Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Statins are believed to exert beneficial effects against cardiovascular disease beyond correction of dyslipidemia. There are however still very sparse data on how individual statins interact with the production of vasoactive eicosanoids and nitric oxide (NO) in human vascular endothelial cells. Here we have determined how fluvastatin affects the mRNA expression of genes associated with vascular reactivity as well as the formation of two major vasodilators, prostacyclin (PGI2) and NO, in human endothelial cells. Also, the influence of fluvastatin on arterial resistance was assessed in isolated small arteries. We show that the promoter activity of prostacyclin synthase (PTGIS), the mRNA expression of PTGIS and endothelial nitric oxide synthase (eNOS), and the production of PGI2 and NO are significantly induced by fluvastatin. Also, strong rapid dilatation ex vivo was observed, with the equal contribution of PGI2 and NO. Our findings in cell culture experiments and in isolated human arteries indicate that fluvastatin-evoked endothelium-derived vasodilator production may confer protection of the endothelial cells via both acute and long-term effects of fluvastatin treatment. If these effects take place in vivo, we suggest a protective pleiotropic role of fluvastatin on the cardiovascular system, particularly at the level of the vascular endothelium, to ameliorate the process of atherogenesis and in the acute manner to reduce vascular tone.
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PMID:Beneficial vasoactive endothelial effects of fluvastatin: focus on prostacyclin and nitric oxide. 2121 9

A growing body of evidence suggests that oxidative stress plays a key role in the pathogenesis of micro- and macrovascular diabetic complications. The increased oxidative stress in subjects with type 2 diabetes is a consequence of several abnormalities, including hyperglycemia, insulin resistance, hyperinsulinemia, and dyslipidemia, each of which contributes to mitochondrial superoxide overproduction in endothelial cells of large and small vessels as well as the myocardium. The unifying pathophysiological mechanism that underlies diabetic complications could be explained by increased production of reactive oxygen species (ROS) via: (1) the polyol pathway flux, (2) increased formation of advanced glycation end products (AGEs), (3) increased expression of the receptor for AGEs, (4) activation of protein kinase C isoforms, and (5) overactivity of the hexosamine pathway. Furthermore, the effects of oxidative stress in individuals with type 2 diabetes are compounded by the inactivation of two critical anti-atherosclerotic enzymes: endothelial nitric oxide synthase and prostacyclin synthase. Of interest, the results of clinical trials in patients with type 2 diabetes in whom intensive management of all the components of the metabolic syndrome (hyperglycemia, hypercholesterolemia, and essential hypertension) was attempted (with agents that exert a beneficial effect on serum glucose, serum lipid concentrations, and blood pressure, respectively) showed a decrease in adverse cardiovascular end points. The purpose of this review is (1) to examine the mechanisms that link oxidative stress to micro- and macrovascular complications in subjects with type 2 diabetes and (2) to consider the therapeutic opportunities that are presented by currently used therapeutic agents which possess antioxidant properties as well as new potential antioxidant substances.
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PMID:The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro- and macrovascular complications: avenues for a mechanistic-based therapeutic approach. 2183 80

3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) are believed to exert beneficial effects against cardiovascular disease beyond correction of dyslipidemia. The aim of this combined in vitro and in vivo study was to investigate the influence of the commonly used simvastatin on prostacyclin and thromboxane A2, 2 prostaglandins with different cardiovascular effects, normally in homeostatic balance in the circulatory system. Single-dose administration of simvastatin significantly decreased urinary prostacyclin excretion of healthy volunteers (P < 0.01) and increased the ratio between thromboxane A2 and prostacyclin (2-fold increase, P < 0.01), as assessed by enzyme immunoassays of the corresponding metabolites in urine. Human vascular endothelial cells, exposed to corresponding concentrations of simvastatin and assayed in the same way, reduced the release of prostacyclin about 40% (P < 0.05), altered the transcriptional expression of cyclooxygenase and prostacyclin synthase as analyzed by real-time polymerase chain reaction, and reduced the prostacyclin synthase promoter activity by 50% (P < 0.05), evaluated in a luciferase reporter system. We speculate that simvastatin shifts the balance between thromboxane A2 and prostacyclin in favor of the thromboxane pathway in vivo, and after exposure to clinically relevant concentrations in vitro. This may have pathophysiological implications by promoting a prothrombotic state in the blood vessels.
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PMID:Influence of simvastatin on the thromboxane and prostacyclin pathways, in vitro and in vivo. 2298 53