked with hypothalamic-pituitary-adrenal axis (HPA) hyperactivity. They have also been implicated in the pathogenesis and progression of other stress-induced disorders, like myocardial infarction (MI) and coronary heart disease (CHD), as they seem to modulate cardiovascular function by a variety of mechanisms. Biological mechanisms like these may explain the link between depression and CHD. There are a variety of environmental factors as well as genetic factors that might influence the pharmacogenetics of antidepressant drugs. New generation selective serotonin reuptake inhibitor antidepressants (SSRIs) causing a reduced cardiovascular morbidity and mortality may be related to serotonin platelet abnormalities in depressed patients that are effectively treated by SSRIs. SSRIs such as fluoxetine, paroxetine, sertraline and citalopram are not only considered to be free from the cardiotoxicity of their predecessors but also to function as safe and efficacious agents against depression, platelet activation, atherosclerosis and development and prognosis of coronary heart disease. However, there is a need for more studies in order to establish the exact biochemical mechanisms that are responsible for these diseases and the immunoregulatory effects of chronic use of SSRI medications.

Wozniak, Greta; Toska, Aikaterini; Saridi, Maria; Mouzas, Odysseas

2011-01-01

238

Coronary and carotid atherosclerosis: similarities and differences.  

PubMed

Although a relationship is commonly accepted between coronary and carotid arterial disease, suggesting that atherosclerosis is a systemic condition, the extent of this association and correspondence has not been fully elucidated. This review discusses recent research in this field and highlights areas for future study. The prevalence of severe carotid stenosis increases with prevalence of coronary stenosis, with the latter being found in a significant number of stroke patients, while those with carotid stenosis may be at higher risk of myocardial infarction than stroke. There also appear to be common risk factors (age, diabetes, hypertension, smoking and dyslipidemia), although the effects in both vascular systems may not be identical. Furthermore, while the degree of stenosis in the coronary artery has little ability to predict acute coronary syndrome, which is caused by local thrombosis from a ruptured or eroded plaque, severe carotid stenosis causing hypoperfusion is highly predictive of stroke, although this effect may be time-limited. This apparent difference in event mechanism in the two arteries is interesting as is the difference in the rate of development of collaterals. Overall, the evidence shows that a clear relationship exists between disease in the coronary and carotid arteries, since conventional risk factors and the extent of stenosis and/or previous events emanating from one artery have a strong bearing on the prevalence of events in the other artery. Nevertheless, the exact correspondence between the two arteries is unclear, with sometimes contradictory study results. More research is needed to identify the full extent of risk factors for severe stenosis and cardio- or cerebral vascular events, among which, inflammatory biomarkers such as hs-CRP and prior vascular events are likely to play a key role. PMID:23218802

Jashari, Fisnik; Ibrahimi, Pranvera; Nicoll, Rachel; Bajraktari, Gani; Wester, Per; Henein, Michael Y

2012-11-23

239

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

PubMed

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

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

2013-01-01

240

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

Microsoft Academic Search

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

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

1998-01-01

241

[Cyclooxygenase-2: a new therapeutic target in atherosclerosis?].  

PubMed

It is now widely accepted that atherosclerosis is a complex chronic inflammatory disorder of the arterial tree associated with several risk factors. From the initial phases to eventual rupture of vulnerable atherosclerotic plaques, a low-grade inflammation, also termed microinflammation, appears to play a key pathogenetic role. Systemic inflammatory markers (C reactive protein, cytokines adhesion molecules) also play a role in this process. Experimental and clinical evidence suggests that cyclooxygenase-2 (COX-2), an enzyme which catalyzes the generation of prostaglandins from arachidonic acid, also contributes to lesion formation. Recent reports by our group have demonstrated increased monocyte COX-2 activity and the production of prostaglandin E2 in relation to cardiovascular risk factors and subclinical atherosclerosis in asymptomatic subjects. Our findings support the notion that the COX-2/prostaglandin E2 axis may have a role, raising the question as to whether its selective inhibition might be an attractive therapeutic target in atherosclerosis. COX-2 inhibitors, collectively called "coxibs" (celecoxib, rofecoxib, valdecoxib, lumiracoxib, etc), held a promise as anti-inflammatory drugs without the some of the side effects of aspirin or non steroidal antiinflammatory agents. However, clinical studies raise several clinically relevant questions as to their beneficial role in atherosclerosis prevention, because of increased thrombogenicity and cardiovascular risk, and therefore coxibs should be restricted in atherosclerosis-prone patients. PMID:16792983

Páramo, José A; Beloqui, Oscar; Orbe, Josune

2006-05-27

242

Interleukin-4, Oxidative Stress, Vascular Inflammation and Atherosclerosis  

PubMed Central

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

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

2010-01-01

243

Telomeres, atherosclerosis, and the hemothelium: the longer view.  

PubMed

The model we propose to explain the links between atherosclerosis and telomere dynamics (birth telomere length and its age-dependent shortening) in leukocytes takes cues from three facts: atherosclerosis is a disease of the vascular endothelium; the hematopoietic system and the vascular endothelium share a common embryonic origin; interindividual variation in leukocyte telomere length (LTL) in the general population has a genetic explanation. The model posits that LTL dynamics mirror telomere dynamics in hematopoietic stem cells (HSCs), where telomere length is an index of HSC reserves. Diminished HSC reserves at birth, their accelerated attrition rate afterward, or both are are reflected in shortened LTL during adulthood-a phenomenon that confers increased risk for atherosclerosis. We explain how telomere length in HSCs serves as both a biomarker of atherosclerosis and a determinant of its development. Our model comes down to this proposition: Shortened LTL predicts increased atherosclerotic risk because the injurious component of atherosclerosis exceeds the repair capacity of HSC reserves, which largely depend on HSC telomere length. PMID:22017444

Aviv, Abraham; Levy, Daniel

2011-10-17

244

Atherosclerosis and Thrombosis: Insights from Large Animal Models  

PubMed Central

Atherosclerosis and its thrombotic complications are responsible for remarkably high numbers of deaths. The combination of in vitro, ex vivo, and in vivo experimental approaches has largely contributed to a better understanding of the mechanisms underlying the atherothrombotic process. Indeed, different animal models have been implemented in atherosclerosis and thrombosis research in order to provide new insights into the mechanisms that have already been outlined in isolated cells and protein studies. Yet, although no model completely mimics the human pathology, large animal models have demonstrated better suitability for translation to humans. Indeed, direct translation from mice to humans should be taken with caution because of the well-reported species-related differences. This paper provides an overview of the available atherothrombotic-like animal models, with a particular focus on large animal models of thrombosis and atherosclerosis, and examines their applicability for translational research purposes as well as highlights species-related differences with humans.

Vilahur, Gemma; Padro, Teresa; Badimon, Lina

2011-01-01

245

IR Background Suppression Studies.  

National Technical Information Service (NTIS)

A brief description of the background suppression scheme is described, and results obtained using the defocussing technique are presented. It has been demonstrated that a background suppression ratio of two orders of magnitudes can be obtained.

O. Shepherd W. P. Reidy T. F. Zehnpfennig G. A. Vanasse A. T. Stair

1977-01-01

246

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

Federal Register 2010, 2011, 2012, 2013

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

2010-02-19

247

Effects of the antioxidant succinobucol (AGI1067) on human atherosclerosis in a randomized clinical trial  

Microsoft Academic Search

BackgroundThe antioxidant AGI-1067 was shown to reduce experimental atherosclerosis. The present study originally intended to study restenosis as a primary endpoint but was subsequently modified to primarily investigate the effects of AGI-1067 on coronary atherosclerosis.

Jean-Claude Tardif; Jean Grégoire; Philippe L. L’Allier; Reda Ibrahim; Todd J. Anderson; François Reeves; Erick Schampaert; Michel LeMay; Jacques Lespérance; Rob Scott; Marie-Claude Guertin; Marie-Luise Brennan; Stanley L. Hazen; Olivier F. Bertrand

2008-01-01

248

Food intake patterns associated with carotid artery atherosclerosis in the Insulin Resistance Atherosclerosis Study.  

PubMed

We aimed to identify food intake patterns that operate via haemostatic and inflammatory pathways on progression of atherosclerosis among 802 middle-aged adults with baseline and 5-year follow-up ultrasound measurements of common (CCA) and internal carotid artery (ICA) intimal medial thickness (IMT). Food intake was ascertained with an FFQ. We derived food patterns using reduced rank regression (RRR) with plasminogen activator inhibitor 1 and fibrinogen as response variables. We explored the impact of various food pattern simplification approaches. We identified a food pattern characterised by higher intakes of less healthful foods (low-fibre bread and cereal, red and processed meat, cottage cheese, tomato foods, regular soft drinks and sweetened beverages) and lower intakes of more healthful foods (wine, rice and pasta, meal replacements and poultry). The pattern was positively associated with mean CCA IMT at follow-up (P = 0.0032), a 1 sd increase corresponding to an increase of 13 mum higher CCA IMT at follow-up, adjusted for demographic and cardiovascular risk factors. With increasing pattern quartile (Q), the percentage change in CCA IMT increased significantly: Q1 0.8 %; Q2 3.2 %; Q3 8.6 %; Q4 7.9 % (P = 0.0045). No clear association with ICA IMT was observed. All simplification methods yielded similar results. The present results support the contention that a pro-inflammatory and pro-thrombotic dietary pattern increases the rate of coronary artery atherosclerosis progression, independent of traditional cardiovascular risk factors. RRR is a promising and robust tool for moving beyond the previous focus on nutrients or foods into research on the health effects of broader dietary patterns. PMID:20092665

Liese, Angela D; Nichols, Michele; Hodo, Denise; Mellen, Philip B; Schulz, Mandy; Goff, David C; D'Agostino, Ralph B

2010-01-22

249

Mice deficient in PKC? and apolipoprotein E display decreased atherosclerosis  

PubMed Central

Endothelial activation is a central initiating event in atheroma formation. Evidence from our laboratory and others has demonstrated links between activation of early growth response-1 (Egr-1) and atherosclerosis and also has demonstrated that activated protein kinase C (PKC) ?II is a critical upstream regulator of Egr-1 in response to vascular stress. We tested the role of PKC? in regulating key events linked to atherosclerosis and show that the aortas of apoE?/? mice display an age-dependent increase in PKC?II antigen in membranous fractions vs. C57BL/6 animals with a ?2-fold increase at age 6 wk and a ?4.5-fold increase at age 24 wk. Consistent with important roles for PKC? in atherosclerosis, a significant decrease in atherosclerotic lesion area was evident in PKC??/?/apoE?/? vs. apoE?/? mice by ?5-fold, in parallel with significantly reduced vascular transcripts for Egr-1 and matrix metalloproteinase (MMP)-2 antigen and activity vs. apoE?/? mice. Significant reduction in atherosclerosis of ?2-fold was observed in apoE?/? mice fed ruboxistaurin chow (PKC? inhibitor) vs. vehicle. In primary murine and human aortic endothelial cells, the PKC?-JNK mitogen-activated protein kinase pathway importantly contributes to oxLDL-mediated induction of MMP2 expression. Blockade of PKC? may be beneficial in mitigating endothelial perturbation and atherosclerosis.—Harja, E., Chang, J. S., Lu, Y., Leitges, M., Zou, Y. S., Schmidt, A. M., Yan, S.-F. Mice deficient in PKC? and apolipoprotein E display decreased atherosclerosis.

Harja, Evis; Chang, Jong Sun; Lu, Yan; Leitges, Michael; Zou, Yu Shan; Schmidt, Ann Marie; Yan, Shi-Fang

2009-01-01

250

Human nonspecific suppressive lymphokines  

Microsoft Academic Search

Since the term “lymphokine” first appeared in print over 20 years ago, a tremendous number of these soluble mediators of the immune system have been described. Within the past few years, many human nonspecific suppressive lymphokines have been identified. This review discusses the historical basis of immunologic suppression and suppressor factors. Later reports describing suppressive human lymphokines are then grouped

Michael T. Halpern

1991-01-01

251

Optical and Multimodality Molecular Imaging Insights Into Atherosclerosis  

PubMed Central

Imaging approaches that visualize molecular targets rather than anatomic structures aim to illuminate vital molecular and cellular aspects of atherosclerosis biology in vivo. Several such molecular imaging strategies are poised for rapid clinical application. This review describes the growing role of in vivo optical molecular imaging in atherosclerosis and highlights its ability to visualize atheroma inflammation, calcification, and angiogenesis. In addition we discuss advances in multimodality probes, both in the context of multimodal imaging as well as multifunctional, or “theranostic,” nanoparticles. This review highlights particular molecular imaging strategies that possess strong potential for clinical translation.

Jaffer, Farouc A.; Libby, Peter; Weissleder, Ralph

2009-01-01

252

In-111 platelet scintigraphy: carotid atherosclerosis and stroke  

SciTech Connect

An association between atherosclerosis of the internal carotid artery and ischemia or infarction of the ipsilateral cerebral hemisphere has been demonstrated by numerous radiographic and pathologic studies. The precise mechanism by which carotid atherosclerosis causes these problems, however, remains unclear. Several observations suggest that fibrin-platelet thrombi form on atherosclerotic plaques in the neck arteries and then embolize distally into the intracranial circulation. Unfortunately, platelet embolization does not adequately explain a variety of clinical and pathological findings in patients with cerebrovascular disease. This editorial will discuss these findings. It is obvious that the understanding of the role of platelets in the pathogenesis of ischemic cerebrvascular disease is far from complete.

Powers, W.J.

1984-05-01

253

Management of radiation-induced accelerated carotid atherosclerosis  

SciTech Connect

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

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

1987-07-01

254

[Correlation of some biochemical and coagulological parameters in carotid atherosclerosis].  

PubMed

It has been established positive correlation of the degree of stenosis and intima-media thickness of carotid arteries with the following biochemical parameters: total cholesterol, LDL cholesterol, Apo-B, Lp(a), triglycerides, hs-C-reactive protein(CRP), interleukines (IL-1beta and IL-6), fibrinogen, D-dimers. Negative correlation was stated with respect to HDL cholesterol, Apo-A-1, protein C. Relation between the parameters of the blood lipid spectre, proteins and mediators of inflammation as well as those of hemostasis enables us to approach pathophysiological mechanisms of carotid atherosclerosis, define the processes of inflammation and atherosclerosis. PMID:19996505

Akhvlediani, M V; Vorob'eva, E O; Emukhvari, M G; Sharashidze, N A; Kupreishvili, S B

2009-11-01

255

Non-Invasive Coronary Imaging for Atherosclerosis in HIV Infection  

PubMed Central

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

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

2011-01-01

256

Relationship of Chlamydia pneumoniae Infection to Severity of Human Coronary Atherosclerosis  

Microsoft Academic Search

Background—Infection with Chlamydia pneumoniaehas been postulated to play a pathogenic role in atherosclerosis. We examined the role of infection with C pneumoniae in relation to the extent of coronary atherosclerosis. Methods and Results—Coronary atherosclerosis was graded microscopically on a postmortem basis in a blinded fashion in 60 subjects as mild (n518) or severe (n542) atherosclerosis. Serum antibodies to C pneumoniae

Katharina Ericson; Tom G. P. Saldeen; Olle Lindquist; Carl Påhlson; Jawahar L. Mehta

257

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

258

Effects of Continuous Positive Airway Pressure on Early Signs of Atherosclerosis in Obstructive Sleep Apnea  

Microsoft Academic Search

Rationale: Obstructive sleep apnea (OSA) is associated with adverse cardiovascular outcomes, including myocardial infarction and stroke. Atherosclerosis is a key mechanism for these cardiovascular events. Recent cross-sectional studies showed the presence of early signs of atherosclerosis in patients with OSA who were free of comorbidities. Objectives: To determine the impact of treatment with continuous positive airway pressure (CPAP) on atherosclerosis.

Luciano F. Drager; Luiz A. Bortolotto; Adelaide C. Figueiredo; Eduardo M. Krieger; Geraldo Lorenzi-Filho

2007-01-01

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

Translating molecular discoveries into new therapies for atherosclerosis  

Microsoft Academic Search

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

Daniel J. Rader; Alan Daugherty

2008-01-01

261

The role of shear stress in the pathogenesis of atherosclerosis  

Microsoft Academic Search

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

Kristopher S Cunningham; Avrum I Gotlieb

2005-01-01

262

Quantitative coronary cineangiography for the study of atherosclerosis  

Microsoft Academic Search

Angiography is the definitive procedure for characterising the extent and course of coronary artery disease. We describe the methodology required to measure, with optimal resolving power, angiographic changes in coronary artery disease. We utilised recent technological developments in image digitization, storage and analysis. The measures of change quantified both diffuse and focal atherosclerosis. Frames from angiographic cine films were digitized

J. N. H. Brunt; G. F. Watts; B. Lewis; L. D. R. Smith; D. J. Coltart

1995-01-01

263

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

264

Atherosclerosis: The carbonic anhydrase, carbon dioxide, calcium concerted theory  

Microsoft Academic Search

Atherosclerosis is a dynamic multifaceted disease which affects the aorta and its major branches, characterized by the presence of lesions called atheromatous plaques. The plaque is a focal thickening of the intima caused by proliferation of smooth muscle cells, and the deposition of cholesterol, other lipids, hydroxyapatite and fibrous connective tissue. It is proposed that the determinant step of the

Wilbert Gamble

2006-01-01

265

trans-Fatty acids in the diet stimulate atherosclerosis  

Microsoft Academic Search

Epidemiological evidence has associated dietary trans-fatty acids (TFAs) with coronary heart disease. It is assumed that TFAs stimulate atherosclerosis, but this has not been proven. The purpose of this study was to determine the effects of consuming 2 concentrations of TFAs obtained from commercially hydrogenated vegetable shortening on atherosclerotic development in the presence or absence of elevated dietary cholesterol. Low-density

Chantal M. C. Bassett; Richelle S. McCullough; Andrea L. Edel; Thane G. Maddaford; Elena Dibrov; David P. Blackwood; Jose A. Austria; Grant N. Pierce

2009-01-01

266

The pathogenesis of atherosclerosis: a perspective for the 1990s  

Microsoft Academic Search

Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate

Russell Ross

1993-01-01

267

Inflammation in Atherosclerosis and Other Conditions: A Response to Danger  

Microsoft Academic Search

In the last few years atherosclerosis has been recognized as an inflammatory process. Assessment of low-grade inflammation with indexes like C-reactive protein (CRP) is considered indicative and potentially predictive for this disease. On the other hand, in a large number of clinical studies, a grade of microinflammation has been found to be associated with numerous other processes that may be

George Tsirpanlis

2005-01-01

268

DUCAT (Dutch inventory of invasive Coronary Atherosclerosis Treatments)  

Microsoft Academic Search

Het DUCAT (Dutch inventory of invasive Coronary Atherosclerosis Treatments) project had tot doel te bepalen hoe passend behandelbeslissingen (beleidsbeslissingen) zijn bij patiënten met vernauwing van een of meer kransslagaders rond het hart (coronairlijden). DUCAT bestond uit drie delen: a) bepaling van de passendheid van behandelindicaties door een panel van deskundigen, uitgaande van drie behandelvormen: coronaire-omleidingsoperatie (CABG), 'dotteren' (PTCA), en medicamenteuze

H. Rigter; A. P. Meijler; J. Scholma; J. McDonnel

1995-01-01

269

Increased LDL susceptibility to oxidation accelerates future carotid artery atherosclerosis  

PubMed Central

Background We analyzed the causal relationship between LDL susceptibility to oxidation and the development of new carotid artery atherosclerosis over a period of 5 years. We previously described the determinants related to a risk of cardiovascular changes determined in a Japanese population participating in the Niigata Study, which is an ongoing epidemiological investigation of the prevention of cardiovascular diseases. Methods We selected 394 individuals (169 males and 225 females) who underwent a second carotid artery ultrasonographic examination in 2001 - 2002 for the present study. The susceptibility of LDL to oxidation was determined as the photometric absorbance and electrophoretic mobility of samples that had been collected in 1996 - 1997. The measurements were compared with ultrasonographic findings obtained in 2001 - 2002. Results The multivariate-adjusted model showed that age (odds ratio (OR), 1.034; 95% confidence interval (95%CI), 1.010 - 1.059), HbA1c (OR, 1.477; 95%CI, 0.980 - 2.225), and photometric O/N (OR, 2.012; 95%CI, 1.000 - 4.051) were significant variables that could independently predict the risk of new carotid artery atherosclerosis. Conclusion The susceptibility of LDL to oxidation was a significant parameter that could predict new carotid artery atherosclerosis over a 5-year period, and higher susceptibility was associated with a higher incidence of new carotid artery atherosclerosis.

2012-01-01

270

Determinants of Early Atherosclerosis in Obese Children and Adolescents  

Microsoft Academic Search

Context: Obesity in childhood is associated with an increased mortality due to cardiovascular (CV) diseases in adulthood, inde- pendent of adult weight. Recent studies in children indicate that the atherosclerosis process starts at an early age and is linked to obesity. Objective: The aim of the study was to investigate determinants of increased carotid intima-media thickness (IMT), an early marker

Veronique Beauloye; Francis Zech; Hiep Tran; Thi Mong; Philippe Clapuyt; Marc Maes; Sonia M. Brichard

271

A central role for the endothelial NADPH oxidase in atherosclerosis  

Microsoft Academic Search

An increasing body of evidence has demonstrated that NADPH oxidase plays a critical role in several early steps leading toward the development of atherosclerosis. These effects appear to be carried out by both the ability of O2? to act as a small second messenger molecule, and potentially the oxidation of low density lipoprotein by O2?. We describe a model for

Jamie W. Meyer; Mark E. Schmitt

2000-01-01

272

Oversized vein grafts develop advanced atherosclerosis in hypercholesterolemic minipigs  

PubMed Central

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

2012-01-01

273

C-reactive protein in atherosclerosis: A causal factor?  

Microsoft Academic Search

Atherosclerosis is considered a to be multifactorial disease driven by inflammatory reactions. The process of inflammation also contributes to the pathogenesis of acute atherothrombotic events. C-reactive protein (CRP) is an acute phase protein and its concentration in serum reflects the inflammatory condition of the patient. Levels of CRP are consistently associated with cardiovascular disease (CVD) and predict myocardial infarctions and

Elaine Paffen; Moniek P. M. deMaat

2006-01-01

274

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

275

The Dietary Prevention of Atherosclerosis and Coronary Heart Disease.  

National Technical Information Service (NTIS)

Atherosclerosis is a disease in which fat deposits, fibrous tissue, blood elements, and calcium form a mushy, hard deposit within arterial walls. The result is a reduction of the lumen of arteries. In turn, this narrowing of the internal diameter of arter...

V. F. Froelicher

1976-01-01

276

TGF-betas and TGF-beta receptors in atherosclerosis  

Microsoft Academic Search

Based on diverse evidence in animals and humans, it has been hypothesized that atherosclerosis, and other injury-induced hyperplasias such as restenosis, may result from a failure in endogenous inhibitory systems that normally limit wound repair and induce regression of wound repair cells. A key defect in one of these inhibitory pathways, the TGF-beta system, has been identified and characterized in

T. A. McCaffrey

2000-01-01

277

Pulse Pressure and Coronary Atherosclerosis Progression in Postmenopausal Women  

Microsoft Academic Search

Pulse pressure, an index of large artery stiffness, has been associated with coronary events. However, mechanisms for this association remain unclear. In this study, we examined the relationship between pulse pressure and the progression of coronary atherosclerosis and the effects of hormone replacement therapy (HRT) on pulse pressure in postmenopausal women with angiographically confirmed coronary disease followed for 3.2 years

Girish V. Nair; David Waters; William Rogers; Glen J. Kowalchuk; Thomas D. Stuckey; David M. Herrington

2010-01-01

278

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

279

Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias.  

PubMed

A growing body of evidence demonstrates an association between vascular risk factors and Alzheimer's disease. This study investigated the frequency and severity of atherosclerotic plaques in the circle of Willis in Alzheimer's disease and multiple other neurodegenerative diseases. Semi-quantitative data from gross and microscopic neuropathological examinations in 1000 cases were analysed, including 410 with a primary diagnosis of Alzheimer's disease, 230 with synucleinopathies, 157 with TDP-43 proteinopathies, 144 with tauopathies and 59 with normal ageing. More than 77% of subjects with Alzheimer's disease had grossly apparent circle of Willis atherosclerosis, a percentage that was significantly higher than normal (47%), or other neurodegenerative diseases (43-67%). Age- and sex-adjusted atherosclerosis ratings were highly correlated with neuritic plaque, paired helical filaments tau neurofibrillary tangle and cerebral amyloid angiopathy ratings in the whole sample and within individual groups. We found no associations between atherosclerosis ratings and ?-synuclein or TDP-43 lesion ratings. The association between age-adjusted circle of Willis atherosclerosis and Alzheimer's disease-type pathology was more robust for female subjects than male subjects. These results provide further confirmation and specificity that vascular disease and Alzheimer's disease are interrelated and suggest that common aetiologic or reciprocally synergistic pathophysiological mechanisms promote both vascular pathology and plaque and tangle pathology. PMID:23204143

Yarchoan, Mark; Xie, Sharon X; Kling, Mitchel A; Toledo, Jon B; Wolk, David A; Lee, Edward B; Van Deerlin, Vivianna; Lee, Virginia M-Y; Trojanowski, John Q; Arnold, Steven E

2012-11-30

280

Chlamydia pneumoniae infections in mouse models: relevance for atherosclerosis research  

Microsoft Academic Search

Mouse models have been frequently used in the study of Chlamydia pneumoniae (also known as Chlamydophila pneumoniae) infections. This gram-negative obligate intracellular bacterium causes respiratory infections, followed by dissemination of the bacterium to various organs throughout the body, including cardiovascular tissues, supporting the current hypothesis of a relationship between C. pneumoniae and atherosclerosis. Recently, clinical trials evaluated the effect of

Martijn D. de Kruif; Tymen T. Kellera; Jacobus M. Ossewaardec

281

Arterial remodeling and atherosclerosis: miRNAs involvement  

Microsoft Academic Search

Cardiometabolic diseases (CMD) (such as atherosclerosis, diabetes, and hypertension) are the primary cause of death and disability in the Western world. Although lifestyle programs and therapeutic approaches have significantly reduced the socio-economic burden of CMD, a large number of events still cannot be avoided (the so called residual risk). Recent developments in genetics and genomics provide a platform for investigating

Manuela Quintavalle; Gianluigi Condorelli; Leonardo Elia

282

Effects of immunomodulatory drugs on plasma inflammatory markers in a rabbit model of atherosclerosis.  

PubMed

Atherosclerosis is a chronic disease of the arterial wall where both innate and adaptive immuno-inflammatory mechanisms are involved. Inflammatory cytokines are implicated in the development and progression of atherosclerotic lesions. Immunomodulatory therapies have been proposed for the treatment of atherosclerosis. Therefore, the aim of this study was to investigate the systemic anti-inflammatory and immunomodulatory effects of atorvastatin, cyclosporine A (CsA), and tacrolimus (FK506) on plasma inflammatory markers in atherosclerotic rabbits. Male New Zealand rabbits were randomized into five groups each of 12 animals. Standard diet-fed group served as control, and the cholesterol-fed group received a diet supplemented with 1% cholesterol alone, cholesterol?+?atorvastatin, cholesterol?+?FK506, and cholesterol?+?CsA. Serum levels of lipid profile parameters (triglycerides, cholesterol, and high-density lipoprotein) were measured using colorimetric methods. Serum levels of C-reactive protein (CRP), interleukin-6 (Il-6), and interferon-gamma (INF-?) were measured in all studied groups using ELISA techniques. Our results revealed a significant decrease (p?suppress elevated plasma inflammatory markers. Thus, low doses of these two immunomodulating drugs could not have generalized systemic anti-inflammatory or immunosuppressive effects. PMID:20960084

Houssen, Maha E; Haron, Mona M; Metwally, Sheren S; Ibrahim, Tarek M

2010-10-20

283

The Biology of Atherosclerosis: General Paradigms and Distinct Pathogenic Mechanisms Among HIV-Infected Patients  

PubMed Central

Complications of atherosclerosis, including myocardial infarction and stroke, are the leading cause of death and disability worldwide. Recent data strongly implicate cardiovascular death as a contributor to mortality among patients with human immunodeficiency virus (HIV) infection, with evidence suggesting increased incidence of atherosclerosis among these patients. Therefore, greater understanding of atherosclerotic mechanisms and how these responses may be similar or distinct in HIV-infected patients is needed. Key concepts in atherosclerosis are reviewed, including the evidence that inflammation and abnormal metabolism are major drivers of atherosclerosis, and connected to the current literature regarding atherosclerosis in the context of HIV.

Lo, Janet

2012-01-01

284

Correlation between the extent of coronary atherosclerosis and lipid profile.  

PubMed

Increased concentration of low density lipoprotein (LDL) cholesterol or decreased level of high density lipoprotein (HDL) cholesterol are important risk factors for coronary atherosclerosis. However, an independent association of triglycerides (TG) with atherosclerosis is uncertain. The aim of this prospective study was to evaluate the relationship between serum lipid levels and the extent of coronary atherosclerosis in patients with suspected coronary artery disease (CAD) and no previous myocardial infarction who were not treated with lipids lowering therapy or low-lipid diet. The study was conducted in 141 patients (53.6 +/- 7.8 years old; 32 female) who underwent a routine coronary angiography for CAD diagnosis. A modified angiographic Gensini Score (GS) was used to reflect the extent of coronary atherosclerosis. Fasting serum lipid concentrations were determined using cholesterol esterase/peroxidase (CHOD/PAP) enzymatic method for total cholesterol and its fractions and lipase glycerol kinase (GPO/PAP) enzymatic method TG evaluation. The association of Gensini Score with variables characterising lipid profile was analysed with the use of Pearson correlation (r co-efficient; p value). GS was positively correlated with total cholesterol (r = 0.404; p < 0.001), LDL cholesterol (r = 0.484; p < 0.001 ) and TG (r = 0.235; p = 0.005). There was a negative correlation between Gensini Score and HDL cholesterol (r = -0.396; p < 0.001). In angina pectoris patients with no previous myocardial infarction, the extent of coronary atherosclerosis is positively correlated with pro-atherogenic lipids, i.e. total cholesterol, LDL cholesterol and TG and negatively correlated with antiatherogenic HDL cholesterol. PMID:12841339

Tarchalski, Janusz; Guzik, Przemys?aw; Wysocki, Henryk

2003-04-01

285

Atherosclerosis in Systemic Sclerosis- A Systematic Review and Meta Analysis  

PubMed Central

Purpose Systemic sclerosis (SSc) is characterized by calcification, vasculopathy, and endothelial wall damage, all of which can increase the risk for atherosclerosis and cardiovascular disease. Our objective was to perform a systematic review and meta-analysis to determine if atherosclerosis is increased in patients with SSc compared to healthy individuals. Methods We performed a systematic search of studies published in PubMed and the Cochrane database up to May 2010, and reviewed recently-published abstracts. Two reviewers independently screened articles to identify studies comparing rates of atherosclerosis in SSc patients vs. healthy controls using one of the following modalities: angiography, doppler ultrasound to assess plaque and carotid intima-medial thickness (CIMT), computer tomography, magnetic resonance imaging, flow mediated dilation (FMD), ankle-brachial index, or autopsy findings. For CIMT and FMD, we computed a pooled estimate of the summary mean difference (MD) and explored predictors of CIMT using random-effects meta-regression. Results Of 3,156 articles initially identified, 33 were selected for the systematic review. Meta-analysis included 14 CIMT and 7 FMD studies. Compared to healthy controls, SSc patients had higher prevalence of coronary atherosclerosis, peripheral vascular disease, and cerebrovascular calcification. Meta-analysis showed SSc subjects had increased CIMT [MD 0.11mm (95% CI 0.05, 0.17), P=0.0006] and lower FMD [MD -3.07% (95%CI -5.44, -0.69), P=0.01]. There was marked heterogeneity between the studies, namely from variations in disease duration and difference in mean/median age between SSc and control groups. Conclusion Patients with SSc have increased atherosclerosis compared to healthy controls. Further studies should elucidate the mechanism of this increased risk.

Au, Karen; Singh, Manjit K.; Bodukam, Vijay; Bae, Sangmee; Maranian, Paul; Ogawa, Rikke; Spiegel, Brennan; McMahon, Maureen; Hahn, Bevra; Khanna, Dinesh

2011-01-01

286

Pathogen-Mediated Inflammatory Atherosclerosis Is Mediated in Part via Toll-Like Receptor 2Induced Inflammatory Responses  

Microsoft Academic Search

Studies in humans have established that polymorphisms in genes encoding the innate immune Toll-like receptors (TLRs) are associated with inflammatory atherosclerosis. In hyperlipidemic mice, TLR2 and TLR4 have been reported to contribute to atherosclerosis progression. Human and mouse studies support a role for the oral pathogen Porphyromonas gingivalis in atherosclerosis, although the mechanisms by which this pathogen stimulates inflammatory atherosclerosis

Chie Hayashi; Andres G. Madrigal; Xinyan Liu; Takashi Ukai; Sulip Goswami; Cynthia V. Gudino; Frank C. Gibson; III; Caroline A. Genco

2010-01-01

287

Concept of Atherosclerosis Velocity: Is It a Better Measure of Cardiovascular Risk?  

PubMed Central

In most cases atherosclerosis is the underlying cause of vascular diseases, including heart disease and stroke. It is believed that endothelial injury is the earliest change in the artery wall and that this precedes the formation of lesions of atherosclerosis. Recent developments in the field of atherosclerosis have led to a renewed interest in the recognition of the parameter of time in the atherosclerosis process. We believe that the factors determining the time-dependent rate of atherosclerosis progression are important, and it is in this context that we wish to propose for the first time the term “atherosclerosis velocity”. In this review article, we summarize the existing evidence regarding atherosclerosis velocity and discuss the importance of this issue.

Kazemi-Bajestani, Seyyed Mohammad Reza; Ghayour-Mobarhan, Majid

2013-01-01

288

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

289

Deconstructing continuous flash suppression  

PubMed Central

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular “Mondrian” CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

Yang, Eunice; Blake, Randolph

2012-01-01

290

Phospholipase A2 enzymes and the risk of atherosclerosis.  

PubMed

Certain members of the phospholipase A(2) superfamily of enzymes have established causal involvement in atherosclerosis, thus at least two groups of this family of enzymes have been considered potential candidates for the prevention of cardiovascular events. Recently completed experimental animal studies, human biomarker data, vascular imaging studies, and genome-wide atherosclerosis studies provide the rationale for proceeding with clinical outcome trials directed at inhibition of secretory phospholipase A(2) and lipoprotein-associated phospholipase A(2). A clinical trial with the sPLA(2) inhibitor varespladib methyl was recently terminated, while clinical trials with the Lp-PLA(2) inhibitor darapladib are being conducted in coronary heart disease patients. This article reviews the available experimental animal and human trial evidence that serve as the basis for the development of these two classes of phospholipase A(2) inhibitors. PMID:22802388

Rosenson, Robert S; Hurt-Camejo, Eva

2012-07-15

291

Innate immunity and monocyte-macrophage activation in atherosclerosis  

PubMed Central

Innate inflammation is a hallmark of both experimental and human atherosclerosis. The predominant innate immune cell in the atherosclerotic plaque is the monocyte-macrophage. The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. Furthermore, the plaque microenvironment offers polarisation and activation signals which impact on phenotype. Microenvironmental signals are sensed through pattern recognition receptors, including toll-like and NOD-like receptors - the latter of which are components of the inflammasome - thus dictating macrophage behaviour and outcome in atherosclerosis. Recently cholesterol crystals and modified lipoproteins have been recognised as able to directly engage these pattern recognition receptors. The convergent role of such pathways in terms of macrophage activation is discussed in this review.

2011-01-01

292

HIV-related mechanisms in atherosclerosis and cardiovascular diseases.  

PubMed

HIV-infected patients have a significantly higher risk of developing cardiovascular events during the progression of HIV disease. Atherosclerosis, myocardial infarction, cerebrovascular injury, pulmonary hypertension and thrombosis are consistently described in both combined antiretroviral therapy (cART)-treated and naive HIV-positive patients as major clinical complications. Recent studies indicate that the pathogenesis of cardiovascular lesions in HIV-positive patients is related to direct and indirect effects of HIV infection on vessel structures, independently of traditional risk factors. HIV infection strongly interferes with the biology of several cellular targets such as macrophage and endothelial cells. Moreover, HIV induces a profound derangement of lipid metabolism and inflammatory cytokine networks that are directly involved in atherogenesis and progressive impairment of the cardiovascular system.In this review, we discuss these major HIV-related mechanisms able to promote atherosclerosis and cardiovascular diseases in HIV-positive patients. PMID:23656915

Gibellini, Davide; Borderi, Marco; Clò, Alberto; Morini, Silvia; Miserocchi, Anna; Bon, Isabella; Ponti, Cristina; Re, Maria Carla

2013-11-01

293

Natural killer T cells in lipoprotein metabolism and atherosclerosis.  

PubMed

Cells of both the innate and adaptive immune system participate in the development of atherosclerosis, a chronic inflammatory disorder of medium and large arteries. Natural killer T (NKT) cells express surface markers characteristic of natural killer cells and conventional T cells and bridge the innate and adaptive immune systems. The development and activation of NKT cells is dependent upon CD1d, a MHC-class I-type molecule that presents lipids, especially glycolipids to the T cell receptors on NKT cells. There are two classes of NKT cells; invariant NKT cells that express a semi-invariant T cell receptor and variant NKT cells. This review summarises studies in murine models in which the effect of the activation, overexpression or deletion of NKT cells or only invariant NKT cells on atherosclerosis has been examined. PMID:21946866

Getz, G S; Vanderlaan, P A; Reardon, C A

2011-09-22

294

Imaging of coronary atherosclerosis and identification of the vulnerable plaque  

PubMed Central

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

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

2003-01-01

295

Local proliferation dominates lesional macrophage accumulation in atherosclerosis.  

PubMed

During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall. The observation that circulating monocytes give rise to lesional macrophages has reinforced the concept that monocyte infiltration dictates macrophage buildup. Recent work has indicated, however, that macrophage accumulation does not depend on monocyte recruitment in some inflammatory contexts. We therefore revisited the mechanism underlying macrophage accumulation in atherosclerosis. In murine atherosclerotic lesions, we found that macrophages turn over rapidly, after 4 weeks. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. The microenvironment orchestrates macrophage proliferation through the involvement of scavenger receptor A (SR-A). Our study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease. PMID:23933982

Robbins, Clinton S; Hilgendorf, Ingo; Weber, Georg F; Theurl, Igor; Iwamoto, Yoshiko; Figueiredo, Jose-Luiz; Gorbatov, Rostic; Sukhova, Galina K; Gerhardt, Louisa M S; Smyth, David; Zavitz, Caleb C J; Shikatani, Eric A; Parsons, Michael; van Rooijen, Nico; Lin, Herbert Y; Husain, Mansoor; Libby, Peter; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K

2013-08-11

296

Association between atherosclerosis and osteoporosis, the role of vitamin D  

PubMed Central

The latest data support the correlation of atherosclerosis and osteoporosis, indicating the parallel progression of two tissue destruction processes with increased fatal and non-fatal coronary events, as well as higher fracture risk. Vitamin D inadequacy associated with low bone mineral density increases fall and fracture risk, leads to secondary hyperparathyroidism, calcifies coronary arteries and significantly increases cardiovascular disease. Randomized clinical trial evidence related to extraskeletal vitamin D outcomes was limited and generally uninformative. A recent recommendation on vitamin D dietary requirements for bone health is 600 IU/d for ages 1-70 years and 800 IU/d for 71 years and older, corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/l). Further large randomized controlled trials are needed to reassess laboratory ranges for 25-hydroxyvitamin D in both diseases, in order to avoid under- and over-treatment problems, and completely clarify the relationship between atherosclerosis and osteoporosis.

Stojanovic, Olivera Ilic; Lazovic, Milica; Lazovic, Marko; Vuceljic, Marina

2011-01-01

297

Impact of Ezetimibe on Atherosclerosis: Is the Jury Still Out?  

PubMed Central

Ezetimibe is a new lipid-lowering agent that inhibits intestinal absorption of dietary cholesterol. It substantially lowers low-density lipoprotein cholesterol levels when used alone or in combination with statins. However, its effect on cardiovascular mortality remains unknown. We reviewed peer-reviewed published literature on the effect of ezetimibe on different phases of atherosclerosis. MEDLINE, EMBASE, BIOSIS, and other Web of Knowledge databases were searched for relevant abstracts and articles published in the English language that compared ezetimibe and statins as modulators of atherosclerosis. On the basis of the available evidence, ezetimibe appears to reduce inflammation when used in combination with statins, but its effect on endothelial function is mixed and less clear. The effect of ezetimibe on coronary disease progression or prevention of cardiovascular events is currently unknown. Use of ezetimibe as a second- or third-line agent to achieve low-density lipoprotein cholesterol treatment goals seems appropriate on the basis of the available evidence.

Al Badarin, Firas J.; Kullo, Iftikhar J.; Kopecky, Stephen L.; Thomas, Randal J.

2009-01-01

298

Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis.  

PubMed

Diabetes is a major risk factor for atherosclerosis. Although atherosclerosis is initiated by deposition of cholesterol-rich lipoproteins in the artery wall, the entry of inflammatory leukocytes into lesions fuels disease progression and impairs resolution. We show that diabetic mice have increased numbers of circulating neutrophils and Ly6-C(hi) monocytes, reflecting hyperglycemia-induced proliferation and expansion of bone marrow myeloid progenitors and release of monocytes into the circulation. Increased neutrophil production of S100A8/S100A9, and its subsequent interaction with the receptor for advanced glycation end products on common myeloid progenitor cells, leads to enhanced myelopoiesis. Treatment of hyperglycemia reduces monocytosis, entry of monocytes into atherosclerotic lesions, and promotes regression. In patients with type 1 diabetes, plasma S100A8/S100A9 levels correlate with leukocyte counts and coronary artery disease. Thus, hyperglycemia drives myelopoiesis and promotes atherogenesis in diabetes. PMID:23663738

Nagareddy, Prabhakara R; Murphy, Andrew J; Stirzaker, Roslynn A; Hu, Yunying; Yu, Shiquing; Miller, Rachel G; Ramkhelawon, Bhama; Distel, Emilie; Westerterp, Marit; Huang, Li-Shin; Schmidt, Ann Marie; Orchard, Trevor J; Fisher, Edward A; Tall, Alan R; Goldberg, Ira J

2013-05-01

299

Coronary Atherosclerosis and Cardiovascular Risk in Masters Male Marathon Runners  

Microsoft Academic Search

Background:  Regular physical exercise is recommended to reduce cardiovascular mortality. And yet, atherosclerosis is the main cause of exercise-associated death in persons beyond age 35. The need for risk stratification in marathon runners is under discussion. The predictive value of modern imaging- and non-imaging-based markers of risk that can be used for risk stratification in masters endurance athletes still deserves exploration.Methods:  Male

Stefan Möhlenkamp; Axel Schmermund; Knut Kröger; Gert Kerkhoff; Martina Bröcker-Preuss; Volker Adams; Martin Hensel; David Kiefer; Nils Lehmann; Susanne Moebus; Kirsten Leineweber; Sigrid Elsenbruch; Jörg Barkhausen; Martin Halle; Rainer Hambrecht; Johannes Siegrist; Klaus Mann; Thomas Budde; Karl-Heinz Jöckel; Raimund Erbel

2006-01-01

300

Aortic Atherosclerosis in Free-ranging Howler Monkeys (Alouatta caraya  

Microsoft Academic Search

NATURALLY occurring atherosclerosis in non-human primates has been described in isolated instances1, but few observations of this disease in free-ranging monkeys have been reported2. A recent field trip to South America afforded the opportunity to examine 314 howler monkeys (Alouatta caraya) at Bella Vista, Corrientes, Argentina. A complete post-mortem examination was performed on practically all animals. The heart, great arteries,

M. R. Malinow; C. A. Maruffo

1965-01-01

301

A Review of Atherosclerosis and Mathematical Transport Models  

Microsoft Academic Search

\\u000a The mechanisms and definitive predictive components involved within the clinical initiation and formation of atherosclerosis\\u000a remain elusive as of yet. Over the years, established fluid and mass transport theories and experimentally agreed upon vasoactive\\u000a agents have contributed towards a boom of predictive mathematical models concerning atherogenesis. This paper aims to elucidate\\u000a currently utilized theories available regarding initiation of atherosclerotic proliferation

B. Keller; F. Clubb Jr; G. Dubini

302

Chemokine receptor CCR5: from AIDS to atherosclerosis  

PubMed Central

There is increasing recognition of an important contribution of chemokines and their receptors in the pathology of atherosclerosis and related cardiovascular disease. The chemokine receptor CCR5 was initially known for its role as a co-receptor for HIV infection of macrophages and is the target of the recently approved CCR5 antagonist maraviroc. However, evidence is now emerging supporting a role for CCR5 and its ligands CCL3 (MIP-1?), CCL4 (MIP-1?) and CCL5 (RANTES) in the initiation and progression of atherosclerosis. Specifically, the CCR5 deletion polymorphism CCR5delta32, which confers resistance to HIV infection, has been associated with a reduced risk of cardiovascular disease and both CCR5 antagonism and gene deletion reduce atherosclerosis in mouse models of the disease. Antagonism of CCL5 has also been shown to reduce atherosclerotic burden in these animal models. Crucially, CCR5 and its ligands CCL3, CCL4 and CCL5 have been identified in human and mouse vasculature and have been detected in human atherosclerotic plaque. Not unexpectedly, CC chemokines have also been linked to saphenous vein graft disease, which shares similarity to native vessel atherosclerosis. Distinct roles for chemokine–receptor systems in atherogenesis have been proposed, with CCR5 likely to be critical in recruitment of monocytes to developing plaques. With an increased burden of cardiovascular disease observed in HIV-infected individuals, the potential cardiovascular-protective effects of drugs that target the CCR5 receptor warrant greater attention. The availability of clinically validated antagonists such as maraviroc currently provides an advantage for targeting of CCR5 over other chemokine receptors.

Jones, KL; Maguire, JJ; Davenport, AP

2011-01-01

303

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].

Pakozdi, Angela; Besenyei, Timea; Paragh, Gyorgy; Koch, Alisa E.; Szekanecz, Zoltan

2010-01-01

304

Relationship of the apolipoprotein E polymorphism with carotid artery atherosclerosis.  

PubMed Central

From the cohort taking part in the Atherosclerosis Risk in Communities (ARIC) study, a multicenter investigation of atherosclerosis and its sequelae in women and men ages 45-64 years, a sample of 145 subjects with significant carotid artery atherosclerosis but without clinically recognized coronary heart disease was identified along with 224 group-matched control subjects. The aim of this paper is to measure the association of the apolipoprotein (apo) E polymorphism with the prevalence of significant carotid artery atherosclerotic disease (CAAD) after considering the contribution of established risk factor variables. The first model used a stepwise selection procedure to define a group of significant physical and lifestyle characteristics and a group of significant plasma lipid, lipoprotein, and apolipoprotein variables that were predictive of CAAD status in this sample. Those variables selected included age (years), body mass index (BMI; kg/m2), consumption of cigarettes (CigYears; number of cigarettes/d x the number of smoking years), hypertension status, high-density lipoprotein (HDL)-cholesterol (mg/dl), total cholesterol (mg/dl), and Lp[a] (micrograms/ml). The second model was built by forcing into the equation an a priori set of demographic, anthropometric, and lipoprotein variables, which were age, BMI, CigYears, hypertensive status, LDL-cholesterol, and HDL-cholesterol. In both models, the apo E genotype epsilon 2/3 was related to CAAD status. For both models, the estimated odds ratio of being a CAAD case associated with the apo E genotype epsilon 2/3 was > 2:1. The mechanism of the observed association between the epsilon 2/3 genotype and carotid atherosclerosis is unknown, but it is likely due to the known effects of the E2 isoform in causing delayed clearance of triglyceride-rich lipoproteins.

de Andrade, M; Thandi, I; Brown, S; Gotto, A; Patsch, W; Boerwinkle, E

1995-01-01

305

P2 receptors in atherosclerosis and postangioplasty restenosis  

Microsoft Academic Search

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

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

2007-01-01

306

Nuclear Transport Modulation Reduces Hypercholesterolemia, Atherosclerosis, and Fatty Liver  

PubMed Central

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

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

2013-01-01

307

Numerical and analytical study of an atherosclerosis inflammatory disease model.  

PubMed

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

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

2013-05-30

308

Particulate air pollution, systemic oxidative stress, inflammation, and atherosclerosis  

Microsoft Academic Search

Air pollution has been associated with significant adverse health effects leading to increased overall morbidity and mortality\\u000a of worldwide significance. Epidemiological studies have shown that the largest portion of air pollution-related mortality\\u000a is due to cardiovascular diseases, predominantly those of ischemic nature. Human studies suggest an association with atherosclerosis\\u000a and increasing experimental animal data support that this association is likely

Jesus A. Araujo

2011-01-01

309

Inflammatory and oxidative markers in atherosclerosis: Relationship to outcome  

Microsoft Academic Search

Inflammation and oxidative processes are key components of atherosclerosis, from fatty streak formation to plaque rupture\\u000a and thrombosis. Recent basic and clinical studies have identified a number of inflammatory and oxidative processes that appear\\u000a to play a direct role in atherothrombosis and identify potentially clinically useful markers of inflammation and oxidative\\u000a stress. In this review, we highlight recent results on

Mehdi H. Shishehbor; Stanley L. Hazen

2004-01-01

310

Chemokine-like functions of MIF in atherosclerosis  

Microsoft Academic Search

The cytokine macrophage migration inhibitory factor (MIF) is a unique pro-inflammatory regulator of many acute and chronic\\u000a inflammatory diseases. In the pathogenesis of atherosclerosis, chronic inflammation of the arterial wall characterized by\\u000a chemokine-mediated influx of leukocytes plays a central role. The contribution of MIF to atherosclerotic vascular disease\\u000a has come into focus of many studies in recent years. MIF is

Andreas Schober; Jürgen Bernhagen; Christian Weber

2008-01-01

311

[Correction of disordered cerebral blood flow autoregulation in atherosclerosis].  

PubMed

The work deals with studying the parameters of autoregulation of the cerebral blood flow in a total of 127 patients subdivided into four groups. Clinical Group I consisted of thirty 45-to-70-year-old male patients (mean age 55.13 +/- 6.44 years) presenting with no signs of systemic atherosclerosis (CAD, chronic arterial insufficiency of the lower extremities, cerebrovascular insufficiency) or any other chronic diseases (chronic cardiac, pulmonary or renal insufficiency, chronic hepatitis, etc.). Clinical Group II comprised 32 patients diagnosed as having varying-degree chronic arterial insufficiency on the background of atherosclerosis obliterans of the lower-limb arteries (average age 57.46 +/- 5.15 years). Clinical Group III was composed of 30 patients presenting with different degrees of chronic cerebral ischaemia and having haemodynamically significant unilateral atherosclerotic lesions of the internal carotid artery (mean age 55.39 +/- 6.25 years), with the Control Group enrolling thirty-five 20-to-25-year-old volunteers. The findings of the work showed that the patients with atherosclerosis had significant impairments of the cerebral blood flow autoregulation, whose type and degree appeared to depend upon localization of the lesion. In the patients with peripheral atherosclerosis, a 10-day therapeutic course of intravenous administration of alpha-lipoic acid (Berlithion) at a dose of 600 mg daily could be used to correct disordered autoregulation of the cerebral vessels and may be considered from the position of preoperative preparation of such patients for reconstructive vascular interventions on the aorta and lower-limb arteries. Efficacy of alpha-lipoic acid (Berlithion) on the alterations in the cerebral blood flow autoregulation in patients presenting with haemodynamic stenosis of the internal carotid artery is insignificant, in connection with which such patients require surgical restoration of the patency of the major cerebral arteries. PMID:20092178

Fedin, A I; Kuznetsov, M R; Beresten', N F; Kuznetsova, V F; Kholopova, E A; Ibragimov, T M; Tugdumov, B V; Dubrovin, E E

2009-01-01

312

Chemokine receptor CCR5: from AIDS to atherosclerosis.  

PubMed

There is increasing recognition of an important contribution of chemokines and their receptors in the pathology of atherosclerosis and related cardiovascular disease. The chemokine receptor CCR5 was initially known for its role as a co-receptor for HIV infection of macrophages and is the target of the recently approved CCR5 antagonist maraviroc. However, evidence is now emerging supporting a role for CCR5 and its ligands CCL3 (MIP-1?), CCL4 (MIP-1?) and CCL5 (RANTES) in the initiation and progression of atherosclerosis. Specifically, the CCR5 deletion polymorphism CCR5delta32, which confers resistance to HIV infection, has been associated with a reduced risk of cardiovascular disease and both CCR5 antagonism and gene deletion reduce atherosclerosis in mouse models of the disease. Antagonism of CCL5 has also been shown to reduce atherosclerotic burden in these animal models. Crucially, CCR5 and its ligands CCL3, CCL4 and CCL5 have been identified in human and mouse vasculature and have been detected in human atherosclerotic plaque. Not unexpectedly, CC chemokines have also been linked to saphenous vein graft disease, which shares similarity to native vessel atherosclerosis. Distinct roles for chemokine-receptor systems in atherogenesis have been proposed, with CCR5 likely to be critical in recruitment of monocytes to developing plaques. With an increased burden of cardiovascular disease observed in HIV-infected individuals, the potential cardiovascular-protective effects of drugs that target the CCR5 receptor warrant greater attention. The availability of clinically validated antagonists such as maraviroc currently provides an advantage for targeting of CCR5 over other chemokine receptors. PMID:21133894

Jones, K L; Maguire, J J; Davenport, A P

2011-04-01

313

Review: The physiological and computational approaches for atherosclerosis treatment.  

PubMed

The cardiovascular disease has long been an issue that causes severe loss in population, especially those conditions associated with arterial malfunction, being attributable to atherosclerosis and subsequent thrombotic formation. This article reviews the physiological mechanisms that underline the transition from plaque formation in atherosclerotic process to platelet aggregation and eventually thrombosis. The physiological and computational approaches, such as percutaneous coronary intervention and stent design modeling, to detect, evaluate and mitigate this malicious progression were also discussed. PMID:23103138

Wang, Wuchen; Lee, Yugyung; Lee, Chi H

2012-10-23

314

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

315

The AGE/RAGE axis in diabetes-accelerated atherosclerosis.  

PubMed

1. There is increasing evidence that advanced glycation end-products (AGEs) and their interaction with the receptor RAGE play a pivotal role in atherosclerosis, in particular in the setting of diabetes. 2. Previous studies have shown that inhibition of AGE accumulation and RAGE expression in diabetes by either reduction of the formation of AGEs or cross-link breakers was associated with reduced atherosclerosis and renal disease. Advanced glycation end-products bind to RAGE, thereby leading to activation of a range of inflammatory and fibrotic pathways causing tissue injury. Different splice variants of RAGE exist, including a soluble form that lacks the intracellular domain and fails to induce signal transduction. Therapeutic approaches using soluble RAGE as a decoy binding protein for circulating AGE have been effective in preventing externally induced arterial injury and atherosclerosis in the absence and presence of diabetes. 3. In order to delineate the role of RAGE in vascular disease in more detail, it was necessary to create RAGE(-/-) mice, as well as transgenic mice overexpressing RAGE in endothelial cells. It was shown that RAGE overexpression was associated with increased vascular injury, nephropathy and retinopathy. 4. In contrast, RAGE deletion was associated with partial vascular protection, such as reduced neointima formation after arterial denudation, as well as protection from diabetic nephropathy. The present review summarizes the evidence for RAGE being a pro-inflammatory and pro-fibrotic receptor. 5. Further studies are needed to delineate the effect of RAGE deletion and overexpression in diabetic macrovascular disease. Based on these findings, RAGE could be a potential therapeutic target in combating inflammatory vascular diseases, including diabetes-associated atherosclerosis. PMID:18290873

Jandeleit-Dahm, Karin; Watson, Anna; Soro-Paavonen, Aino

2008-03-01

316

The improper use of the term "normal" in atherosclerosis research.  

PubMed

The improper use of the term "normal" was frequently detected in the available literature, in studies dealing with coronary artery anatomy, pathology and angiography, as well as in epidemiological investigations. Many examples are presented which try to demonstrate that without a clear understanding of the normal, it is a very difficult task to explore the abnormal during coronary atherogenesis and the successive stages which form the natural history of coronary atherosclerosis. PMID:3055240

Velican, C; St?nescu, C

317

Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease  

PubMed Central

Atherosclerosis is the underlying reason for nearly all causes of coronary artery disease and peripheral arterial disease and many cases of stroke. Atherosclerosis is a systemic inflammatory process characterised by the accumulation of lipids and macrophages/lymphocytes within the intima of large arteries. The deposition of these blood borne materials and the subsequent thickening of the wall often significantly compromise the residual lumen leading to ischaemic events distal to the arterial stenosis. However, these initial fatty streak lesions may also evolve into vulnerable plaques susceptible to rupture or erosion. Plaque disruption initiates both platelet adhesion and aggregation on the exposed vascular surface and the activation of the clotting cascade leading to the so-called atherothrombotic process. Yet, platelets have also been shown to be transporters of regulatory molecules (micro-RNA), to drive the inflammatory response and mediate atherosclerosis progression. Here we discuss our current understanding of the pathophysiological mechanisms involved in atherogenesis – from fatty streaks to complex and vulnerable atheromas – and highlight the molecular machinery used by platelets to regulate the atherogenic process, thrombosis and its clinical implications.

Padro, Teresa; Vilahur, Gemma

2012-01-01

318

Serum VEGF--as a prognostic factor of atherosclerosis.  

PubMed

Vascular endothelial growth factor (VEGF) has been noted in the pathogenesis of atherosclerosis. To examine the usefulness of the serum concentration of VEGF as an index of atherosclerosis, we analyzed the serum VEGF concentrations in 443 adults who underwent a medical checkup. The mean serum VEGF concentration of men (229+/-147 pg/ml) was significantly higher than that of women (182+/-112 pg/ml). The platelet count showed a slight correlation with the serum VEGF concentration in both genders (men R=0.287, women R=0.296), corresponding with the results of experiments that platelets are the major source of VEGF in circulating peripheral blood. In men, the serum VEGF concentrations correlated with platelet counts, body fat percentages, leukocyte counts, and HDL-cholesterol concentrations (negative correlation). In the multiple regression analysis performed for men's serum VEGF concentrations, the decision coefficient (R2) was maximized (R2=0.173) when the leukocyte count, the body fat percentage, and the HDL-cholesterol concentration were taken into account besides the platelet count. Male smokers' serum VEGF concentrations were higher than non-smokers'. Smoking in men significantly affected the sex difference in the serum VEGF concentration, leukocyte count, and HDL-cholesterol concentration. We concluded that the serum VEGF concentration might be closely related to atherosclerosis accelerating factor, especially in men. PMID:17141247

Kimura, Kuriko; Hashiguchi, Teruto; Deguchi, Takahisa; Horinouchi, Shuji; Uto, Tadashi; Oku, Hiroko; Setoyama, Shiro; Maruyama, Ikuro; Osame, Mitsuhiro; Arimura, Kimiyoshi

2006-12-01

319

Mechanisms and therapy of atherosclerosis and its clinical complications.  

PubMed

In 1913, exactly 100 years ago, Nikolai Nikolaevich Anichkov (1885-1964) and Semen Sergeevich Chalatov (1884-1951) discovered in St. Petersburg, Russia, that atherosclerosis of large arteries is critically dependent on cholesterol. The inflammatory nature of atherosclerosis was first observed and suggested by Rudolf Virchow in 1856. Today, we have orally active drugs at our disposition that not only lower cholesterol levels but also interfere with vascular inflammation and atherogenesis. The disease process is multifactorial and its development is accelerated by modifiable and given risk factors such as cigarette smoking, dyslipidemia, arterial hypertension, diabetes, obesity, physical inactivity, estrogen deficiency, chronic renal disease, genetic predisposition, and the physiological aging process, among others. The present issue of Current Opinion in Pharmacology features a collection of articles by clinicians and scientists-many of whom are world authorities in their field-on mechanisms, preventive measures, clinical complications, and treatment of coronary artery disease. This monograph provides a '2013 update' on the pathogenesis, prevention, and therapy of atherosclerosis. PMID:23721738

Barton, Matthias

2013-05-28

320

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.

2007-03-01

321

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

322

Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease.  

PubMed

Atherosclerosis is the underlying reason for nearly all causes of coronary artery disease and peripheral arterial disease and many cases of stroke. Atherosclerosis is a systemic inflammatory process characterised by the accumulation of lipids and macrophages/lymphocytes within the intima of large arteries. The deposition of these blood borne materials and the subsequent thickening of the wall often significantly compromise the residual lumen leading to ischaemic events distal to the arterial stenosis. However, these initial fatty streak lesions may also evolve into vulnerable plaques susceptible to rupture or erosion. Plaque disruption initiates both platelet adhesion and aggregation on the exposed vascular surface and the activation of the clotting cascade leading to the so-called atherothrombotic process. Yet, platelets have also been shown to be transporters of regulatory molecules (micro-RNA), to drive the inflammatory response and mediate atherosclerosis progression. Here we discuss our current understanding of the pathophysiological mechanisms involved in atherogenesis - from fatty streaks to complex and vulnerable atheromas - and highlight the molecular machinery used by platelets to regulate the atherogenic process, thrombosis and its clinical implications. PMID:24062891

Badimon, Lina; Padró, Teresa; Vilahur, Gemma

2012-04-01

323

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

2013-03-13

324

DNA modifications in atherosclerosis: From the past to the future.  

PubMed

The role of DNA damage in the pathogenesis of atherosclerosis has been extensively investigated in recent decades. There is now clear that oxidative stress is an important inducer of both DNA damage and telomere attrition which, in turn, can gives rise to genome instability and vascular senescence. This review discusses the role of the DNA damage response, including the key DNA repair pathways (base excision repair, nucleotide excision repair, homologous recombination and non-homologous end joining), deregulated cell cycle and apoptosis in atherosclerosis. We also highlight emerging evidence suggesting that epigenetic changes (DNA methylation and microRNA-mediated mechanisms), not associated with alterations in DNA sequences, may play a critical role in the regulation of the DNA damage response. Nevertheless, further investigation is still required to better understand the complexity of DNA repair and DNA damage response in atherosclerosis, making this topic an exciting and promising field for future investigation. Unraveling these molecular mechanisms provide the rationale for the development of novel efficient therapies to combat the vascular aging process. PMID:24075745

Borghini, Andrea; Cervelli, Tiziana; Galli, Alvaro; Andreassi, Maria Grazia

2013-07-27

325

[To question of etiology and pathogenesis of atherosclerosis].  

PubMed

On the ground own researches and researches of other authors etiology and pathogenesis of atherosclerosis are proved and refuted existing concept about leading role of disturbance of lipid exchange and atherogenicity of lipoproteins of low and very low density. Established basic etiological factors of damage intima of artery and reason of penetration of lipoproteins in intima after her damage. Is determined that development and progression of atherosclerosis do not depend also from quantitative content of lipoproteins of low density in blood and from normalization of them under influence of drugs. According to our researches atherosclerosis is the polyetiological chronic disease basis of pathogeny which is infringement of blood supply (chronic microcirculatory insufficiency) in arterial wall causing damage of it, and in first place, damage of intima with her most vulnerable microcirculation; inflammation intima hence influence of endogenous and exogenous factors; destruction of antiaggregatic and fibrinolytic properties of intima in places of her damage; formation atherosclerotic plaque with level-by-level imposing of lipoproteins in result of cyclic process of restoration or balance between coagulation and anticoagulation of blood systems. PMID:23951908

326

Effects of Fluvastatin on Coronary Atherosclerosis in Patients With Mild to Moderate Cholesterol Elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS])  

Microsoft Academic Search

Despite the potential for reduced morbidity and mortality, aggressive intervention against mild to moderate hypercholesterolemia in patients with coronary heart disease (CHD) remains controversial and infrequently practiced. Eligible patients in the 2.5-year Lipoprotein and Coronary Atherosclerosis Study were men and women aged 35 to 75 years with angiographic CHD and mean low-density lipoprotein (LDL) cholesterol of 115 to 190 mg\\/dl

James J. Ferguson; Antonio M. Gotto

1997-01-01

327

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

Microsoft Academic Search

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

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

2011-01-01

328

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

Microsoft Academic Search

\\u000a Atherosclerosis, a pathology affecting arterial blood vessels, is one of most common diseases of the developed countries.\\u000a We present studies on the increased atherosclerosis risk using an agent based model of atherogenesis that has been previously\\u000a validated using clinical data. It is well known that the major risk in atherosclerosis is the persistent high level of low\\u000a density lipoprotein (LDL)

Francesco Pappalardo; Alessandro Cincotti; Alfredo Motta; Marzio Pennisi

2009-01-01

329

CD1d-dependent Activation of NKT Cells Aggravates Atherosclerosis  

Microsoft Academic Search

Adaptive and innate immunity have been implicated in the pathogenesis of atherosclerosis. Given their abundance in the lesion, lipids might be targets of the atherosclerosis-associated immune response. Natural killer T (NKT) cells can recognize lipid antigens presented by CD1 molecules. We have explored the role of CD1d-restricted NKT cells in atherosclerosis by using apolipoprotein E-deficient (apoE ? \\/ ? )

Emmanuel Tupin; Antonino Nicoletti; Rima Elhage; Mats Rudling; Hans-Gustaf Ljunggren; Göran K. Hansson; Gabrielle Paulsson Berne

330

Chlamydia pneumoniae Infection Does Not Induce or Modify Atherosclerosis in Mice  

Microsoft Academic Search

Background—Seroepidemiological studies have linked Chlamydia pneumoniae(CP) to coronary heart disease, and recent experimental studies suggest that it may accelerate or even induce atherosclerosis. We therefore evaluated the effect of CP infection on atherosclerosis in atherosclerosis-prone apolipoprotein E- knockout (apoE-KO) and wild-type C57BL\\/6J mice. Methods and Results—Six- to 8-week-old female mice were infected intranasally with live CP and then fed a

Giuseppina Caligiuri; Martin Rottenberg; Antonino Nicoletti; Hans Wigzell; Göran K. Hansson

2010-01-01

331

Suppression Workshop Summary.  

National Technical Information Service (NTIS)

A workshop on the Chemical Suppression of Rocket Afterburning and of Gun Muzzle Flash was held at the Ballistic Research Laboratory on 11 and 12 June 1986. It brought together scientists representing six countries to share their collective fundamental und...

J. M. Heimerl

1987-01-01

332

Parasitic Suppressing Circuit.  

National Technical Information Service (NTIS)

A circuit for suppressing parasitic oscillations across an inductor operating in a resonant mode is described. The circuit includes a switch means and resistive means connected serially across the inductor. A unidirectional resistive-capacitive network is...

F. L. Raposa J. T. Fowler

1972-01-01

333

Parasitic Suppressing Circuit.  

National Technical Information Service (NTIS)

A circuit for suppressing parasitic oscillations across an inductor operating in a resonant mode is described. The circuit includes a switch means and resistive means connected serially across the inductor. A unidirectional resistive-capacitive network is...

J. T. Fowler F. L. Raposa

1973-01-01

334

Eptifibatide does not suppress the increase of inflammatory markers in patients with non-ST-segment elevation acute coronary syndrome  

Microsoft Academic Search

Background Platelets are involved in inflammatory reactions which play an important role in the development of atherosclerosis and its\\u000a acute complications. The objective of this study was to test the ability of glycoprotein (GP) IIb-IIIa antagonist eptifibatide\\u000a to suppress the increase of inflammatory markers in non-ST-segment elevation acute coronary syndrome (ACS). Methods Twenty-five patients with unstable angina and non-ST-segment elevation

Alexey A. Mazaev; Yaroslav A. Naimushin; Valery P. Masenko; Mikhail Y. Ruda; Alexey V. Mazurov

2009-01-01

335

Angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis.  

PubMed

The endothelium plays a central role in the maintenance of vascular homeostasis. One of the main effectors of endothelial dysfunction is ANG II, and pharmacological approaches to limit ANG II bioactivity remain the cornerstone of cardiovascular therapeutics. Angiotensin converting enzyme-2 (ACE2) has been identified as a critical negative modulator of ANG II bioactivity, counterbalancing the effects of ACE in determining net tissue ANG II levels; however, the role of ACE2 in the vasculature remains unknown. In the present study, we hypothesized that ACE2 is a novel target to limit endothelial dysfunction and atherosclerosis. To this aim, we performed in vitro gain and loss of function experiments in endothelial cells and evaluated in vivo angiogenesis and atherosclerosis in apolipoprotein E-knockout mice treated with AdACE2. ACE2-deficient mice exhibited impaired endothelium-dependent relaxation. Overexpression of ACE2 in human endothelial cells stimulated endothelial cell migration and tube formation, and limited monocyte and cellular adhesion molecule expression; effects that were reversed in ACE2 gene silenced and endothelial cells isolated from ACE2-deficient animals. ACE2 attenuated ANG II-induced reactive oxygen species production in part through decreasing the expression of p22phox. The effects of ACE2 on endothelial activation were attenuated by pharmacological blockade of ANG-(1-7) with A779. ACE2 promoted capillary formation and neovessel maturation in vivo and reduced atherosclerosis in apolipoprotein E-knockout mice These data indicate that ACE2, in an ANG-(1-7)-dependent fashion, functions to improve endothelial homeostasis via a mechanism that may involve attenuation of NADPHox-induced reactive oxygen species production. ACE2-based treatment approaches may be a novel approach to limit aberrant vascular responses and atherothrombosis. PMID:18660448

Lovren, Fina; Pan, Yi; Quan, Adrian; Teoh, Hwee; Wang, Guilin; Shukla, Praphulla C; Levitt, Kevin S; Oudit, Gavin Y; Al-Omran, Mohammed; Stewart, Duncan J; Slutsky, Arthur S; Peterson, Mark D; Backx, Peter H; Penninger, Josef M; Verma, Subodh

2008-07-25

336

The Role of Phospholipid Oxidation Products in Atherosclerosis  

PubMed Central

There is increasing clinical evidence that phospholipid oxidation products (Ox-PL) play a role in atherosclerosis. This review focuses on the mechanisms by which Ox-PL interact with endothelial cells, monocyte/macrophages, platelets, smooth muscle cells and HDL to promote atherogenesis. In the last few years major progress has been made in identifying these mechanisms. It has been recognized that Ox-PL promote phenotypic changes in these cell types that have long term consequences for the vessel wall. Individual Ox-PL responsible for specific cellular effects has been identified. A model of the configuration of bioactive truncated Ox-PL within membranes has been developed that demonstrates that the oxidized fatty acid moiety protrudes into the aqueous phase, rendering it accessible for receptor recognition. Receptors and signaling pathways for individual Ox-PL species are now determined and receptor independent signaling pathways identified. The effects of Ox-PL are mediated both by gene regulation and transcription independent processes. It has now become apparent that Ox-PL affects multiple genes and pathways some of which are pro-atherogenic and some are protective. However, at concentrations that are likely present in the vessel wall in atherosclerotic lesions, the effects promote atherogenesis. There have also been new insights on enzymes that metabolize Ox-PL and the significance of these enzymes for atherosclerosis. With the knowledge we now have on the regulation and effects of Ox-PL in different vascular cell types, it should be possible to design experiments to test the role of specific Ox-PL on the development of atherosclerosis.

Lee, Sangderk; Birukov, Konstantin G.; Romanoski, Casey E.; Springstead, James R.; Lusis, Aldons J.; Berliner, Judith A.

2012-01-01

337

Risk Factors for Subclinical Atherosclerosis in Diabetic and Obese Children  

PubMed Central

Background. Increased carotid intima-media thickness (cIMT) is considered a marker of early-onset atherosclerosis and it seems to predict cardiovascular events both in obese and diabetic subjects. We aimed to evaluate early signs of atherosclerosis and investigate for predisposing factors in children and adolescents affected by type 1 diabetes (T1DM) or obesity, comparing them with healthy controls. Methods. Out of 71 enrolled subjects (mean age 12.8 ± 2.3 years), 26 had T1DM and 24 were obese, while 21 age- and sex-matched subjects acted as controls. cIMT was measured using standardized methods. Serum glucose, insulin, cholesterol, triglycerides and C-reactive protein levels were evaluated. An oral glucose tolerance test (OGTT) was performed in obese subjects. Results. Diabetic and obese individuals showed higher cIMT mean values than healthy controls (p<0.005). cIMT of the three examined segments correlated positively with fasting glucose levels and negatively with units of insulin/kg/day administered in T1DM individuals. A positive correlation between insulin levels (basal and after oral glucose load) and cIMT of common, internal and external carotid artery was found in obese subjects (p<0.03). High density cholesterol levels represented a protective factor for cIMT in this latter group of the study population. Conclusions. Our findings show that cIMT correlates with high insulin levels (a sign of insulin resistance) in obese patients and with high fasting glucose levels (a sign of relative insulin deficiency) in T1DM subjects, confirming the need of reducing hyperinsulinism and monitoring blood glucose levels in these subjects to prevent atherosclerosis.

Faienza, Maria Felicia; Acquafredda, Angelo; Tesse, Riccardina; Luce, Vincenza; Ventura, Annamaria; Maggialetti, Nicola; Monteduro, Mariantonietta; Giordano, Paola; Cavallo, Luciano

2013-01-01

338

In vitro experimental photodynamic diagnosis of artery atherosclerosis  

NASA Astrophysics Data System (ADS)

Background: Although there are several methods for atherosclerosis detection available, none of them seems to be accurate enough to identify the vulnerable atheroscleroitc plaque. Photodynamic diagnosis (PDD) and therapy (PDT) -- a new method evaluated for neoplasms treatment is a modern approach to detecting and treating atherosclerosis. Aim: The purpose of this study was to assess in vitro the capability of PDD with use of chlorin e6 to recognize atherosclerotic plaque and its usefulness as a feedback system for photoangioplasty treatment. Methods: 30 specimens of human aorta. The samples were soaked with chlorin e6 and then washed out. The luminescence spectra were then collected. All samples were examined with light microscopy. Results: Tissue fluorescence is seen as green light. We noted a very strong red fluorescence of chlorin e6 originating from lipid reach plaque. We established a quantitative factor which would be the ratio R of chlorin e6 red intensity in its 660 nm maximum compared to the area of green luminescence centered at 515 nm. The highest value of the ratio was reached at atheromatous samples, then calcified and normal ones R2 = 3.51 +/- 0.62, R3 = 1.63 +/- 0.31, R1 = 1.51 +/- 0.15 respectively. Statistically significant difference was noted between group two and one and between group two and three R2 = 3.51 +/- 0.62 vs R3 = 1.63 +/- 0.31 (p < 0,05); R2 = 3.51 +/- 0.62 vs. R1 = 1.51 +/- 0.15 (p<0.05) respectively. Conclusions: the following in vitro study confirms that photosensitizer chlorin e6 accumulates within atheromatous plaque. It may be a specific tool for atheromatous and normal or calcified segments discrimination. The advantage of the above method is a possibility of a real time imaging followed by targeted therapy of various forms and stages of atherosclerosis.

Bialy, Dariusz; Derkacz, Arkadiusz; Wawrzynska, M.; Kwasny, Miroslaw; Strek, Wieslaw; Protasiewicz, Marcin

2004-07-01

339

COLLATERALS DRAMATICALLY ALTER STROKE RISK IN INTRACRANIAL ATHEROSCLEROSIS  

PubMed Central

Objective Stroke risk due to intracranial atherosclerosis increases with degree of arterial stenosis. We evaluated the previously unexplored role of collaterals in modifying stroke risk in intracranial atherosclerosis and impact on subsequent stroke characteristics. Methods Collateral flow was graded in blind fashion on 287/569 baseline angiograms (stenoses of 50–99% and adequate collateral views) in the WASID trial. Statistical models predicted stroke in the symptomatic arterial territory based on collateral flow grade, percentage of stenosis, and previously demonstrated independent covariates. Results Across all stenoses, extent of collaterals was a predictor for subsequent stroke in the symptomatic arterial territory (HR none vs. good: 1.14, 95% CI 0.39 to 3.30, poor vs good: 4.36, 95% CI 1.46 to 13.07, p<0.0001). For 70–99% stenoses, more extensive collaterals diminished risk of subsequent territorial stroke (HR none vs. good: 4.60, 95% CI 1.03 to 20.56, poor vs good: 5.90, 95% CI 1.25 to 27.81, p=0.0427). At milder degrees of stenoses (50–69%), presence of collaterals was associated with greater likelihood of subsequent stroke (HR none vs. good: 0.18, 95% CI 0.04 to 0.82, poor vs good: 1.78, 95% CI 0.37 to 8.57, p<0.0001). In multivariate analyses, extent of collaterals was an independent predictor for subsequent stroke in the symptomatic arterial territory (HR none vs. good: 1.62, 95% CI 0.52 to 5.11, poor vs good: 4.78, 95% CI 1.55 to 14.7, p=0.0019). Interpretation Collateral circulation is a potent determinant of stroke risk in intracranial atherosclerosis, demonstrating a protective role with severe stenoses and identifying more unstable milder stenoses.

Liebeskind, David S.; Cotsonis, George A.; Saver, Jeffrey L.; Lynn, Michael J.; Turan, Tanya N.; Cloft, Harry J.; Chimowitz, Marc I.

2010-01-01

340

Increased atherosclerosis in streptozotocin-induced diabetic mice.  

PubMed Central

Premature and extensive atheroscleroses involving renal, peripheral, and cardiovascular sites remain major complications of diabetes mellitus. Controversy exists as to the contribution of hyperglycemia versus elevated local or systemic concentrations of insulin to atherosclerosis risk. In this report, we developed the first murine model susceptible to both atherosclerosis and diabetes to determine which diabetogenic factors contribute to vascular disease. C57BL/6 and BALB/c mice were treated with multiple low-dose streptozotocin (STZ) or control citrate buffer and fed rodent chow or an atherogenic-promoting (Ath) diet for 12-20 wk. STZ treatment resulted in sustained hyperglycemia (250-420 mg/dl) and a modest reduction in plasma insulin levels for both strains regardless of diet. Citrate-treated C57BL/6 mice fed the Ath diet showed extensive oil red O-staining fatty streak aortic sinus lesions (20,537+/-2,957 micron2), the size of which did not differ for Ath-fed mice treated with STZ (16,836+/-2,136 micron2). In contrast, hyperglycemic BALB/c mice fed the Ath diet showed a 17-fold increase in atherosclerotic lesion area (7,922+/-2,096 micron2) as compared with citrate-treated mice fed the Ath diet (467+/-318 micron2). Correlations between lesion size and plasma glucose levels were significant for BALB/c (r = 0.741, P < 0.009), but not C57BL/6 (r = 0.314, P<0.3) mice. Lesion size correlated significantly with plasma cholesterol for C57BL/6 (r = 0.612, P<0.03) but not BALB/c (r = 0.630, P<0.1) mice. Immunohistochemistry showed that aortic sinus lesions from both strains contained macrophages, but smooth muscle cells were clearly present in lesions of BALB/c mice. In summary, we present the first small animal model showing accelerated atherosclerosis in response to hyperglycemia. Fatty streaks resembled those of human type II lesions in that both macrophages and smooth muscle cells were evident. In addition, our results support the concept that hyperglycemia as opposed to hyperinsulinemia contributes heavily to risk of atherosclerosis.

Kunjathoor, V V; Wilson, D L; LeBoeuf, R C

1996-01-01

341

[Novel therapy for atherosclerosis and inflammatory vascular disease].  

PubMed

How to manage residual atherosclerosis risk after the statin therapy is a major concern in cardiovascular medicine. In addition to life-style modifications, new drugs against atherosclerotic and inflammatory vascular diseases are expected. In current clinical trials, phospholipase A2 inhibitors(darapladib, varespladib), RVX-208, D-4F, CETP inhibitors (anacetrapib, dalcetrapib), succinobucol are investigated. Some has been failed, but others are still promising. On molecular target basis of PAF-AH, CETP, PON, ABC transporters of A1 and G1, SR-BI, HO-1, potential benefits and side effects are discussed. PMID:21226269

Inazu, Akihiro

2011-01-01

342

[Determination of the intelligence quotient of pilots with incipient atherosclerosis].  

PubMed

Comprehensive examination, including clinical-functional and psychological testing, was given to 189 essentially healthy civil pilots and 235 pilots with atherosclerosis of aorta and trunks without considerable blood flow disturbance. The total of 835 investigations was performed. Distribution into health groups was conducted on clinical diagnosis. Pilots with cardiovascular pathologies were found to have the intelligence quotient significantly lowered. Associated clinical and psychological tests were effective in revealing and dynamic monitoring of incipient diseases, and taking reasoned disposition regarding pilot's fitness for flight duties. PMID:17405281

Krapivnitskaia, T A

343

Adipose triglyceride lipase in immune response, inflammation, and atherosclerosis  

PubMed Central

Consistent with its central importance in lipid and energy homeostasis, lipolysis occurs in essentially all tissues and cell types, including macrophages. The hydrolytic cleavage of triacylglycerol by adipose triglyceride lipase (ATGL) generates non-esterified fatty acids, which are subsequently used as essential precursors for lipid and membrane synthesis, mediators in cell signaling processes or as energy substrate in mitochondria. This review summarizes the current knowledge concerning the consequences of ATGL deficiency in macrophages with particular emphasis on macrophage (dys)-function, apoptosis, and atherosclerosis.

Radovic, Branislav; Aflaki, Elma; Kratky, Dagmar

2012-01-01

344

Sexual dimorphism in rodent models of hypertension and atherosclerosis  

PubMed Central

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

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

2012-01-01

345

Atherosclerosis starts in childhood--fact, myth or insinuation?  

PubMed

There is evidence that atherosclerotic vascular disease is observed already in childhood. The data on epidemiology, geographical variation and incidence is incomplete, and several risk factors have been identified and described. It is hoped that international collaborative research studies such as that on the effect of differences in nutrition or diabetes control in children, between our clinic and the Valle Hebron Children Hospital in Barcelona (sponsored by the Child Health Foundation) will generate knowledge on how to prevent premature atherosclerosis in childhood diabetes. PMID:1877290

Laron, Z

346

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

347

Serum semicarbazide-sensitive amine oxidase (SSAO) activity is an independent marker of carotid atherosclerosis  

Microsoft Academic Search

Background: Clinical and experimental studies suggest that increased activity of semicarbazide-sensitive amine oxidase (SSAO) and the production of cytotoxic metabolites (e.g., formaldehyde and hydrogen peroxide) may play an important role in the pathogenesis of atherosclerosis. The present study was designed to assess the relationship between the increased activity of the enzyme and the severity of atherosclerosis in diabetic and control

István Karádi; Zsuzsa Mészáros; Attila Csányi; Tamás Szombathy; Nóra Hosszúfalusi; László Romics; Kálmán Magyar

2002-01-01

348

Vitamin E supplementation and atherosclerosis : Epidemiological studies in smokers and elderly  

Microsoft Academic Search

The antioxidant vitamin E may have beneficial effects on several indicators of human health. We studied the impact on atherosclerosis, immune response and total mortality in smokers and elderly people, who are at risk for increased oxidative stress. Vitamin E may exert its effect on atherosclerosis by protecting low density lipoprotein (LDL) against lipid peroxidation. Moreover, lipid peroxidation may also

Waart de F. G

2000-01-01

349

Clinical trials of antioxidants in atherosclerosis: are we doing the right thing?  

Microsoft Academic Search

The hypothesis that oxidative modification of low density lipoprotein contributes to the progression of atherosclerosis is supported by an impressive body of in-vitro findings and by persuasive results in animal models of atherosclerosis. The hypothesis was originally proposed specifically to account for foam cell formation but oxidation of LDL has now been shown to confer on it a long list

D. Steinberg

1995-01-01

350

Alcohol consumption and coronary atherosclerosis progression—the Stockholm Female Coronary Risk Angiographic Study  

Microsoft Academic Search

Objective: To assess the association of alcohol intake with progression of coronary atherosclerosis. Although moderate drinkers have a lower risk of coronary heart disease than abstainers, the relation of alcohol use and coronary atherosclerosis has not been well studied. Methods and results: In the Stockholm Female Coronary Risk Angiographic Study, we evaluated 103 women, aged 65 years or younger, hospitalized

Imre Janszky; Kenneth J. Mukamal; Kristina Orth-Gomér; Anders Romelsjö; Karin Schenck-Gustafsson; Bertil Svane; Richard L. Kirkeeide; Murray A. Mittleman

2004-01-01

351

Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans  

Microsoft Academic Search

Little is known regarding the long-term effects of caloric restriction (CR) on the risk for atherosclerosis. We evaluated the effect of CR on risk factors for atherosclerosis in individuals who are restricting food intake to slow aging. We studied 18 individuals who had been on CR for an average of 6 years and 18 age-matched healthy individuals on typical American

Luigi Fontana; Timothy E. Meyer; Samuel Klein; John O. Holloszy

2004-01-01

352

Detection of radiation-induced, accelerated atherosclerosis in patients with osteoradionecrosis by panoramic radiography  

Microsoft Academic Search

Purpose: Osteoradionecrosis (ORN) of the mandible has long been considered the most destructive complication of head and neck irradiation. Recently, therapeutic irradiation has been implicated as the cause of induced\\/accelerated atherosclerosis of the cervical carotid artery and subsequent stroke. Panoramic radiography, previously shown to be capable of identifying carotid artery atherosclerosis in nonirradiated individuals, was used to assess the carotid

Arthur H Friedlander; Ralph M Eichstaedt; Ida K Friedlander; Paul M Lambert

1998-01-01

353

Effects of Stress Reduction on Carotid Atherosclerosis in Hypertensive African Americans  

Microsoft Academic Search

Background and Purpose—African Americans suffer disproportionately higher cardiovascular disease mortality rates than do whites. Psychosocial stress influences the development and progression of atherosclerosis. Carotid intima-media thickness (IMT) is a valid surrogate measure for coronary atherosclerosis, is a predictor of coronary outcomes and stroke, and is associated with psychosocial stress factors. Stress reduction with the Transcendental Meditation (TM) program decreases coronary

Amparo Castillo-Richmond; Robert H. Schneider; Charles N. Alexander; Robert Cook; Hector Myers; Sanford Nidich; Chinelo Haney; Maxwell Rainforth; John Salerno

2000-01-01

354

Modification of Biochemical and Cellular Processes in the Development of Atherosclerosis by Red Wine  

Microsoft Academic Search

Atherosclerosis is commonly associated with unstable angina and acute myocardial infarction. It occurs as a result of a cascade of events caused by various environmental, dietary, genetic, and inflammatory factors. Different epidemiological studies have suggested that moderate amounts of red wine consumption reduce the risk of complications associated with atherosclerosis. This contention is further supported by a variety of experimental

HARJOT K. SAINI; Parambir Dhami; Yan-Jun Xu; Sukhinder Cheema; Amarjit Arneja; Naranjan Dhalla

355

Serum magnesium concentrations in type 1 diabetic patients: Relation to early atherosclerosis  

Microsoft Academic Search

Hypomagnesemia and sub-clinical atherosclerosis are common in type 1 diabetic patients, and are especially common in poorly controlled and chronically treated diabetics. The aim of this study was to evaluate the relationships between serum magnesium (Mg) and intima-media thickness (IMT), and functions of common carotid artery (CCA), accepted as markers of early carotid atherosclerosis in type 1 diabetic patients. Serum

Mehmet Emre Atabek; Selim Kurtoglu; Ozgur Pirgon; Murat Baykara

2006-01-01

356

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

357

Association of circulating leukocyte count with coronary atherosclerosis regression after pravastatin treatment  

Microsoft Academic Search

Epidemiological studies have demonstrated that the peripheral blood leukocyte count could be used as a marker of the progression of atherosclerosis. Few data exist regarding the relationship between inhibition of the progression of coronary atherosclerosis and the anti-inflammatory effects of statins, especially the drugs’ effects on the leukocyte count in patients with coronary artery disease. A 6-month prospective study was,

Shigemasa Tani; Ken Nagao; Takeo Anazawa; Hirofumi Kawamata; Kiyoshi Iida; Michiaki Matsumoto; Yuichi Sato; Atsushi Hirayama

2008-01-01

358

Obesity, atherosclerosis and the vascular endothelium: mechanisms of reduced nitric oxide bioavailability in obese humans  

Microsoft Academic Search

It is now well established that obesity is an independent risk factor for the development of coronary artery atherosclerosis. The maintenance of vascular homeostasis is critically dependent on the continued integrity of vascular endothelial cell function. A key early event in the development of atherosclerosis is thought to be endothelial cell dysfunction. A primary feature of endothelial cell dysfunction is

IL Williams; SB Wheatcroft; AM Shah; MT Kearney

2002-01-01

359

Carotid Wall Thickness is Predictive of Incident Clinical Stroke The Atherosclerosis Risk in Communities (ARIC) Study  

Microsoft Academic Search

Few studies have determined whether carotid artery intima-media thickness (IMT) is associated prospectively with risk of first ischemic stroke. In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measured by B-mode ultrasonography at six sites of the carotid arteries. The authors assessed the relation of mean IMT to

Lloyd E. Chambless; Aaron R. Folsom; Limin X. Clegg; A. Richey Sharrett; Eyal Shahar; F. Javier Nieto; Wayne D. Rosamond; Greg Evans

360

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

Microsoft Academic Search

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

Justin M Lee; David R Greaves; Robin P Choudhury

2005-01-01

361

Natural Killer T Cells and Atherosclerosis: Form and Function Meet Pathogenesis  

Microsoft Academic Search

Atherosclerosis is a chronic inflammatory disease characterized by dyslipidemia and accumulation of lipids in the arterial intima, with activation of both innate and adaptive immunity. Reciprocally, dyslipidemia associated with atherosclerosis can perturb normal immune function. Natural killer T (NKT) cells are a specialized group of immune cells that share characteristics with both conventional T cells and natural killer cells. However,

Nicole A. Braun; Roman Covarrubias; Amy S. Major

2010-01-01

362

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

ERIC Educational Resources Information Center

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

Manchester, Ralph A.; Greenland, Philip

1987-01-01

363

Defibrotide Normalizes Cardiovascular Function Hampered by Established Atherosclerosis in the Rabbit  

Microsoft Academic Search

In a previous paper we gave evidence that chronic oral defibrotide antagonizes the noxious effect of developing atherosclerosis in the cardiovascular system. In the present paper we give evidence that defibrotide is still capable of exerting beneficial effects on cardiovascular function once atherosclerosis is established. In fact, there was statistically significant amelioration by defibrotide infusion in the following, all of

Giuseppe Rossoni; Ferruccio Berti; Fabio Trento; Franco Cattaneo; Roberto Porta; Rodolfo Pescador; Laura Ferro

2000-01-01

364

Quantum entanglement suppression  

NASA Astrophysics Data System (ADS)

Individuality of microparticles (e.g., of ions or atoms) interacting with their environments (e.g., with the solvent molecules) is an open question of both physical and chemical kinetic theories. A qualitative proposal of Primas, and its later elaboration due to Amann, offers a background in this regard. Actually, they suggest that suppression of quantum entanglement provides a basis for the solution of the problem. Here, we show that the model of the so-called DISD ("decoherence-induced suppression of decoherence") method naturally and straightforwardly fits the basic assumptions of Amann's proposal and, therefore, might represent the missing link to the complete solution of the problem at hand.

Dugic, M.

2002-10-01

365

P2 receptors: new potential players in atherosclerosis  

PubMed Central

Atherosclerosis is a focal inflammatory disease of the arterial wall. It starts with the formation of fatty streaks on the arterial wall that evolve to form a raised plaque made of smooth muscle cells (SMCs), and infiltrating leukocytes surrounding a necrotic core. The pathogenesis of the atherosclerotic lesion is incompletely understood, but it is clear that a dysfunction of the endothelium, recruitment and activation of inflammatory cells and SMC proliferation have a pivotal role. Over recent years receptors for extracellular nucleotides, the P2 receptors, have been recognized as fundamental modulators of leukocytes, platelets, SMCs and endothelial cells. P2 receptors mediate chemotaxis, cytokine secretion, NO generation, platelet aggregation and cell proliferation in response to accumulation of nucleotides into the extracellular milieu. Clinical trials have shown the benefit of antagonists of the ADP platelet receptor(s) in the prevention of vascular accidents in patients with atherosclerosis. Therefore, we anticipate that a deeper understanding of the involvement of P2 receptors in atheroma formation will open new avenues for drug design and therapeutic intervention.

Virgilio, Francesco Di; Solini, Anna

2002-01-01

366

Role of Suppressor of Cytokine Signaling-1 In Murine Atherosclerosis  

PubMed Central

Background While the impact of inflammation as the substantial driving force of atherosclerosis has been investigated in detail throughout the years, the influence of negative regulators of pro-atherogenic pathways on plaque development has remained largely unknown. Suppressor of cytokine signaling (SOCS)-1 potently restricts transduction of various inflammatory signals and, thereby modulates T-cell development, macrophage activation and dendritic cell maturation. Its role in atherogenesis, however has not been elucidated so far. Methods and Results Loss of SOCS-1 in the low-density lipoprotein receptor deficient murine model of atherosclerosis resulted in a complex, systemic and ultimately lethal inflammation with increased generation of Ly-6Chi monocytes and activated macrophages. Even short-term exposure of these mice to high-cholesterol dieting caused enhanced atherosclerotic plaque development with accumulation of M1 macrophages, Ly-6C positive cells and neutrophils. Conclusion Our data not only imply that SOCS-1 is athero-protective but also emphasize the fundamental, regulatory importance of SOCS-1 in inflammation-prone organisms.

Hillmer, Anja; Lumpe, Stefan; Grote, Karsten; Ballmaier, Matthias; Bleich, Andre; Glage, Silke; Tietge, Uwe J. F.; Luchtefeld, Maren; Schieffer, Bernhard

2012-01-01

367

Particulate air pollution, systemic oxidative stress, inflammation, and atherosclerosis.  

PubMed

Air pollution has been associated with significant adverse health effects leading to increased overall morbidity and mortality of worldwide significance. Epidemiological studies have shown that the largest portion of air pollution-related mortality is due to cardiovascular diseases, predominantly those of ischemic nature. Human studies suggest an association with atherosclerosis and increasing experimental animal data support that this association is likely to be causal. While both gasses and particles have been linked to detrimental health effects, more evidence implicates the particulate matter (PM) components as major responsible for a large portion of the proatherogenic effects. Multiple experimental approaches have revealed the ability of PM components to trigger and/or enhance free radical reactions in cells and tissues, both ex vivo as well as in vivo. It appears that exposure to PM leads to the development of systemic prooxidant and proinflammatory effects that may be of great importance in the development of atherosclerotic lesions. This article reviews the epidemiological studies, experimental animal, and cellular data that support the association of air pollutants, especially the particulate components, with systemic oxidative stress, inflammation, and atherosclerosis. It also reviews the use of transcriptomic studies to elucidate molecular pathways of importance in those systemic effects. PMID:21461032

Araujo, Jesus A

2010-11-10

368

Antioxidant vitamins in atherosclerosis--animal experiments and clinical studies.  

PubMed

Atherosclerotic heart diseases are universal problems in modern society. Oxidative damage to lipids is a primary cause of atherosclerosis. There are many choices for treatment, but no definite recommendations to prevent the occurrence of the disease. There is a relationship between atherosclerotic risk factors and increased vascular production of reactive oxygen species (ROS). Oxidized low-density lipoproteins (LDL) and ROS may directly cause endothelial dysfunction by reducing endothelial nitric oxide (NO) bioavailability. Vitamin E can to some degree prevent the consequences of oxidized LDL, and vitamin C provides NO synthase activity. Although prolonged use of vitamin A, C, and E supplementation in pharmaceutical forms has been proven to be effective in preventing atherosclerosis in animal experiments, this has not yet been demonstrated in clinical trials with human beings. It should be taken into account that the evidence has been gathered from young/adult experimental animals with early stages of arthrosclerosis and from in-vitro studies, while most of the clinical trials have involved older patients with late stages of the disease. Prolonged use of vitamins in the diet has not yet been recommended in human beings. There is some indication that a diet rich in antioxidant fruit and vegetables may be beneficial in the prevention of cardiovascular events. PMID:23214308

Ozkanlar, Seckin; Akcay, Fatih

369

BHUx: a patented polyherbal formulation to prevent hyperlipidemia and atherosclerosis.  

PubMed

Since hyperlipidemia, inflammation and obesity are closely related to atherosclerosis, therefore management of these factors together would be beneficial for overall treatment approach for atherosclerosis. Although, Indian system of medicine, especially Ayurveda has several medicinal plants with proven beneficial claims towards these pathological conditions, but most of them lack enough experimental data. BHUx is a novel polyherbal formulation, consisting of 5 medicinal plants namely Termenalia arjuna, Strychnox nux vomica, Boswellia serrata, Commiphora mukul, and Semecarpus anacardium, which have history of clinical use as single or in other combinations, but these plant fractions were never tried collectively in this ratio as in BHUx, which has been found to be effective on all the etiological factors, together. In this paper, antioxidant, anti-inflammatory, hypo-lipidemic, anti-proliferative properties of BHUx have been studied on several experimental models based on chemical tests, cell culture, in vitro models, and in vivo experiments with normal and transgenic animals. A separate pre-clinical toxicity study has also been carried out to prove its safety margin in therapeutic doses. Further, clinical trail of BHUx is under way, before it comes to market for public use as functional food to maintain healthy heart. This article also review some patent related to the field. PMID:19149746

Tripathi, Yamini B

2009-01-01

370

Molecular chaperones and heat shock proteins in atherosclerosis  

PubMed Central

In response to stress stimuli, mammalian cells activate an ancient signaling pathway leading to the transient expression of heat shock proteins (HSPs). HSPs are a family of proteins serving as molecular chaperones that prevent the formation of nonspecific protein aggregates and assist proteins in the acquisition of their native structures. Physiologically, HSPs play a protective role in the homeostasis of the vessel wall but have an impact on immunoinflammatory processes in pathological conditions involved in the development of atherosclerosis. For instance, some members of HSPs have been shown to have immunoregulatory properties and modification of innate and adaptive response to HSPs, and can protect the vessel wall from the disease. On the other hand, a high degree of sequence homology between microbial and mammalian HSPs, due to evolutionary conservation, carries a risk of misdirected autoimmunity against HSPs expressed on the stressed cells of vascular endothelium. Furthermore, HSPs and anti-HSP antibodies have been shown to elicit production of proinflammatory cytokines. Potential therapeutic use of HSP in prevention of atherosclerosis involves achieving optimal balance between protective and immunogenic effects of HSPs and in the progress of research on vaccination. In this review, we update the progress of studies on HSPs and the integrity of the vessel wall, discuss the mechanism by which HSPs exert their role in the disease development, and highlight the potential clinic translation in the research field.

Xu, Qingbo; Metzler, Bernhard; Jahangiri, Marjan

2012-01-01

371

Aortic smooth muscle cell proteoglycan synthesis in relation to atherosclerosis  

SciTech Connect

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

Edwards, I.J.

1989-01-01

372

Radionuclide imaging of experimental atherosclerosis with nonspecific polyclonal immunoglobulin G  

SciTech Connect

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

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

1989-06-01

373

Photodynamic diagnosis and treatment for atherosclerosis by an endoscopic approach.  

PubMed

The photosensitizer, mono-L-aspartyl chlorin e6 (NPe6), specifically accumulates in the atheromatous plaque. We detected the fluorescence spectra of NPe6 emitted from atheromatous plaques on the descending thoracic aorta by an angioscopic approach using the animal model of atherosclerosis. We also showed that a fluorescence spectrum peak at 675 nm was obtained laparoscopically only in parts of the abdominal aorta with an atheromatous plaque. By a fluorescence endoscope, atheromatous plaques on the carotid artery were recognized as reddish spots from outside the artery. In addition, we visualized specifically at the beating heart surface small coronary atherosclerosis using an epifluorescence stereoscope system.We examined the effects of photodynamic treatment with NPe6 on the atheromatous plaque. The change in the elastic framework in the atheromatous plaque after photodynamic treatment was evaluated using scanning electron microscopy. The destruction of the architecture of the elastic fiber network in the atheromatous plaque was revealed. We also studied the change in the lipid components of the atheromatous plaque using Fourier transform infrared (FTIR) microspectroscopy. FTIR microspectroscopic analysis showed a dissociation of ester bonds of cholesterol esters in the atheromatous plaque after photodynamic treatment. The framework of the atheromatous plaque and the lipids accumulated in the plaque could be destroyed following such treatment. PMID:18493502

Hayashi, J; Saito, T; Aizawa, K

1999-01-01

374

Association between MIF gene polymorphisms and carotid artery atherosclerosis.  

PubMed

Atherosclerosis is a chronic inflammatory disorder. Macrophage migration inhibitory factor (MIF) is a potent cytokine that plays an important role in the regulation of immune responses. Polymorphisms including five- to eight-repeat CATT variants ((CATT)(5-8)) and G-173C in the promoter region of the MIF gene are associated with altered levels of MIF gene transcription. The purpose of the study is to investigate the relationship between promoter polymorphisms of the MIF gene and the severity of carotid artery atherosclerosis (CAA). The severity of CAA was assessed in 593 individuals with a history of ischemic stroke by using sonographic examination, and the MIF promoter polymorphisms of these individuals were genotyped. The carriage of (CATT)7 (compared to genotypes composed of (CATT)5, (CATT)6, or both), carriage of C allele (compared to GG), and carriage of the haplotype (CATT)7-C (compared to genotypes composed of (CATT)5-G, (CATT)6-G, or both) were significantly associated with an increase in the severity of CAA. We conclude that polymorphisms in the MIF gene promoter are associated with CAA severity in ischemic stroke patients. These genetic variants may serve as markers for individual susceptibility to CAA. PMID:23537651

Lan, Min-Yu; Chang, Yung-Yee; Chen, Wei-Hsi; Tseng, Yu-Lung; Lin, Hung-Sheng; Lai, Shung-Lon; Liu, Jia-Shou

2013-03-26

375

Monitoring SERS-based contrast agents in atherosclerosis experimental models  

NASA Astrophysics Data System (ADS)

There have been enormous progresses in developing a class of multimodal contrast agents, which combine MRI with optical imaging. Contrast agent targeting can provide enhanced diagnostic information, allowing differentiation between variable and stable atherosclerotic plaques. Recently an intensive efforts have been working on the development of contrast agents that can improve the ability to detect and characterize atherosclerosis in clinical and preclinical applications. Earlier studies on hyperlipidemic rabbits using in vivo MRI have shown accumulation of USPIOs in plaques with a high macrophage content that induces magnetic resonance (MR) signal changes correlated to the absolute iron content in the aortic arch. A potent new class of nanoparticles contrast agents have recently drawn much attention for its wide diverse diagnostic and potential therapeutic applications particularly in monitoring the inflammatory responses. In our previous studies we have investigated SPIO contrast agents uptakes in hepatic and spleen tissues taken from NZW rabbits. The scope of this work encompasses application of an emerging hybrid imaging modality, SERSbased nonlinear optical microscopy, in investigating atherosclerosis experimental models. In this work experiments are performed on contrast treated tissue sections taken from aortic arch of atherosclerotic animal model. Marked contrast enhancement has been observed in the treated aortic sections compared with the untreated control. The obtained images are compared with immunohistochemistry .The work presented can be promising for future studies on in vivo detection of macrophages in human plaques and early detection of atherosclerotic diseases.

Machtoub, Lina H.

2011-02-01

376

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

377

Possible involvement of sulfane sulfur in homocysteine-induced atherosclerosis.  

PubMed

Homocysteinemia, first identified as a genetic disease in children in the 1960s, is associated with severe widespread atherosclerosis which causes death (in untreated cases) before the age of 10 years. Elevated blood homocysteine is now recognized as a risk factor for heart disease in the general population. The mechanism by which homocysteine induces atherosclerosis is still unknown despite intensive investigation. It is proposed here that the mechanism involves sulfane sulfur formed in the catabolism of homocysteine. This unstable and reactive form of sulfur is formed through the action of several enzymes which are known to use homocysteine, its disulfide (homocystine), or its mixed disulfide with cysteine as substrates. Sulfane sulfur has physiological effects which are consistent with a role in atherogenesis. At very low concentrations, it induces proliferation of many cell types, an effect which is consistent with the fibrosis and hyperplasia, which are prominent features of atherosclerotic lesions. At higher concentrations, it is toxic. Also, it modulates the activity of many enzymes and, through this effect on enzymes of lipid metabolism, it could be responsible for the lipid accumulation seen in atherosclerotic lesions. PMID:11425300

Toohey, J I

2001-02-01

378

An update on advanced glycation endproducts and atherosclerosis.  

PubMed

Advanced glycation endproducts (AGEs) are a group of modified molecular species formed by nonenzymatic reactions between the aldehydic group of reducing sugars with proteins, lipids, or nucleic acids. Formation and accumulation of AGEs are related to the aging process and are accelerated in diabetes. AGEs are generated in hyperglycemia, but their production also occurs in settings characterized by oxidative stress and inflammation. These species promote vascular damage and acceleration of atherosclerotic plaque progression mainly through two mechanisms: directly, altering the functional properties of vessel wall extracellular matrix molecules, or indirectly, through activation of cell receptor-dependent signaling. Interaction between AGEs and the key receptor for AGEs (RAGE), a transmembrane signaling receptor which is present in all cells relevant to atherosclerosis, alters cellular function, promotes gene expression, and enhances the release of proinflammatory molecules. The importance of the AGE-RAGE interaction and downstream pathways, leading to vessel wall injury and plaque development, has been amply established in animal studies. Moreover, the deleterious link of AGEs with diabetic vascular complications has been suggested in many human studies. Blocking the vicious cycle of AGE-RAGE axis signaling may be essential in controlling and preventing cardiovascular complications. In this article, we review the pathogenetic role of AGEs in the development, progression and instability of atherosclerosis, and the potential targets of this biological system for the prevention and treatment of cardiovascular disease. PMID:22488968

Del Turco, Serena; Basta, Giuseppina

2012-04-10

379

Lipid glycation and protein glycation in diabetes and atherosclerosis.  

PubMed

Recent instrumental analyses using a hybrid quadrupole/linear ion trap spectrometer in LC-MS/MS have demonstrated that the Maillard reaction progresses not only on proteins but also on amino residues of membrane lipids such as phosphatidylethanolamine (PE), thus forming Amadori-PE (deoxy-D: -fructosyl PE) as the principal products. The plasma Amadori-PE level is 0.08 mol% of the total PE in healthy subjects and 0.15-0.29 mol% in diabetic patients. Pyridoxal 5'-phosphate and pyridoxal are the most effective lipid glycation inhibitors, and the PE-pyridoxal 5'-phosphate adduct is detectable in human red blood cells. These findings are beneficial for developing a potential clinical marker for glycemic control as well as potential compounds to prevent the pathogenesis of diabetic complications and atherosclerosis. Glucose and other aldehydes, such as glyoxal, methylglyoxal, and glycolaldehyde, react with the amino residues of proteins to form Amadori products and Heynes rearrangement products. Because several advanced glycation end-product (AGE) inhibitors such as pyridoxamine and benfotiamine inhibit the development of retinopathy and neuropathy in streptozotocin (STZ)-induced diabetic rats, AGEs may play a role in the development of diabetic complications. In the present review, we describe the recent progress and future applications of the Maillard reaction research regarding lipid and protein modifications in diabetes and atherosclerosis. PMID:20957396

Miyazawa, Teruo; Nakagawa, Kiyotaka; Shimasaki, Satoko; Nagai, Ryoji

2010-10-19

380

Mammographically Detectable Breast Arterial Calcification And Atherosclerosis: A Review.  

PubMed

Breast artery calcification (BAC), observed as an incidental finding on screening mammograms, represents degenerative calcific changes occurring in the mammary arteries, increasing with age. The aim of this review is to discuss relevant literature examining relationship 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 was 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 (CAD), cardiovascular disease (CVD), stroke, cerebral artery disease, carotid and peripheral artery diseases and coronary artery calcification. A majority of the studies showed a statistically significant relationship between BAC and the presence of CAD and CVD, as well as associated mortality. Sensitivity of BAC in predicting CV events was low, specificity was high. BAC was predictive of incident and prevalent stroke but not stroke mortality. Similarly, BAC was predictive of cerebral, carotid and peripheral artery disease. Thus, 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

2013-04-11

381

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.

Weber, Christian; Meiler, Svenja; Doring, 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.; Forster, Irmgard; Zenke, Martin; Hieronymus, Thomas; Junt, Tobias; Zernecke, Alma

2011-01-01

382

Anti-inflammatory and anti-atherogenic role of BMP receptor II in atherosclerosis.  

PubMed

Evaluation of: Kim CW, Song H, Kumar S et al. Anti-inflammatory and anti-atherogenic role of BMP receptor II in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 33, 1350-1359 (2013). Increased expression of BMPs in atherosclerosis suggested that the knockdown of the receptor mediating BMP action would prevent endothelial inflammation and atherosclerosis. Based on this hypothesis, Kim et al. performed a series of experiments in which the effect of BMP receptor type II (BMPRII) knockout was tested in in vitro and in vivo models of atherogenesis. Unexpectedly, they found that the loss of BMPRII induces endothelial inflammation and atherosclerosis. Knockdown of BMPRII in endothelial cells induced monocyte adhesion through the expression of ICAM-1 and VCAM-1. The loss of BMPRII induced endothelial inflammation and atherosclerosis in apoE-deficient mice. Besides, BMPRII expression was gradually lost over the course of atherosclerosis progression in human coronary arteries. PMID:24020661

Simic, Tatjana

2013-09-01

383

Suppressing the Zs.  

ERIC Educational Resources Information Center

|In the frameword of generalized phrase-structure grammar, possessive clitics (POSS), bound words (BWs), and phrasal affixes (PAs) are analyzed. It is argued that English POSS should be treated as an edge-located inflectional affix, since POSS is suppressed in the presence of other Z affixes (plural, other possessives). (Author/LMO)|

Zwicky, A. M.

1987-01-01

384

Sensory suppression during feeding  

PubMed Central

Feeding is essential for survival, whereas withdrawal and escape reactions are fundamentally protective. These critical behaviors can compete for an animal's resources when an acutely painful stimulus affects the animal during feeding. One solution to the feeding-withdrawal conflict is to optimize feeding by suppressing pain. We examined whether rats continue to feed when challenged with a painful stimulus. During feeding, motor withdrawal responses to noxious paw heat either did not occur or were greatly delayed. To investigate the neural basis of sensory suppression accompanying feeding, we recorded from brainstem pain-modulatory neurons involved in the descending control of pain transmission. During feeding, pain-facilitatory ON cells were inhibited and pain-inhibitory OFF cells were excited. When a nonpainful somatosensory stimulus preactivated ON cells and preinhibited OFF cells, rats interrupted eating to react to painful stimuli. Inactivation of the brainstem region containing ON and OFF cells also blocked pain suppression during eating, demonstrating that brainstem pain-modulatory neurons suppress motor reactions to external stimulation during homeostatic behaviors.

Foo, H.; Mason, Peggy

2005-01-01

385

Drug Insight: appetite suppressants  

Microsoft Academic Search

The term 'appetite suppressant' is used to denote drugs that act primarily on the neurochemical transmitters of the central nervous system to reduce food intake. In addition to drugs that release or mimic the effect of norepinephrine (noradrenaline), this could include drugs that inhibit: reuptake of norepinephrine or 5-hydroxytryptamine (also known as serotonin); bind to the ?-aminobutyric acid receptors or

George A Bray

2005-01-01

386

Ambient Air Pollution and the Progression of Atherosclerosis in Adults  

PubMed Central

Background Cross-sectional studies suggest an association between exposure to ambient air pollution and atherosclerosis. We investigated the association between outdoor air quality and progression of subclinical atherosclerosis (common carotid artery intima-media thickness, CIMT). Methodology/Principal Findings We examined data from five double-blind randomized trials that assessed effects of various treatments on the change in CIMT. The trials were conducted in the Los Angeles area. Spatial models and land-use data were used to estimate the home outdoor mean concentration of particulate matter up to 2.5 micrometer in diameter (PM2.5), and to classify residence by proximity to traffic-related pollution (within 100 m of highways). PM2.5 and traffic proximity were positively associated with CIMT progression. Adjusted coefficients were larger than crude associations, not sensitive to modelling specifications, and statistically significant for highway proximity while of borderline significance for PM2.5 (P?=?0.08). Annual CIMT progression among those living within 100 m of a highway was accelerated (5.5 micrometers/yr [95%CI: 0.13–10.79; p?=?0.04]) or more than twice the population mean progression. For PM2.5, coefficients were positive as well, reaching statistical significance in the socially disadvantaged; in subjects reporting lipid lowering treatment at baseline; among participants receiving on-trial treatments; and among the pool of four out of the five trials. Conclusion Consistent with cross-sectional findings and animal studies, this is the first study to report an association between exposure to air pollution and the progression of atherosclerosis – indicated with CIMT change – in humans. Ostensibly, our results suggest that air pollution may contribute to the acceleration of cardiovascular disease development – the main causes of morbidity and mortality in many countries. However, the heterogeneity of the volunteering populations across the five trials, the limited sample size within trials and other relevant subgroups, and the fact that some key findings reached statistical significance in subgroups rather than the sample precludes generalizations to the general population.

Kunzli, Nino; Jerrett, Michael; Garcia-Esteban, Raquel; Basagana, Xavier; Beckermann, Bernardo; Gilliland, Frank; Medina, Merce; Peters, John; Hodis, Howard N.; Mack, Wendy J.

2010-01-01

387

Prospects for prevention of atherosclerosis in the young.  

PubMed

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

Kannel, W B

1976-10-01

388

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.

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

389

Atherosclerosis in coronary artery and aorta in a semi-urban population by applying modified American Heart Association classification of atherosclerosis: An autopsy study  

PubMed Central

Background: Ischemic heart disease (IHD) following atherosclerosis is a giant killer and the incidence of atherosclerosis in coronary arteries is rapidly increasing among Indians. The study was formulated to assess the histomorphological atherosclerotic changes in aorta and coronary arteries at autopsy by applying the modified American Heart Association classification of atherosclerosis based on morphological descriptions to find out the age and sex related prevalence of atherosclerosis in the semi-urban population of Kolar, a district in Southern India. Materials and Methods: Autopsy was conducted on 113 cases whose age ranged from 8-85 years. Autopsy was conducted by the conventional technique; heart and the aorta were removed and fixed in 10% formalin. The heart was dissected along the direction of flow of blood and aorta along the posterior surface. Microscopic assessment of the three main coronary arteries and aorta was done using the modified American Heart Association classification of atherosclerosis. Proportions were analyzed using Chi-square test. Results: The number of males was 78 (69%) and number of females was 35 (31%). Mean age was 37.11 ± 15.69 years. Increased incidence of intermediate lesions was noted in young individuals (15-34 yrs). Atherosclerotic lesions were more in left anterior descending artery compared to other coronary arteries and in abdominal aorta compared to thoracic and ascending aorta. Vulnerable plaques were more in right coronary artery. Conclusion: With cardiovascular disease attaining pandemic proportions, the study of subclinical atherosclerosis is the need of the hour to estimate the disease burden in the asymptomatic population. The increased amount of atherosclerosis (advanced and intermediate lesions) found in the young population in this study gives an indication that anti-atherogenic preventive measures need to be implemented in young individuals, so as to prevent coronary artery disease from causing premature death.

Thej, Mothakapalli Jagadish; Kalyani, Raju; Kiran, Jayaramaiah

2012-01-01

390

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.

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

391

PET/MR imaging of atherosclerosis: initial experience and outlook  

PubMed Central

Hybrid scanners such as PET/CT have in the past emerged as a valuable modality in clinical routine as well as an important research tool. Recently, the newly developed fully integrated PET/MR scanners were introduced to the market, raising high expectations especially due to the excellent soft tissue contrast and functional imaging capabilities of MRI. In this issue of the American Journal of Nuclear Medicine and Molecular Imaging, initial experiences using a hybrid PET/MR scanner for carotid artery imaging in a group of patients with increased risk for atherosclerosis are described. This represents a proof-of-principle study, which could stimulate future applications of this powerful modality in atherosclerotic plaque imaging.

Rischpler, Christoph; Nekolla, Stephan G; Beer, Ambros J

2013-01-01

392

A study on tea-pigment in prevention of atherosclerosis.  

PubMed

Since Lou Fu-qing et al first reported that tea had effect on the prevention of atherosclerosis (AS) in the 1960s, we have conducted experimental and clinical studies, and found that tea-pigment (TP) could reduce blood coagulability, increase fibrinolysis, prevent platelet adhesion and aggregation, and decrease cholesterol content in aortic walls in vivo (P less than 0.01). In addition, TP was shown to inhibit the proliferation of cultured human aortic smooth muscle cells in normal and elevated LDL circumstance in vitro (P less than 0.01), and decreased the level of T x B2 in platelet-rich plasma and remote myocardial infarction patients (P less than 0.01). TP can be used in the prevention of AS. PMID:2517612

Lou, F Q; Zhang, M F; Zhang, X G; Liu, J M; Yuan, W L

1989-08-01

393

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.

Channon, Keith M.

2013-01-01

394

The occurrence of cerebrovascular atherosclerosis in Alzheimer's disease patients  

PubMed Central

Background: Both Alzheimer’s disease (AD) and cerebrovascular atherosclerosis (CA) contributed to dementia in an aged population. Whether they share the same mechanism is unknown. Aim: Our goal was to explore the occurrence rates of CA in AD patients. Method: Here we examined the degree of CA in different groups of AD patients with contrast angiography. Ninety-three AD patients were recruited to the present study. Contrast computed tomography scanning and contrast angiography were performed for CA analyses. Result: We found that the cerebrovascular plaques were common in AD patients, which was partly correlated with the severity of AD (as determined by cognitive decline). Conclusion: We concluded that vascular dementia may partly correlate with AD pathology.

Yuan, Jing; Wen, Ge; Li, Yingjia; Liu, Changxing

2013-01-01

395

Immunohistochemical study of intimal microvessels in coronary atherosclerosis.  

PubMed Central

Two hundred ninety-nine human coronary artery paraffin-embedded tissue blocks were examined for intimal microvessel invasion by probing for factor VIII-associated antigen with indirect immunofluorescence and high resolution confocal microscopy. The results obtained confirm that intimal microvessels originate in the adventitia and show that the richness of intimal microvessels is strongly positively correlated with intimal thickness and negatively correlated with relative lumen size. A number of plasma constituents were examined in serial sections. Comparison of immunofluorescence distribution patterns of these components with intimal microvessel distribution patterns reveals that intimal microvessels leak plasma albumin into artery walls, exude fibrinogen, and are associated with the build-up of plasma cells within atherosclerotic lesions. Therefore, intimal microvessels are demonstrated to play important roles in the development of atherosclerosis. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8

Zhang, Y.; Cliff, W. J.; Schoefl, G. I.; Higgins, G.

1993-01-01

396

Vibrotactile suppression of tinnitus  

NASA Astrophysics Data System (ADS)

At the Society's 142nd meeting, the efficacy of high frequency bone conducted stimulation in suppressing tinnitus was presented. The hypothesized mechanism was the reprogramming of frequency tuning of auditory neurons in the central nervous system, secondarily to peripheral hearing loss. This mechanism is unlikely in cases of tinnitus in the presence of normal audiometric sensitivity. There is the possibility that hearing loss above 10 kHz can play a role in tinnitus, an association not thoroughly explored. Somatomotor stimulation influencing the quality of tinnitus has been reported, as have interconnections of the auditory and somatosensory systems. There would appear to be an evolutionary advantage of linking the sensorimotor organization of the external ear and the auditory function of the brainstem in sound localization. Thus, stimulation of the pinna and post auricular area may be a means of suppressing tinnitus. To that end a thin aluminum ceramic bimorph was constructed to fit on the inner surface of the pinna. When driven by low (<100 Hz) and high (>10 kHz) frequencies multiplied by MHz carriers, demodulation in the skin resulted in vibrotactile stimulation. Tactile stimulation was an adjunct to the high frequencies resulting in a multimodal suppressive effect in a small pilot study.

Lenhardt, Martin L.

2002-05-01

397

Tactile suppression of displacement.  

PubMed

In vision, the discovery of the phenomenon of saccadic suppression of displacement has made important contributions to the understanding of the stable world problem. Here, we report a similar phenomenon in the tactile modality. When scanning a single Braille dot with two fingers of the same hand, participants were asked to decide whether the dot was stationary or whether it was displaced from one location to another. The stimulus was produced by refreshable Braille devices that have dots that can be swiftly raised and recessed. In some conditions, the dot was stationary. In others, a displacement was created by monitoring the participant's finger position and by switching the dot activation when it was not touched by either finger. The dot displacement was of either 2.5 mm or 5 mm. We found that in certain cases, displaced dots were felt to be stationary. If the displacement was orthogonal to the finger movements, tactile suppression occurred effectively when it was of 2.5 mm, but when the displacement was of 5 mm, the participants easily detected it. If the displacement was medial-lateral, the suppression effect occurred as well, but less often when the apparent movement of the dot opposed the movement of the finger. In such cases, the stimulus appeared sooner than when the brain could predict it from finger movement, supporting a predictive rather than a postdictive differential processing hypothesis. PMID:20842353

Ziat, Mounia; Hayward, Vincent; Chapman, C Elaine; Ernst, Marc O; Lenay, Charles

2010-09-15

398

Pattern recognition of magnetic resonance images with application to atherosclerosis  

SciTech Connect

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

Carman, C.S.

1989-01-01

399

Flow Shear Stress and Atherosclerosis: A Matter of Site Specificity  

PubMed Central

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

Nigro, Patrizia; Abe, Jun-ichi

2011-01-01

400

Vascular fluid mechanics, the arterial wall, and atherosclerosis.  

PubMed

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

Nerem, R M

1992-08-01

401

Exploring new indications for statins beyond atherosclerosis: Successes and setbacks.  

PubMed

Statins have been shown to reduce cardiovascular events across a broad spectrum of patients at risk, irrespective of baseline LDL-cholesterol levels. In a meta-analysis of 14 statin trials involving more than 90,000 participants, statin therapy reduced the 5-year incidence of cardiovascular events by about 20% for each mmol/L of LDL-cholesterol reduction. The results of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study suggest that the degree of reduction in Japanese subjects may be greater than this for the same degree of LDL-cholesterol reduction. Given the success of statins in preventing cardiovascular events, it is not surprising that they have been tested in a variety of related conditions, three of which are discussed in this article. Heart failure is characterized by inflammation, endothelial dysfunction and neurohumeral activation, conditions that are ameliorated by statin therapy. The Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) showed no significant benefit of rosuvastatin upon the primary endpoint, cardiovascular death, myocardial infarction and stroke. However, subgroups identified by the biomarkers plasma amino-terminal pro-brain natriuretic and C-reactive protein showed a reduction in events. Aortic stenosis and atherosclerosis share common risk factors, including hypertension and hypercholesterolemia. Although non-randomized cohort studies have suggested that statins slow the progression of aortic stenosis, this was not shown in either of the two randomized placebo-controlled trials testing this hypothesis. Similarly, Alzheimer's disease shares many risk factors with atherosclerosis, and several observational studies have reported a lower risk of developing this condition in patients taking statins. However, two recently completed clinical trials indicate that neither atorvastatin nor simvastatin slow the progression of early Alzheimer's disease. In conclusion, although statins are effective, established therapy for the prevention of vascular events in patients at risk, they have as yet not proven to be successful for these newer indications. PMID:20206067

Waters, David D

2010-01-07

402

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

403

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

404

Risk Factors for Atherosclerosis and the Development of Pre-Atherosclerotic Intimal Hyperplasia  

PubMed Central

Summary Intimal hyperplasia or thickening is considered to be the precursor lesion for atherosclerosis in humans; however the factors governing its formation are unclear. In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. Background Intimal hyperplasia, or thickening, is considered to be the precursor lesion for atherosclerosis in humans; however, the factors governing its formation are unclear. To gain insight into the etiology of pre-atherosclerotic intimal hyperplasia, traditional risk factors for atherosclerosis were correlated with the intimal hyperplasia in an atherosclerosis-resistant vessel, the internal thoracic artery. Methods Paired internal thoracic arteries were obtained from 89 autopsies. Multivariate logistic regression and multiple regression models were used to examine the association of pre-atherosclerotic intimal hyperplasia with traditional risk factors for atherosclerosis: age, gender, hypertension, smoking, body mass index, diabetes, and hypercholesterolemia. Results Atherosclerotic lesions consisting of fatty streaks and/or type III intermediate lesions were identified in 19 autopsies. Only age >75 years was found to be significantly correlated with atherosclerotic lesion development (P=0.01). Multiple regression model of the intima/media ratio in all 89 cases revealed age >75 years (P<0.0001), age 51–75years (P=0.0012), smoking (P=0.008) and hypertension (P=0.02) to be significantly correlated with intimal thickness. In the 70 cases without atherosclerosis, only age 51–75 years (P=0.006) and smoking (P=0.028) were found to be significantly associated with pre-atherosclerotic intimal thickening. Conclusions In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. These observations indicate that in some settings, intimal hyperplasia may be part of the disease process of atherosclerosis, and that its formation may be influenced by traditional risk factors for atherosclerosis.

Cizek, Stephanie M.; Bedri, Shahinaz; Talusan, Paul; Silva, Nilsa; Lee, Hang; Stone, James R.

2007-01-01

405

Relation of coronary artery disease and cerebrovascular disease with atherosclerosis of the thoracic aorta in the general population.  

PubMed

The association between clinical coronary artery disease, cerebrovascular disease, and aortic atherosclerosis has not been examined in the general population. Transesophageal echocardiography was performed in 581 subjects, a random sample of the Olmsted County (Minnesota) population aged >/=45 years, participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. The frequency and severity of atherosclerosis of the thoracic aorta were determined in the population and the association between clinical coronary artery disease, cerebrovascular disease, and aortic atherosclerosis was examined. Previous myocardial infarction, angina pectoris, and coronary artery bypass surgery were significantly associated with aortic atherosclerosis, adjusting for age and gender (p atherosclerosis, these manifestations were associated with complex atherosclerosis (plaques >4-mm thick, ulcerated plaques, or mobile debris), adjusting for age and gender (p <0.05). Age, smoking, pulse pressure, previous myocardial infarction (odds ratio [OR] 4.67; 95% confidence interval [CI] 1.42 to 15.40), and coronary artery bypass surgery (OR 5.12; 95% CI 1.01 to 26.01) were independently associated with aortic atherosclerosis. Among subjects with atherosclerosis, age, smoking, pulse pressure, hypertension treatment, and coronary artery disease (OR 2.50; 95% CI 1.18 to 5.30) were independently associated with complex atherosclerosis. Weak associations were observed between previous ischemic stroke, transient ischemic attack, and aortic atherosclerosis, associations that were not significant after age- and gender-adjustment (p >0.2). Thus, coronary artery disease is strongly associated with aortic atherosclerosis and complex atherosclerosis in the general population. Cerebrovascular disease is weakly associated with aortic atherosclerosis, thereby questioning the overall importance of aortic atherosclerosis in the pathogenesis of cerebrovascular events in the general population. PMID:11809426

Agmon, Yoram; Khandheria, Bijoy K; Meissner, Irene; Schwartz, Gary L; Petterson, Tanya M; O'Fallon, W Michael; Whisnant, Jack P; Wiebers, David O; Seward, James B

2002-02-01

406

A Review of the Significance of Bovine Milk Xanthine Oxidase in the Etiology of Atherosclerosis.  

National Technical Information Service (NTIS)

The hypothesis that xanthine oxidase in homogenized bovine milk is a significant factor in the etiology of atherosclerosis holds that the enzyme is absorbed in the intestinal tract with homogenized milk fat, circulates, is deposited in arterial and myocar...

C. J. Carr J. M. Talbot K. D. Fisher

1975-01-01

407

Susceptibility to Atherosclerosis in Aortas and Coronary Arteries of Swine with von Willebrand's Disease.  

National Technical Information Service (NTIS)

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. ...

T. R. Griggs R. L. Reddick D. Sultzer K. M. Brinkhous

1980-01-01

408

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.

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

2012-01-01

409

High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholesteryl acyltransferase  

Microsoft Academic Search

A subset of patients with high plasma HDL concentrations have enhanced rather than reduced atherosclerosis. We have developed a new transgenic mouse model overexpressing human lecithin-cholesteryl acyltransferase (LCAT) that has elevated HDL and increased diet-induced atherosclerosis. LCAT transgenic mouse HDLs are abnormal in both composition and function. Liver uptake of [3H]cholesteryl ether incorporated in transgenic mouse HDL was reduced by

A M Berard; B Foger; Alan Remaley; Robert Shamburek; Boris L. Vaisman; Glenda Talley; Beverly Paigen; Robert F. Hoyt; Santica Marcovina; H. Bryan Brewer; Fojo S Santamarina

1997-01-01

410

Microarray gene expression profiling reveals antioxidant-like effects of angiotensin II inhibition in atherosclerosis.  

PubMed

Reactive oxygen species (ROS) is a significant feature of atherosclerosis but the impact of ROS on atherogenesis is not clear since antioxidants such as vitamin E have little effect on atherosclerosis development in vivo. To investigate the role of ROS in atherosclerosis, we used ApoE-deficient mice, and compared the treatment effect of the antioxidant vitamin E with that of the angiotensin-converting enzyme (ACE) inhibitor, captopril, because angiotensin II is a major source of ROS in the vasculature. Dihydroethidium (DHE) staining demonstrated that vitamin E and captopril both prevented the atherosclerosis-induced increase in aortic superoxide content. In contrast, seven months of vitamin E treatment retarded the development of atherosclerotic lesions by only 45.8 ± 11.5% whereas captopril reduced the aortic plaque area by 88.1 ± 7.5%. To discriminate between vitamin E-sensitive and -insensitive effects of ACE inhibition, we performed whole genome microarray gene expression profiling. Gene ontology (GO) and immunohistology analyses showed that vitamin E and captopril prevented atherosclerosis-related changes of aortic intima and media genes. However, vitamin E did not reduce the expression of probe sets detecting the aortic recruitment of pro-inflammatory immune cells while immune cell-specific genes were normalized by captopril treatment. Moreover, vitamin E did not prevent the atherosclerosis-dependent down-regulation of perivascular nerve-specific genes, which were preserved in captopril-treated aortas. Taken together, our study detected antioxidant vitamin E-like effects of angiotensin II inhibition in atherosclerosis treatment regarding preservation of aortic intima and media genes. Additional vitamin E-insensitive effects targeting atherosclerosis-enhancing aortic immune cell recruitment and perivascular nerve degeneration could account for the stronger anti-atherogenic activity of ACE inhibition compared to vitamin E. PMID:23801967

Abd Alla, Joshua; El Faramawy, Yasser; Quitterer, Ursula

2013-06-19

411

Serum Asymmetric Dimethylarginine Negatively Correlates with Intima-Media Thickness in Early-Onset Atherosclerosis  

Microsoft Academic Search

Background: Asymmetric dimethylarginine (ADMA) assumes a significant role in atherosclerosis by inhibiting the endothelial nitric oxide synthase (eNOS). Moreover, ADMA inhibits the inducible NOS (iNOS), the isoform that triggers atherosclerosis via peroxynitrite formation. Therefore, we investigated whether ADMA is a risk or protective factor in the atherosclerotic process. Intima-media thickness (IMT) of the common carotid artery, a surrogate for vascular

Judit Zsuga; Janos Török; Mária Tünde Magyar; Attila Valikovics; Rudolf Gesztelyi; Sandor Kéki; Laszló Csiba; Miklos Zsuga; Dániel Bereczki

2007-01-01

412

Antiphospholipid Antibodies and Atherosclerosis: Insights from Systemic Lupus Erythematosus and Primary Antiphospholipid Syndrome  

Microsoft Academic Search

The issue of atherosclerosis in the antiphospholipid syndrome (APS) is receiving considerable attention within and without\\u000a the autoimmune settting. Measurement of arterial intima media thickness (IMT) of is an easy and surrogate means of detecting\\u000a subclinical atherosclerosis. This technique has been applied to patients with systemic lupus erythematosus (SLE) nand primary\\u000a APS in the attempt to unravel a possible association

Paul R. J. Ames; Annamaria Margarita; Jose Delgado Alves

2009-01-01

413

Swimming reduces the severity of atherosclerosis in apolipoprotein E deficient mice by antioxidant effects  

Microsoft Academic Search

Objective: It was shown that aerobic exercise training may protect against the development of atherosclerosis. However, the precise mechanisms are still unknown. We assessed the hypothesis that exercise training reduced the severity of experimental atherosclerosis in apolipoprotein (apo) E-deficient mice by antioxidant effects. Methods: Exercise training (45 min swimming, 3 times\\/week) was conducted on apo E-deficient mice fed a high

Taka-aki Okabe; Kana Shimada; Miki Hattori; Toshinori Murayama; Masayuki Yokode; Toru Kita; Chiharu Kishimoto

2007-01-01

414

Comparison of two diets of varying glycemic index on carotid subclinical atherosclerosis in obese children  

Microsoft Academic Search

Childhood obesity is associated with an increased carotid intima-media thickness (IMT) and stiffness. Increased carotid wall\\u000a thickening and rigidity are considered markers of subclinical atherosclerosis. The aim of the present study was to test the\\u000a effect of two hypocaloric diets of varying glycemic index on weight loss and markers of subclinical atherosclerosis in obese\\u000a children. Seventy consecutive obese children attending

Arcangelo Iannuzzi; Maria Rosaria Licenziati; Maria Vacca; Donata De Marco; Giorgio Cinquegrana; Marco Laccetti; Alessandro Bresciani; Giuseppe Covetti; Gabriella Iannuzzo; Paolo Rubba; Mario Parillo

2009-01-01

415

Atherosclerosis in ApoE-deficient mice progresses independently of the NLRP3 inflammasome  

Microsoft Academic Search

The interleukin-1 (IL-1) family of cytokines has been implicated in the pathogenesis of atherosclerosis in previous studies. The NLRP3 inflammasome has recently emerged as a pivotal regulator of IL-1? maturation and secretion by macrophages. Little is currently known about a possible role for the NLRP3 inflammasome in atherosclerosis progression in vivo. We generated ApoE?\\/? Nlrp3?\\/?, ApoE?\\/? Asc?\\/? and ApoE?\\/? caspase-1?\\/?

P Menu; M Pellegrin; J-F Aubert; K Bouzourene; A Tardivel; L Mazzolai; J Tschopp

2011-01-01

416

integrin deficiency promotes atherosclerosis and pulmonary inflammation in high-fat-fed, hyperlipidemic mice  

Microsoft Academic Search

Hyperlipidemia promotes the chronic inflammatory disease atherosclerosis through poorly understood mechanisms. Atherogenic lipoproteins activate platelets, but it is unknown whether platelets contribute to early inflammatory atherosclerotic lesions. To address the role of platelet aggregation in diet-induced vascular disease, we studied 3 integrin-deficient mice (lacking platelet integrin IIb3 and the widely expressed nonplatelet integrin v3) in two models of atherosclerosis, apolipoprotein

Sherry Weng; Laura Zemany; Kara N. Standley; Deborah V. Novack; Marie La Regina; Carlos Bernal-Mizrachi; Trey Coleman; Clay F. Semenkovich

2003-01-01

417

New frontiers in atherosclerosis prevention and treatment: HDL as a novel therapeutic target  

Microsoft Academic Search

The high-density lipoprotein (HDL) system offers an attractive target for novel therapeutic approaches to prevent or treat atherosclerosis. Clinical preventative studies with HDL modulators, both increasing HDL levels [peroxisome proliferator activator receptor (PPAR) ? agonists] and stimulating turnover [cholesteryl ester transfer protein (CETP) activators] have led to favorable outcomes. Treatment of preexisting atherosclerosis with novel HDL mimetics, i.e., wild-type recombinant

Cesare R Sirtori

2004-01-01

418

A novel mouse model that develops spontaneous arthritis and is predisposed towards atherosclerosis  

PubMed Central

Objectives Patients with rheumatoid arthritis (RA) have a reduced life expectancy due to increased cardiovascular disease. The lack of a suitable animal model resembling both RA and atherosclerosis has hindered studies demonstrating a direct link between systemic inflammation in RA and the development of atherosclerosis. Our objective was to overcome this barrier by generating an animal model (K/BxAg7) that spontaneously develops both RA-like disease and atherosclerosis. Methods Arthritis severity was evaluated using clinical indices and immunohistochemical staining of ankle joint specimens. Aortic atherosclerosis was delineated via Sudan IV staining and immunohistochemical analysis. Serum cholesterol and lipoprotein levels were measured using enzymatic assays. Serum levels of cytokines, chemokines and adipokines were determined by Luminex assays. Results K/BxAg7 mice developed a destructive arthropathy followed by prominent aortic atherosclerosis. These animals also displayed dyslipidaemia, characterised by reduced serum levels of total cholesterol and high-density lipoprotein, and increased low-density lipoprotein (LDL)/vLDL compared with control mice. Further, there were higher levels of circulating inflammatory mediators, such as interleukin-6, sRANKL and CCL5 in atherosclerotic K/BxAg7 mice compared with controls. Treatment with etanercept reduced arthritis and atherosclerosis development in K/BxAg7 mice. Conclusions K/BxAg7 mice recapitulate the same sequence of events occurring in patients with RA, namely an erosive, inflammatory arthritis followed by atherosclerosis. These data suggest that the K/BxAg7 mouse is a novel system for investigating the interplay between systemic inflammation occurring in RA and the development of atherosclerosis.

Rose, Shawn; Eren, Mesut; Murphy, Sheila; Zhang, Heng; Thaxton, Colby Shad; Chowaniec, Jaime; Waters, Emily A; Meade, Thomas J; Vaughan, Douglas E; Perlman, Harris

2013-01-01

419

Decreased Atherosclerosis in Low-Density Lipoprotein Receptor Knockout Mice Transplanted With Abcg1\\/ Bone Marrow  

Microsoft Academic Search

Objective—Recent studies indicate that the ATP-binding cassette transporter ABCG1 can promote cholesterol efflux from macrophages to high-density lipoprotein. This study was designed to assess the in vivo role of macrophage ABCG1 in atherosclerosis. Methods and Results—Bone marrow from Abcg1\\/ mice was transplanted into irradiated Ldlr\\/ recipients, and atherosclerosis was evaluated by aortic root assay after 7 or 11 weeks of

Mollie Ranalletta; Nan Wang; Seongah Han; Laurent Yvan-Charvet; Carrie Welch; Alan R. Tall

2010-01-01

420

Enhanced ABCG1 expression increases atherosclerosis in LDLr-KO mice on a western diet  

Microsoft Academic Search

ABCG1 promotes cholesterol efflux from cells, but ABCG1?\\/? bone marrow transplant into ApoE?\\/? and LDLr?\\/? mice reduces atherosclerosis. To further investigate the role of ABCG1 in atherosclerosis, ABCG1 transgenic mice were crossed with LDLr-KO mice and placed on a high-fat western diet. Increased expression of ABCG1 mRNA was detected in liver (1.8-fold) and macrophages (2.7-fold), and cholesterol efflux from macrophages

Federica Basso; Marcelo J. Amar; Elke M. Wagner; Boris Vaisman; Beverly Paigen; Silvia Santamarina-Fojo; Alan T. Remaley

2006-01-01