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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite meaningful progress in the identification of risk factors and the development of highly effective clinical tools, deaths from cardiovascular disease continue to increase worldwide. Sparked by an obesity epidemic, the metabolic syndrome and the rising incidence of type 2 diabetes have led to an upsurge of cardiovascular risk. Although pharmacologic treatments with the statin class of drugs have reduced cholesterol levels and lowered mortality rates, several large controlled clinical trials, including the Scandinavian Simvastatin Survival Study, the Cholesterol and Recurrent Events trial, the Air Force/Texas Coronary Atherosclerosis Prevention studies, and Long-term Intervention with Pravastatin in Ischemic Disease study, have indicated that cardiovascular events continue to occur in two thirds of all patients. Follow-up studies, such as the Heart Protection Study and the Pravastatin or Atorvastatin Evaluation and Infection Therapy/Thrombolysis In Myocardial Infarction-22 trials, reinforced these earlier results. Although therapy with gemfibrozil, a fibric acid derivative, showed reduced occurrence of cardiovascular events in the Helsinki Heart Study and the Veterans Affairs HDL Intervention Trial, results of other studies, e.g., the Bezafibrate Intervention Program and the Diabetes Atherosclerosis Intervention study, showed less encouraging results. Although lifestyle modifications, such as improved diet and increased exercise levels, benefit general health and the metabolic syndrome and insulin resistance in particular, most people continue to resist changes in their daily routines. Thus, physicians must continue to educate their patients regarding an optimal balance of drug therapy and personal behavior.
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PMID:The forgotten majority: unfinished business in cardiovascular risk reduction. 1619 35

We hypothesized that a reduction in atherogenic malondialdehyde-modified low-density lipoprotein (MDA-LDL) levels, which may antagonize the action of atheroprotective high-density lipoprotein cholesterol, leads to coronary plaque regression. This study investigated the effects of pravastatin on the serum levels of MDA-LDL and coronary atherosclerosis. In a 6-month prospective study, 75 patients with stable coronary artery disease were randomly assigned to a pravastatin-treatment group (n = 52) or a control group (n = 23). Volumetric analyses were performed in matched coronary artery segments by 3-dimensional intravascular ultrasound. Pravastatin therapy for 6 months resulted in a decrease in coronary plaque volume (14.4%, p <0.0001) and a corresponding reduction in serum MDA-LDL levels (12.7%, p = 0.0001). In the pravastatin treatment group, the percentage of change in plaque volume correlated with changes in the MDA-LDL and high-density lipoprotein cholesterol levels (r = 0.52 and -0.55, respectively, p <0.0001) but not with the changes in any other lipid levels. Multivariate regression analysis revealed that a reduced MDA-LDL level is an independent predictor of plaque regression, as was an increase in high-density lipoprotein cholesterol. In conclusion, these results suggest that the reduction in the MDA-LDL levels induced by pravastatin may serve as a novel marker of coronary atherosclerosis regression.
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PMID:Effect of pravastatin on malondialdehyde-modified low-density lipoprotein levels and coronary plaque regression as determined by three-dimensional intravascular ultrasound. 1621 43

Macrophages play a part in pathogenesis of atherosclerosis, oxidizing LDL-cholesterol and transforming themselves in foam cells and producing free radicals of oxygen that may also oxidize LDL-cholesterol. HMG-CoA reductase inhibitors are very efficient in long-term control of atherogenesis acting by different mechanisms not fully established. Thus, we investigated the in vitro influence of pravastatin on phagocytosis and hydrogen peroxide production by monocytes of healthy individuals. Phagocytosis of Saccharomyces erevisiae by peripheral blood monocytes of 20 healthy individuals was assessed in the absence or presence of pravastatin. Hydrogen peroxide production was assessed based on the horseradish peroxidase-dependent oxidation of phenol red method. Pravastatin had no influence on phagocytosis through scavenger receptors, while it decreased by 20% the mean+/-SD phagocytic index of monocytes through complement receptors, from 141+/-77 to 113+/-56 (p=0.017), due to a decrease in the number of particles ingested by monocytes, from 2.1+/-0.5 to 1.7+/-0.3 (p=0.003). This statin also decreased the baseline production of hydrogen peroxide, by 7.7%, from 0.098+/-0.013 to 0.091+/-0.013 (OD by 2x10(5) monocytes per hour) (p=0.025). Pravastatin was able to decrease the phagocytosis through complement receptors and caused a decrease in the production of hydrogen peroxide by monocytes. It is possible this statin may directly inhibit the development of atherosclerotic plaque and its instability dependent on phagocytosis and the presence of reactive species of oxygen.
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PMID:Effects of pravastatin on the in vitro phagocytic function and hydrogen peroxide production by monocytes of healthy individuals. 1633 13

The pathophysiological features of nephrosclerosis may be analogous to those of atherosclerosis, which is intimately related to lipid metabolism. Thus, we examined whether a lipid-lowering agent, pravastatin, would ameliorate renal damage in hypertensive model animals. Salt-loaded Dahl salt-sensitive (S) rats were given pravastatin (2 mg/ml in drinking water) for 5 weeks. Pravastatin decreased systolic blood pressure. Although pravastatin did not influence the serum total, high-density, or low-density lipoprotein cholesterol, serum triglycerides were decreased. Pravastatin decreased urinary protein excretion and ameliorated histopathological damage in salt-loaded Dahl S rats. Increased urinary excretion of 8-iso-prostagaldin F2alpha and 8-hydroxy-2'-deoxyguanosine and renal superoxide overproduction and decreased reduced glutathione in the renal parenchyma were ameliorated with pravastatin in Dahl S rats fed a high salt diet. Therefore, pravastatin inhibited the progression of renal injury in salt-loaded Dahl S rats, through its antioxidant as well as its depressor effects.
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PMID:Renoprotective effect of pravastatin in salt-loaded Dahl salt-sensitive rats. 1667 41

Gamma tocopherol (gamma-T) is a recognized peroxynitrite scavenger, reputedly metabolized via the cytochrome P450 3A4 (CYP3A4). In this study, we assessed whether equipotent LDL-lowering doses of statins with or without inhibitory activity on CYP3A4 differently affect gamma-T metabolism. Patients with ATP III criteria for statin use (n=35) were randomly allocated to treatment with simvastatin 20mg/day or pravastatin 40 mg/day. Plasma lipids, alpha-tocopherol (alpha-T), gamma-T as well as the urinary excretion of the gamma-T metabolite 2,7,8-trimethyl-2-(2'carboxyethyl)-6-hydroxychroman (gamma-CEHC), were determined at baseline and after 6 weeks of treatment. Pravastatin and simvastatin equally reduced LDL-C (-42.8+/-2.9 and -42.1+/-3.0%) and alpha-T levels (-17.5+/-4.2 and -12.2+/-4.1%), and increased the alpha-T/LDL-C ratios (51.4+/-14.6 and 60.4+/-15%). Conversely, pravastatin did not affect whereas simvastatin significantly augmented plasma gamma-T levels (22+/-7.9%, p=0.009, between groups p=0.0045). Moreover, the gamma-T/LDL-C ratio increased significantly more with simvastatin than with pravastatin (124+/-23 versus 61.3+/-22.1%, p=0.05 between groups). In addition, pravastatin but not simvastatin increased the urinary excretion of gamma-CEHC (34.3+/-17.3%, p=0.056; between groups p=0.046). In conclusion, simvastatin and pravastatin produced distinct effects on gamma-T metabolism, presumably as a result of different statin-CYP interactions.
Atherosclerosis 2007 Jul
PMID:A new compound-specific pleiotropic effect of statins: modification of plasma gamma-tocopherol levels. 1686 Aug 8

Circulating bone marrow-derived vascular progenitor cells contribute to angiogenesis, atherosclerosis, and the response to vascular injury. These vascular progenitor cells consist of two cell groups, endothelial progenitor cells (EPCs) and smooth muscle progenitor cells (SMPCs). Although HMG-CoA reductase inhibitors (statins) have been reported to inhibit atherosclerosis partially by increased EPCs, the effects of statins on SMPCs are unclear. Therefore, we investigated the relationship between EPCs and SMPCs and whether pravastatin has atheroprotective effects on SMPCs. Peripheral mononuclear cells (MNCs) were isolated and cultured on fibronectin-coated dishes in SMPC medium. MNCs were stained with acetylated low density lipoprotein and lectin, or alpha-smooth muscle actin, and cell numbers were counted. mRNA expression and vascular endothelial growth factor (VEGF) protein synthesis of MNCs were evaluated. Pravastatin significantly increased the number of EPC and decreased the number of SMPC. mRNA expression of VEGF, endothelial nitric oxide synthase, VEGF receptor-2 (KDR), and Akt were up-regulated, and VEGF secretion was increased by pravastatin. The present study demonstrated that pravastatin has promotive effects on the differentiation from MNCs to EPC cells, while inhibitory effects to SMPC cells. Our findings suggest a previously unreported mechanism of the effect of statin therapy on vascular progenitor cells.
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PMID:The effects of HMG-CoA reductase inhibitor on vascular progenitor cells. 1689 63

Reduced incidence of type-2 diabetes has been shown in patients treated with pravastatin. Adiponectin can exhibit beneficial effects on glucose metabolism. We investigated whether pravastatin could improve glucose tolerance associated with increasing adiponectin levels in patients with impaired glucose tolerance (IGT). This study consisted of 40 coronary artery disease (CAD) patients with IGT assessed by oral glucose tolerance test (OGTT). Patients were randomized to receive pravastatin (n=20) or no lipid-lowering medications (control group, n=20) for 6 months, after which OGTT was repeated and adiponectin levels were measured. Pravastatin treatment significantly decreased levels of total cholesterol (16%), low-density lipoprotein cholesterol (23%) and high-sensitivity C-reactive protein (37%) (p<0.01, respectively). At 2h in OGTT, pravastatin significantly improved hyperglycemia (-14%) and hyperinsulinemia (-23%). Pravastatin treatment significantly elevated plasma adiponectin levels (35%; p<0.001) but not in the control group. The glucose reduction at 2h post-OGTT was significantly associated with increased levels of adiponectin (r=-0.462; p=0.003). Pravastatin treatment is an independent predictor for improvement of post-loaded hyperglycemia (odds ratio; 5.7; 95% confidence interval 1.7-19.3; p=0.003) and achieved beneficial conversion from IGT to normal glucose tolerance (40%; p=0.03). Pravastatin exhibits beneficial effects on glucose metabolism especially in the postprandial state associated with increasing plasma adiponectin levels in CAD patients with IGT.
Atherosclerosis 2007 Oct
PMID:Pravastatin improved glucose metabolism associated with increasing plasma adiponectin in patients with impaired glucose tolerance and coronary artery disease. 1711 29

The purpose of this double-blind, randomized, placebo-controlled trial was to determine the long-term effects of pravastatin and fosinopril treatment on peripheral endothelial function in subjects with albuminuria. Subjects (mean age 51 years, 63% male) were randomized to pravastatin 40 mg or matching placebo and to fosinopril 20mg or matching placebo. Using high resolution ultrasound, flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) was assessed at baseline and after 4 years of treatment in a total of 276 subjects. At baseline, mean+/-standard error FMD was 4.73+/-0.49% and NID was 10.86+/-0.67%. Pravastatin significantly reduced total cholesterol and LDL cholesterol (p<0.01) and randomization to pravastatin was associated with a non-significant improvement of 18.9% in FMD (+0.80+/-0.95, p=0.09), without a significant change in NID. Interestingly, pravastatin significantly increased FMD by 34.9% in men (+1.23, p=0.04), but only 1.1% in women (+0.06, p=0.95). Fosinopril was not associated with a change in FMD or NID despite significantly decreasing urinary albumin excretion, systolic and diastolic blood pressure (all p<0.01). In conclusion, after 4 years of follow-up, pravastatin treatment tended to increase FMD and this effect was predominantly present in men. Fosinopril treatment did not modify FMD during long-term follow-up.
Atherosclerosis 2008 Jan
PMID:Long-term effects of pravastatin and fosinopril on peripheral endothelial function in albuminuric subjects. 1714 Dec 45

Angiotensin II is a potent vasoconstrictor and may also contribute to the progression of atherosclerosis. In atheromatous lesions located in human coronary and carotid arteries, angiotensin-converting enzyme and angiotensin II levels are significantly increased. Angiotensin II is known to have proinflammatory actions in vascular tissues, inducing inflammatory cytokines and oxidative stress. In particular, angiotensin II activates the potent cytoplasmic transcription factor nuclear factor-kappaB, which regulates leukocyte adhesion molecules, tumor necrosis factor (TNF)-alpha, monocyte chemotactic protein (MCP)-1, and interleukin (IL)-6, and contributes to the recruitment of circulating mononuclear leukocytes to the arterial intima. Olmesartan medoxomil has one of the highest degrees of antihypertensive efficacy among the angiotensin II type 1 receptor antagonists. In the EUTOPIA (EUropean Trial on Olmesartan and Pravastatin in Inflammation and Atherosclerosis) trial, olmesartan medoxomil significantly reduced serum levels of high-sensitivity C-reactive protein, high-sensitivity TNFalpha, IL-6, and MCP-1, all of which are involved in promoting atherosclerosis. In a monkey atherosclerotic model, a 3-D intravascular ultrasound analysis of aortas showed that serum levels of MCP-1 and the degree of intimal hyperplasia were significantly lower after treatment with olmesartan medoxomil than before treatment. In VIOS (Vascular Improvement with Olmesartan Medoxomil Study), treatment with olmesartan medoxomil for 1 year, significantly reduced the wall-to-lumen ratio in arteries, whereas atenolol did not. Thus, olmesartan medoxomil, which rapidly reduces inflammatory markers, may have a beneficial antiatherosclerotic effect.
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PMID:Effect of olmesartan medoxomil on atherosclerosis: clinical implications of the emerging evidence. 1719 25

In the West of Scotland Coronary Prevention Study (WOSCOPS), treatment of hypercholesterolemic men with pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, reduced their likelihood to progress to diabetes mellitus by 30%. However, the mechanism of this effect of pravastatin has not been investigated. In the current study, we examined the effect of pravastatin on the development of diabetes in obese diabetic mice, and on the insulin-induced glucose uptake and adiponectin production. Pravastatin treatment attenuated the development of diabetes in db/db and high fat/high sucrose diet-fed C57BL/6J mice. An in vivo glucose transport assay showed that pravastatin upregulated glucose uptake in adipose tissue. Insulin-stimulated glucose uptake was enhanced in primary adipocytes isolated from pravastatin-treated mice. Pravastatin treatment increased adiponectin production in 3T3-L1 adipocytes. Plasma adiponectin levels were significantly increased in pravastatin-treated mice. Analyses of plasma samples from the WOSCOPS biobank indicated a significant increase of plasma adiponectin levels with pravastatin treatment (placebo -0.28+/-0.34 microg/ml versus pravastatin +1.47+/-0.33 microg/ml, p=0.0003). Taken together, our findings suggest that pravastatin may have beneficial effects on adipose tissue, which may partly explain the reduction of the development of diabetes by pravastatin treatment.
Atherosclerosis 2008 Jan
PMID:Effect of pravastatin on the development of diabetes and adiponectin production. 1739 75


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