Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Gemfibrozil (Lopid) is extensively used as lipid-regulating agent in the Western World, and its beneficial effect is demonstrated in human studies such as the Helsinki Heart Study. However, the mechanism of its hypolipidaemic action is not fully understood. In the present paper, to elucidate the hypolipidaemic mechanism, we examined the effects of gemfibrozil on lipid metabolism in the normocholesterolaemic and hypercholesterolaemic stroke-prone spontaneously hypersensitive rat (SHRSP). 2. Gemfibrozil effectively increased high density lipoprotein (HDL) subfraction rich in apoE (apoE-HDL) and significantly decreased very low density lipoprotein (VLDL) in normocholesterolaemic SHRSP. In the liver of normocholesterolaemic SHRSP, gemfibrozil significantly reduced the activity of microsomal acyl-CoA:cholesterol acyltransferase. 3. Gemfibrozil markedly reduced atherogenic beta-very low density lipoprotein (beta-VLDL) and low density lipoprotein (LDL) in hypercholesterolaemic SHRSP fed a high-fat and high-cholesterol diet (HFC diet). On the other hand, it significantly increased the contents of apoA-I, A-IV and E in the HDL fraction compared with the control group, suggesting that gemfibrozil effectively increases anti-atherogenic HDL subfractions rich in apoA-I, A-IV or E. In the liver of hypercholesterolaemic SHRSP, gemfibrozil markedly prevented lipid accumulation.
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PMID:Lipid-regulating action of gemfibrozil in the stroke-prone spontaneously hypertensive rat. 907 7

Although statins reduce the risk of non-haemorrhagic strokes and transient ischaemic attacks (TIA), little is known about the efficacy of fibrates. This situation has been partly remedied by the recent publication of two-fibrate based trials--The Veterans Affairs High Density Lipoprotein Cholesterol Intervention Trial (VAHIT) and the Bezafibrate Infarction Prevention Trial (BIP). In BIP, bezafibrate did not significantly reduce the risk of a cerebrovascular event (CVE). Bezafibrate increased the high density lipoprotein cholesterol (HDL) level by 18% to 40 mg/dl (1.03 mmol/l) and decreased triglyceride (TG) levels by 21% to 115 mg/dl (1.29 mmol/l). In contrast, in VAHIT, gemfibrozil significantly reduced the risk of investigators designated stroke (P=0.04) and TIA (P<0.001). Gemfibrozil increased HDL by 6% to 33 mg/dl (0.85 mmol/l) and decreased TG by 31% to 110 mg/dl (1.25 mmol/l). However, the baseline low density lipoprotein cholesterol (LDL) levels were higher in BIP than in VAHIT (148 versus 111 mg/dl; 3.82 versus 2.87 mmol/l). LDL levels were not markedly altered by treatment in either trial. Fibrates can improve several CVE predictors, like fibrinogen, lipoprotein (a), insulin sensitivity and platelet activity. Furthermore, lowered HDL and/or raised TG levels are associated with an increased risk of a CVE; fibrates are an appropriate treatment for this lipid profile. In conclusion, the evidence suggests that not only total cholesterol and LDL, but also HDL and TG levels predict the risk of a CVE. Statins, fibrates or a combination of these drugs can modify these variables.
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PMID:Are high density lipoprotein (HDL) and triglyceride levels relevant in stroke prevention? 1168 67

Older men and women with coronary artery disease, prior stroke, peripheral arterial disease, and extracranial carotid arterial disease with a serum low-density lipoprotein (LDL) cholesterol > 125 mg/dL despite diet should be treated with lipid-lowering drug therapy, preferably with statins, to reduce the serum LDL cholesterol to < 100 mg/dL. If statin drug therapy does not lower the serum LDL cholesterol to < 100 mg/dL in older persons with coronary artery disease, a bile acid binding resin, such as cholestyramine, should be added, since this drug does not increase the incidence of myositis in persons taking statins. The physician should use statins to treat older persons without atherosclerotic cardiovascular disease with a serum LDL cholesterol > or = 160 mg/dL plus one major risk factor, or a serum LDL cholesterol greater than or equal to 130 mg/dL plus a serum high-density lipoprotein (HDL) cholesterol < 50 mg/dL. Gemfibrozil may be useful in reducing the incidence of coronary events in persons with coronary artery disease whose primary lipid abnormality is a low serum HDL cholesterol level. There are no good data supporting treatment of hypertriglyceridemia unassociated with increased LDL cholesterol or decreased HDL cholesterol for prevention of cardiovascular disease.
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PMID:Pharmacologic therapy of lipid disorders in the elderly. 1209 73

The significant cardiovascular disease (CVD) event reduction in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) could not be fully explained by the 6% increase in high-density lipoprotein (HDL) cholesterol with the fibrate gemfibrozil. We examined whether measurement of HDL subpopulations provided additional information relative to CVD risk reduction. The HDL subpopulations were characterized by 2-dimensional gel electrophoresis in subjects who were treated with gemfibrozil (n = 754) or placebo (n = 741). In this study, samples obtained at the 3-month visit were used; and data were analyzed prospectively using CVD events (coronary heart disease death, myocardial infarction, or stroke) during the 5.1 years of follow-up. Analyses in the gemfibrozil arm showed that subjects with recurrent CVD events had significantly higher prebeta-1 and had significantly lower alpha-1 and alpha-2 HDL levels than those without such events. Prebeta-1 level was a significant positive predictor; alpha-1 and alpha-2 levels were significant negative risk factors for future CVD events. alpha-2 level was superior to HDL cholesterol level in CVD-risk assessment after adjustment for established risk factors. Gemfibrozil treatment was associated with 3% to 6% decreases in the small, lipid-poor prebeta-1 HDL and in the large, lipid-rich alpha-1 and alpha-2 HDL and with increases in the small alpha-3 (3%) and prealpha-3 (16%) HDLs. Although the use of gemfibrozil has been associated with reduction in CVD events in VA-HIT, HDL subpopulation analysis indicates that gemfibrozil-mediated improvement in CVD risk might not be the result of its effects on HDL. It is quite possible that much of the cardiovascular benefits of gemfibrozil are due to a much wider spectrum of effects on metabolic processes that is not reflected by changes in blood lipids and HDL subpopulations.
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PMID:Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial. 1807 62

Fibrates are lipid lowering drugs and found as ligands for peroxisome proliferator-activated receptors (PPARs). A clinical study has shown that one type of fibrate gemfibrozil reduces stroke incidence in men. However, it remains unknown whether gemfibrozil improves outcome after stroke. We hypothesized that prophylactic administration of gemfibrozil improves outcome after ischemic stroke. In this study, we measured the impact of gemfibrozil in two permanent middle cerebral artery occlusion (MCAO) models in young adult male mice on normal diet. First, we tested gemfibrozil in a filamentous MCAO model. Pretreatment with gemfibrozil (30 mg/kg) for 7 days moderately but significantly reduced infarct size at 24 h after MCAO. A higher dose (120 mg/kg) did not attenuate infarct size. Rather, it tended to increase brain swelling. Second, we tested in a distal MCAO model. Gemfibrozil (30 mg/kg) for 7 days before and after stroke significantly attenuated cortical lesion size at 7 days after MCAO. Cortical blood flow measured by laser speckle imaging was improved by gemfibrozil in the ischemic hemisphere. In non-stroke animals gemfibrozil also altered gene expression levels of PPARs in both the aorta and brain in organ specific manners; however, endothelial nitric oxide synthase (eNOS) was not significantly affected. These findings suggested the possibility that the observed infarct reductions and cortical blood flow improvements in ischemic brains were not through eNOS-mediated mechanisms. Further investigations may be meritorious to examine whether prophylactic usage of gemfibrozil against stroke is beneficial.
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PMID:Effects of gemfibrozil on outcome after permanent middle cerebral artery occlusion in mice. 1942 43