atorvastatin Lipitor
The effect of atorvastatin on platelet function in patients with coronary artery disease.

Tekten T, Ceyhan C, Ercan E, Onbasili AO, Turkoglu C.

Adnan Menderes University Medical School, Cardiology Department, Aydin, Turkey. tarkantekten superonline.com

BACKGROUND: Lipid-lowering therapy was shown to have several beneficial effects in patients with coronary artery disease (CAD). AIM: The objective of this study was to investigate the effect of atorvastatin on platelet aggregation in patients with CAD. METHODS: Twenty-five hypercholesterolaemic patients who had angiographically proven CAD and 16 normal subjects were enrolled. All patients received 10 mg/day atorvastatin for two months. Anti-platelet agents were discontinued 15 days prior to blood sampling at the beginning and at the end of the atorvastatin therapy. Aggregometric curves of the platelets in response to ADP, collagen and epinephrine were obtained using the aggregometry (turbidimetric) technique. RESULTS: In patients with CAD, total cholesterol (TC) and LDL cholesterol (LDL-C) basal levels were measured (230 +/- 49 mg/dl, 140 +/- 41 mg/dl, respectively). Following lipid-lowering therapy, TC and LDL-C decreased significantly (p < 0.05). The activation measurements of aggregometric curves decreased significantly compared with basal parameters in response to ADP but not in response to collagen and epinephrine. CONCLUSION: Lipid-lowering therapy with the HMG-CoA reductase inhibitor, atorvastatin, had a marked reduction effect on platelet aggregation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15255464&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Atorvastatin improves diabetic dyslipidemia and increases lipoprotein lipase activity in vivo.

Schneider JG, von Eynatten M, Parhofer KG, Volkmer JE, Schiekofer S, Hamann A, Nawroth PP, Dugi KA.

Department of Internal Medicine I (Endocrinology & Metabolism), University of Heidelberg, Germany. jochen.schneider mailhost-js.de

A major factor contributing to cardiovascular mortality in type 2 diabetes is dyslipidemia, characterized by low HDL cholesterol and high triglycerides, rather than elevated LDL cholesterol. Lipoprotein lipase (LPL) is the rate-limiting enzyme of triglyceride removal from plasma and has been implicated in atherosclerosis. Since treatment with statins significantly reduces cardiovascular morbidity in diabetes, we analyzed the lipid profile and LPL activities in 61 patients with type 2 diabetes before and 8 weeks after initiation of atorvastatin (40 mg) or placebo treatment. Lipid parameters and LPL activity were unchanged under treatment with placebo. Atorvastatin treatment resulted in a 30% reduction of total and a 45% reduction of LDL cholesterol (6.06 +/- 1.39 mmol/L versus 4.14 +/- 1.27 mmol/L and 4.11 +/- 1.13 mmol/L versus 2.27 +/- 0.89 mmol/L, both P < 0.0001). Triglycerides and VLDL cholesterol were also significantly reduced by statin therapy (2.24 +/- 2.11 mmol/L versus 1.82 +/- 1.46 mmol/L and 1.08 +/- 1.56 mmol/L versus 0.67 +/- 0.66 mmol/L, both P < 0.05). HDL cholesterol was not different between the atorvastatin and the placebo group. Compared to baseline, LPL activity was increased by 25% after atorvastatin treatment (213.0 +/- 28.1 nmol/mL/min versus 171.9 +/- 17.7 nmol/mL/min, P < 0.01). Our data demonstrate that atorvastatin induces a significant improvement of diabetic dyslipidemia and a significant increase of LPL activity. Since low LPL activity indicates an increased cardiovascular risk, the statin-mediated increase in LPL activity may help to explain the reduction of CAD in diabetic patients treated with statins. Copyright 2004 Elsevier Ireland Ltd

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15262189&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Impact of Vitamin E supplementation on lipoprotein peroxidation and composition in Type 1 diabetic patients treated with Atorvastatin.

Manuel-Y-Keenoy B, Vinckx M, Vertommen J, Van Gaal L, De Leeuw I.

Metabolic Research Unit, University of Antwerp, Antwerp, Belgium. begona.manuelykeenoy2ua.ac.be

OBJECTIVE: To investigate the impact of Vitamin E on lipids and peroxidation during statin treatment. RESEARCH DESIGN AND METHODS: T1DM patients with high cholesterol received Atorvastatin 20mg with either placebo (group AP, n = 11) or d-alpha-tocopherol 750 IU (group AE, n = 11) daily. They were monitored for blood biochemistry, low-density lipoprotein (LDL) subfractions and lipid peroxidation at inclusion and after 3 and 6 months. RESULTS: Serum cholesterol and triglycerides decreased to the same extent (29 and 21% respectively) in both groups. Serum tocopherol decreased by 18% in AP and increased by 50% in AE (P < 0.0001, between-group comparison by repeated measures ANOVA) but relative to lipids it increased by 15% in AP and by 100% in AE. Copper-induced production of thiobarbituric reactive substances in the LDL + VLDL fraction increased by 18% in AP and did not change in AE (P = 0.02). The lagtime for the production of fluorescent products was prolonged by 13 min only in group AE (P = 0.028). Plasma malondialdehyde decreased by 35% in both groups (P = 0.002) but not when adjusted for lipids. CONCLUSIONS: In T1DM Vitamin E supplements do not affect the lowering of lipids and plasma malondialdehyde achieved by Atorvastatin. They reverse the increase of in vitro peroxidation caused by Atorvastatin but do not achieve the decreases observed in patients not receiving lipid-lowering drugs. These results indicate that the antioxidant effect of Vitamin E is attenuated when given in conjunction with this statin. Copyright 2004 Elsevier Ireland Ltd

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15262194&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Effect of atorvastatin on the expression of CD40 ligand and P-selectin on platelets in patients with hypercholesterolemia.

Hwang YS, Tsai WC, Lu YH, Lin CC, Chen YF.

Division of Cardiology, Department of Medicine, Kaohsiung Medical University, Taiwan. yshwangr ms19.hinet.net

The effects of atorvastatin on levels of the CD40 ligand (CD40L or CD154) and P-selectin on platelets were investigated in patients with hypercholesterolemia. The major finding was that short-term atorvastatin treatment (8 weeks) in a group of hypercholesterolemic patients resulted in significant suppression of CD40L and P-selectin expression. Moreover, there was a significant correlation between the magnitude of CD40L downregulation and that of very low-density lipoprotein cholesterol, the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol, and triglycerides. In hypercholesterolemic patients, in addition to its effects on decreasing cholesterol, atorvastatin can intervene in the interaction of CD40-CD40L and the expression of P-selectin on platelets. Thus, interference of CD40-CD40L can be recognized as an integral part of the anti-inflammatory activity of atorvastatin in hypercholesterolemia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15276107&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Antioxidant effects of statins via S-nitrosylation and activation of thioredoxin in endothelial cells: a novel vasculoprotective function of statins.

Haendeler J, Hoffmann J, Zeiher AM, Dimmeler S.

Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany.

BACKGROUND: HMG-CoA reductase inhibitors (statins) are lipid-lowering drugs that also exert pleiotropic vasculoprotective effects via activation of the endothelial NO synthesis. NO induces S-nitrosylation of target proteins. S-Nitrosylation of the antioxidant enzyme thioredoxin was recently shown to enhance its activity, thereby reducing intracellular reactive oxygen species. Therefore, we investigated whether statins may exert an antioxidant activity in endothelial cells via S-nitrosylation of thioredoxin. METHODS AND RESULTS: Statins dose- and time-dependently increased the overall level of S-nitrosylated proteins in endothelial cells (atorvastatin 0.1 micromol/L, 206+/-30% increase; simvastatin 1 micromol/L, 214+/-19% increase; mevastatin 1 micromol/L, 191+/-10% increase). The increased S-nitrosylation was blocked by an NO-synthase inhibitor and mevalonate. Moreover, S-nitrosylation of thioredoxin was also significantly augmented after atorvastatin treatment. The atorvastatin-mediated increase in S-nitrosylation was associated with an enhanced enzymatic activity of thioredoxin (atorvastatin, 157+/-9% increase). This resulted in a significant reduction of intracellular reactive oxygen species within the endothelial cells. In contrast, in endothelial cells overexpressing a thioredoxin construct in which the S-nitrosylation acceptor amino acid cysteine 69 was replaced by serine [TRX(C69S)], atorvastatin did not activate the redox-regulatory activity of thioredoxin. Moreover, overexpression of the non-nitrosylatable thioredoxin TRX(C69S) abolished atorvastatin-mediated reduction of reactive oxygen species. CONCLUSIONS: Here, we demonstrate a novel antioxidant mechanism by which statins reduce reactive oxygen species in endothelial cells. Statin-mediated S-nitrosylation of thioredoxin enhanced the enzymatic activity of thioredoxin, resulting in a significant reduction in intracellular reactive oxygen species.

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atorvastatin Lipitor
Circulating monocytes and plasma inflammatory biomarkers in active Crohn's disease: elevated oxidized low-density lipoprotein and the anti-inflammatory effect of atorvastatin.

Grip O, Janciauskiene S, Lindgren S.

Gastroenterology and Hepatology Division, Department of Medicine, Lund University, Malmo University Hospital, Malmo, Sweden. olof.grip medforsk.mas.lu.se

We investigated inflammatory biomarkers in plasma and in circulating monocytes obtained from patients with Crohn's disease and healthy individuals. Additionally, we assessed the effects of atorvastatin, 10 microM, ex vivo on monocytes cultured for 18 hours from the same subjects. Plasma and blood monocytes from eight patients with active Crohn's disease and eight healthy individuals were analyzed by enzyme-linked immunosorbent and electrophoretic mobility assays. Patients with active Crohn's disease had increased plasma levels of tumor necrosis factor (TNF)-alpha (7.7-fold;p < 0.05), monocyte chemoattractant protein (MCP)-1 (1.3-fold; p < 0.05), and oxidized low density lipoprotein (oxLDL) (1.2-fold; p < 0.05). Monocytes from patients with Crohn's disease showed enhanced secretion of MCP-1 (4.8-fold; p < 0.05) and a markedly suppressed secretion of macrophage migration inhibitory factor (MIF) (93%; p < 0.001). Transcriptional activation of nuclear factor-kappaB did not differ between the groups. Treating monocytes with atorvastatin resulted in the suppression of MCP-1 (42%; p < 0.05) and TNF-alpha (45%; p < 0.05) secretion. These results show increased levels of certain proinflammatory biomarkers, including oxLDL, in plasma and indicate that peripheral blood monocytes in active Crohn's disease are sensitized to chemotaxis. Treatment with atorvastatin may be a potential strategy to reduce oxLDL and inhibit monocyte migration to inflamed tissue, thus attenuating the inflammatory response.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15290911&dopt=Abstract atorvastatin Lipitor