UMLS:C0004153 - FACTA Search

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

Visfatin is a novel adipokine involved in the process of atherosclerosis. We assessed the effect of rosuvastatin on plasma visfatin levels in patients with primary hyperlipidemia. Eighty hyperlipidemic patients without evidence of cardiovascular disease were randomized to receive either rosuvastatin 10 mg/day or therapeutic lifestyle changes intervention. Plasma visfatin levels were determined at baseline and after 12-weeks post-randomization. Rosuvastatin induced a significant decrease in plasma visfatin levels (17.1+/-2.1 versus 15.5+/-2.0 ng/ml, P=0.03). This effect correlated with baseline visfatin levels (r=0.51, P<0.01) and was independent of any lipid-lowering actions of rosuvastatin.
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PMID:Effect of rosuvastatin treatment on plasma visfatin levels in patients with primary hyperlipidemia. 1793 20

Statin-treatment of fructose-fed/insulin resistant hamsters was recently shown to ameliorate metabolic dyslipidemia and hepatic VLDL overproduction. Here, we provide evidence that rosuvastatin treatment of insulin resistant hamsters can induce improvements in hepatic and whole body insulin sensitivity. Treatment with 10 mg/kg/day rosuvastatin for 10 days significantly reduced fasting insulin (-59%) and triglyceride (-50%) levels in fructose-fed hamsters (p<0.05). Following an intraperitoneal (IP) glucose challenge, rosuvastatin-treated hamsters exhibited enhanced glucose clearance compared to untreated hamsters maintained on the high-fructose diet (area under curve (AUC)=1772+/-223 mM min vs. 2413+/-253 mM min, respectively; p<0.002) with a significant reduction in 2h post-challenge glucose (n=5, p<0.02). Rosuvastatin-treatment also significantly improved sensitivity to an IP insulin challenge (AUC=314+/-39 mM min vs. 195+/-22 mM min for rosuvastatin-treated and fructose-fed hamsters, respectively; p<0.04, n=3). At the molecular level, significant increases in tyrosine-phosphorylation of the hepatic insulin receptor and IRS-1 were observed for rosuvastatin-treated hamsters (+37% and +58%, respectively) compared to fructose-fed controls following an intravenous (IV) bolus of insulin (p<0.05). Increases in insulin receptor and IRS-1 phosphorylation were also observed in muscle and adipose tissue. Analysis of hepatic Akt phosphorylation and mass revealed a small (25%) increase in serine phosphorylation of Akt with no significant change in Akt mass, although serine-phosphorylation and mass of Akt2 were significantly increased (+32%, p=0.03, and +42%, p=0.01, respectively). Interestingly, expression of PTP-1B, a key negative regulator of insulin signaling, showed a non-significant trend toward reduction in liver and was significantly reduced in adipose tissue (-20% and -37%, respectively). Taken together, these data suggest that statin-treatment increases whole body and peripheral tissue insulin sensitivity via improved cellular insulin signal transduction.
Atherosclerosis 2008 May
PMID:Effect of rosuvastatin on insulin sensitivity in an animal model of insulin resistance: evidence for statin-induced hepatic insulin sensitization. 1809 97

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, exert various beneficial effects independent of serum cholesterol reduction; among others is antioxidative action. Human promyelocytic cells (HL-60) were used to examine the effect of the statin rosuvastatin on reactive oxygen species-induced DNA damage, formation of oxidative stress and expression of glutathione metabolising enzymes. Rosuvastatin from 10nM significantly reduced DNA damage induced by phorbol 12-myristate 13-acetate (PMA) or by hydrogen peroxide, as assessed by the comet assay. PMA-provoked formation of reactive oxygen species, measured by flow cytometric measurement, was also prevented by rosuvastatin. Pre-incubation of cells with rosuvastatin revealed a protective effect of the statin even after its removal from the incubation medium. Total glutathione in cells treated with PMA, with and without co-incubation with rosuvastatin, was increased significantly in cells incubated with rosuvastatin alone. The quantification of the mRNA and activity of glutathione synthesizing enzymes by PCR showed a significant upregulation of gamma-glutamylcysteine synthetase. In conclusion, rosuvastatin exerts antioxidative effects, which are also capable of preventing DNA damage. These effects seem to be independent of HMG-CoA reductase inhibition and involve the induction of the expression of antioxidant defense enzymes.
Atherosclerosis 2008 Aug
PMID:Rosuvastatin protects against oxidative stress and DNA damage in vitro via upregulation of glutathione synthesis. 1815 58

Calcific aortic stenosis (AS) is a progressive disease that has, until recently, been considered to be a degenerative and unmodifiable process induced by long-lasting mechanical stress. However, histopathologic studies have now demonstrated that the development and progression of calcific AS is based on an active process, sharing a number of similarities with atherosclerosis. Inflammation, lipid infiltration, dystrophic calcification, ossification, platelet deposition and endothelial dysfunction have been observed in both diseases. In addition, several studies have suggested that AS and atherosclerosis share a number of risk factors, such as hypercholesterolemia, elevated lipoprotein (a), smoking, hypertension and diabetes. These findings suggest that statin therapy could be beneficial in AS by its lipid-lowering and/or anti-inflammatory effects, as is the case in atherosclerosis. Although this concept has been supported by experimental work and by four retrospective clinical studies observing significantly slower rates of hemodynamic progression in statin-treated patients, a prospective randomized trial (Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression [SALTIRE]; 80mg of atorvastatin vs placebo) yielded a negative result. In contrast to the retrospective analyses, according to the study protocol, patients with hyperlipidemia had to be excluded in this trial. A recent prospective study (Rosuvastatin Affecting Aortic Valve Endothelium [RAAVE]) treating hypercholesteremic patients with rosuvastatin, found a significantly slower rate of progression in these patients compared with patients with normal cholesterol levels who were left untreated, suggesting that statin therapy may only be beneficial in patients with hyperlipidemia. Lipid-lowering therapy with statins can, therefore, currently only be recommended in this subgroup of patients with AS.
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PMID:Aortic sclerosis, aortic stenosis and lipid-lowering therapy. 1832 97

The HMG-CoA reductase inhibitor (statin) rosuvastatin (Crestor) is widely available for use in the management of dyslipidemia, and was recently approved in the US to slow the progression of atherosclerosis as part of a strategy to lower low-density lipoprotein-cholesterol (LDL-C) and total cholesterol (TC) to target levels. Rosuvastatin has greater lipid-lowering efficacy than any of the other currently available statins, and significantly more patients receiving rosuvastatin than other statins achieve LDL-C goals. Rosuvastatin delayed the progression of carotid atherosclerosis in patients with subclinical carotid atherosclerosis, moderately elevated cholesterol levels, and a low risk of cardiovascular disease in a primary prevention trial (METEOR). The results of METEOR suggest a possible role for the earlier use of rosuvastatin in primary prevention, although more data are needed from trials examining the effects of the drug on cardiovascular endpoints. Significant regression of atherosclerosis was seen with rosuvastatin 40 mg/day in patients with established coronary heart disease (CHD) in the ASTEROID trial, supporting the use of intensive lipid lowering in secondary prevention patients (although it should be noted that it has not yet been established that atherosclerotic regression translates into improved cardiovascular outcomes). Rosuvastatin is generally well tolerated, with a similar tolerability profile to that of other currently available statins. Thus, rosuvastatin is an important lipid-lowering treatment option that has been shown to cause regression of atherosclerosis in secondary prevention patients, and has a potential future role in delaying atherosclerosis in primary prevention patients.
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PMID:Rosuvastatin: a review of its effect on atherosclerosis. 1842 95

Atherothrombosis of the coronary and cerebral vessels is understood to be a disorder of inflammation and innate immunity, as well as a disorder of lipid accumulation. From a vascular biology perspective, the processes of cellular adhesion, monocyte and macrophage attachment, and transmigration of immune cells across the endothelium are crucial steps in early atherogenesis and in the later stages of mature plaque rupture, particularly the transition of unstable plaque at the time of acute thrombosis. There is abundant clinical evidence demonstrating that many biomarkers of inflammation are elevated years in advance of first ever myocardial infarction (MI) or thrombotic stroke and that these same biomarkers are highly predictive of recurrent MI, recurrent stroke, diabetes, and cardiovascular death. In daily practice, the inflammatory biomarker in widest use is high-sensitivity C-reactive protein (hsCRP); when interpreted within the context of usual risk factors, levels of hsCRP <1, 1 to 3, and >3 mg/l denote lower, average, and higher relative risk for future vascular events. Risk-prediction models that incorporate hsCRP, such as the Reynolds Risk Score, have been developed that improve risk classification and the accuracy for global risk prediction, particularly for those deemed at "intermediate risk" by usual algorithms, such as the Framingham Risk Score. With regard to cerebral vessels, increased biomarkers of inflammation, including hsCRP, have been associated with increased stroke risk as well as an increased rate of atherosclerosis progression in the carotid vessels. Although the proportion of variation in hsCRP explained by genetic factors may be as large as 20% to 40%, diet, exercise, and smoking cessation remain critical tools for risk reduction and CRP reduction. Statin therapy reduces hsCRP in a largely low-density lipoprotein (LDL)-independent manner, and the "anti-inflammatory" properties of these agents have been suggested as a potential mechanism beyond LDL reduction for the efficacy of these agents. The ongoing multinational Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial of 17,802 initially healthy men and women with low levels of LDL cholesterol but increased levels of hsCRP will help to define whether vascular protection can be achieved with statin therapy, even in the absence of hyperlipidemia. Targeted anti-inflammatory therapies are being developed that may provide a direct method of translating the biology of inflammation into new clinical treatments across multiple vascular beds. This article summarizes data supporting a role for inflammation in cardiovascular disease and offers the possibility that other disorders characterized by inflammation, such as periodontal disease, may have an indirect role by influencing the risk, manifestation, and progression of vascular events.
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PMID:Inflammation, C-reactive protein, and atherothrombosis. 1867 9

Statins enhance incorporation of bone marrow-derived cells into experimental neointimal lesions. However, the contribution of progenitor cells to progression of spontaneous atherosclerotic plaques, and the possible modulatory role of statins in this process, remain poorly understood. We compared the effects of rosuvastatin (1 and 10mg/kg BW) and pravastatin (10mg/kg) on progenitor cell mobilisation, recruitment into atherosclerotic plaques, and lesion growth. Statins were administered over 8 weeks to apolipoprotein E knockout mice on atherogenic diet. In addition, mice were lethally irradiated, followed by transplantation of bone marrow from LacZ transgenic mice. Rosuvastatin reduced lesion area and intima-to-media ratio at the brachiocephalic artery compared to vehicle, while both parameters were not significantly altered by pravastatin. Rosuvastatin also augmented endothelialisation (P<0.05) and reduced the smooth muscle cells (SMC) content (P=0.042) of lesions. Numbers of c-kit, sca-1 and flk-1, sca-1 double-positive progenitor cells were significantly increased in rosuvastatin compared to control-treated mice, both in the bone marrow and the peripheral blood. Similarly, the number of spleen-derived acLDL, lectin double-positive progenitor cells (P=0.001) and colony-forming units (P=0.0104) was significantly increased in mice treated with rosuvastatin compared to vehicle alone. In the bone marrow, increased Akt and p42/44 MAP kinase phosphorylation and upregulated SDF1alpha mRNA expression were observed. Importantly, rosuvastatin treatment also increased the plasma levels of c-kit ligand (P=0.003), and the number of c-kit-positive cells within atherosclerotic lesions (P=0.041). Our findings suggest that rosuvastatin reduces the size of atherosclerotic plaques, and this effect appears to involve progenitor cell mobilisation and recruitment into vascular lesions.
Atherosclerosis 2009 Jul
PMID:Rosuvastatin reduces atherosclerotic lesions and promotes progenitor cell mobilisation and recruitment in apolipoprotein E knockout mice. 1911 32

Atorvastatin and rosuvastatin at maximal doses are both highly effective in lowering low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels. Rosuvastatin has been shown to be more effective than atorvastatin in lowering LDL-C, small dense LDL-C and in raising high-density lipoprotein (HDL) and its subclasses. Intestinal lipoproteins containing apolipoprotein (apo) B-48 are also thought to be atherogenic particles. Our purpose in this study was to compare the effects of daily oral doses of atorvastatin 80 mg/day and rosuvastatin 40 mg/day over a 6-week period on serum apo B-48 (a marker of intestinal lipoproteins) and remnant lipoprotein cholesterol (RemL-C) levels (a marker of partially metabolized lipoproteins of both intestinal and liver origin), using novel direct assays in 270 hyperlipidemic men and women. Both atorvastatin and rosuvastatin caused significant (p<0.0001) and similar median decreases in TG (-33.0%, -27.6%), RemL-C (-58.7%, -61.5%), and apoB-48 (-37.5%, -32.1%) as compared to baseline. Our findings utilizing a specific immunoassay and a fairly large number of subjects extend prior studies indicating that statins significantly lower apolipoprotein B containing lipoproteins of both intestinal and liver origin.
Atherosclerosis 2009 Jul
PMID:Effects of intensive atorvastatin and rosuvastatin treatment on apolipoprotein B-48 and remnant lipoprotein cholesterol levels. 1920 May 42

Rosuvastatin is a synthetic statin that represents an advance in the pharmacologic and clinical properties of statins. Relative to other statins, rosuvastatin possesses a greater number of binding interactions with HMG-CoA reductase and has a high affinity for the active site of the enzyme. As with other statins, serious adverse effects with rosuvastatin therapy are uncommon and primarily involve effects on the liver and skeletal muscle. The risk increases with increasing dosages and coadministration with other drugs interacting with the same metabolic pathway. The degree of LDL reduction is important to achieve the treatment goals suggested by international guidelines. Among the most potent statins, rosuvastatin is capable of getting the majority of patients to their LDL cholesterol goals. In addition, rosuvastatin has been found effective in reducing small-dense LDL, C-reactive protein and in increasing HDL cholesterol levels. Controlled clinical trials using vascular end-points have been performed. In particular, a study demonstrated that rosuvastatin therapy could slow progression and/or cause regression of carotid intima-media thickness over 2 years in middle-aged individuals with a low Framingham risk score (FRS) and mild to moderate subclinical atherosclerosis. A primary prevention study (JUPITER) was stopped before the programmed end of the study, because of excess benefit for high-risk individuals receiving rosuvastatin treatment. It is suggested that pronounced LDL reduction, in association with significant HDL cholesterol increase, are the bases of a marked preventive action of rosuvastatin. The results from JUPITER support the use of rosuvastatin for primary cardiovascular prevention, in overweight men and women, with near to normal LDL cholesterol and high CRP. There is now evidence of benefit from rosuvastatin treatment for a wide segment of the general population at intermediate cardiovascular risk. In absolute numbers, this segment represents the main source of cardiovascular events: on the basis of JUPITER results, it is expected that treatment target and potential candidates to statin therapy will be reevaluated and redefined.
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PMID:Efficacy and safety of rosuvastatin in the management of dyslipidemia. 1943 57

The progression of atherosclerosis following coronary artery bypass graft (CABG) surgery results in the need for re-vascularisation therapy in a significant proportion of patients. It is well recognised that this risk can be lowered by controlling the level of low-density lipid cholesterol (LDL-C) which can be achieved easily and safely with the use of statins. The choice of which is the best statin in post-CABG patients remains unclear. It has been shown that for milligram-equivalent doses, rosuvastatin provides the greatest LDL-C reduction and greatest number of patients achieving LDL-C targets in comparison with simvastatin and atorvastatin. Rosuvastatin's superiority over other statins in allowing patients to reach LDL-C targets has been maintained in 'real-world' observational studies. Rosuvastatin has also been shown to increase high-density lipid cholesterol (HDL-C) by greater proportions in comparison with other statins, providing increased anti-atherogenic effects. There are several statins currently available, some of which are now generic. However, the empirical use of generic statins does not necessarily translate into a cost-effective treatment option. This article reviews the rationale for lipid-lowering therapy in patients following CABG. We also look objectively at which is the best statin for use in the post-CABG patient, discussing effectiveness, cost and tolerability.
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PMID:Which is the best statin for the postoperative coronary artery bypass graft patient? 1952 49

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