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)

There is evidence that indicates the involvement of environmental and genetic factors in the pathogenesis of post-stroke dementia (PSD). In the present work, we examined different polygenic influences on the risk of PSD in a series of stroke patients. We studied 150 consecutive patients evaluated 3 months after suffering acute strokes. All patients were evaluated with a prospective standard protocol and genotyped for vascular disease-associated polymorphisms in the genes coding for apolipoprotein E (including apoE coding and apoE promoter polymorphisms), angiotensin-converting enzyme (ACE) and alpha-1-antichymotrypsin (ACT). Thirty-two cases (21.3%) resulted in dementia 3 months after the stroke. In patients with PSD, the frequency of apoE epsilon 4 (0.08), ACE-D (0.64), ACT-A (0.62) alleles and apoE gene promoter polymorphisms (-491/A, 0.88; -427/C, 0.02) was similar to that of patients without PSD (apoE epsilon 4: 0.10, p=0.79; ACE-D: 0.56, p=0.36; ACT-A: 0.51, p=0.21; -491/A: 0.86, p=1.00; -427/C: 0.08, p=0.29). Our data indicate that PSD is not associated with the genetic risk factors of vascular dementia (VD) that were studied, and that additional factors may contribute to the pathogenesis of PSD.
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PMID:Apolipoprotein E, angiotensin-converting enzyme and alpha-1-antichymotrypsin genotypes are not associated with post-stroke dementia. 1273 93

1. We have previously identified strong inhibitory effects of Kabosu (Citrus sphaerocarpa Hort.) juice precipitate (KJP) on cholesterol elevation in stroke-prone spontaneously hypertensive rats (SHRSP) fed a cholesterol diet. In the present study, to elucidate the hypocholesterolaemic mechanism, we examined the effect of dietary KJP on lipid metabolism by using SHRSP fed a cholesterol-free diet. 2. Compositions of the experimental diet containing 10% KJP powder were adjusted to those of the control diet. Seven-week-old male SHRSP were fed control or experimental diet for 2 weeks with free access to the diet and water. 3. Serum levels of cholesterol, phospholipid and triglyceride of the KJP group were significantly reduced, which was due to decreases in the very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions. 4. Serum concentrations of apolipoproteins A-I and E (apoA-I and E) of the KJP group were significantly lower than those of the control group, whereas no significant differences were observed in serum apoB and apoA-IV between the two groups. 5. In liver, there were no significant differences in the contents of lipids or relative liver weight between the two groups. The activity of microsomal cholesterol 7alpha-hydroxylase of the KJP group tended to increase, whereas that of microsomal acyl-coenzyme A : cholesterol acyltransferase was significantly reduced, compared with the control group. 6. These results indicate that dietary KJP produces reductions of serum lipid levels, which are due to reductions in VLDL, apoE HDL and apoA-I HDL, and may promote catabolism and excretion of hepatic cholesterol in SHRSP fed a cholesterol-free diet.
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PMID:Hypocholesterolaemic effects of an ethanol precipitate of Kabosu juice in stroke-prone spontaneously hypertensive rats fed a cholesterol-free diet. 1289 Jan 73

Atherosclerosis is a primary cause of heart disease and stroke; it is the underlying cause of about 50% of all deaths in Western countries. It is known that early detection of atherosclerotic lesions would significantly reduce the risk of mortality. The objective of this study was to develop a radioimaging method for early detection of atherosclerotic plaques. A novel polyiodinated cholesterol analog, cholesteryl 1,3-diiopanoate glyceryl ether (C2I, patent pending), was synthesized and radiolabeled with 125I. 125I-C2I was incorporated into acetylated low-density lipoprotein (AcLDL), which is considered to be an atherosclerotic plaque-seeking carrier. 125I-C2I was also prepared as a chylomicron-like emulsion. Transgenic mice deficient in apoE and low-density lipoprotein receptors (LDLR), known as apoE/LDLR double knockout, were used as an animal model of early atherosclerosis. 125I-C2I/AcLDL or 125I-C2I emulsion was injected into the apoE/LDLR knockout mice via the tail vein, and the mice were killed humanely 24 h after injection. Various tissues including aorta were removed and radioactivity was determined. The aorta samples were also imaged to determine the accumulation of radioactivity from C2I. The images were compared to the atherosclerotic lesions revealed by histological studies. It was found that both 125I-C2I/AcLDL and 125I-C2I emulsion resulted in accumulation of radioactivity at the site of early atherosclerotic lesions, and they therefore may be useful for early detection of atherosclerosis.
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PMID:Ex vivo evaluation of a novel polyiodinated compound for early detection of atherosclerosis. 1297 7

The clinical phenotype in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), an autosomal dominant cerebral arteriopathy, is variable, but the reasons for this remain uncertain. Possible factors include the mutation site and the influence of additional modulating factors, which could include both epistatic interactions and interactions with cardiovascular risk factors known to cause sporadic small vessel disease. In a large prospectively recruited cohort of CADASIL subjects we determined relationships between phenotype and mutation site, the apoE genotype and cardiovascular risk factors. In addition to clinical features, disease severity was assessed by MRI lesion volume, measured both semiquantitatively (Scheltens scale) and quantitatively. One hundred and twenty-seven CADASIL cases from 65 families with 17 different mutations were studied. Site of mutation was not associated with the presence or age of onset of stroke, migraine, dementia, dependency or MRI lesion load. There was no evidence of intrafamilial clustering of particular phenotypes. Amongst subjects with stroke/transient ischaemic attack, smoking at the time of the event was independently associated with earlier age of onset (P = 0.01). There were no associations between age of onset or presence of stroke and other cardiovascular risk factors, including homocysteine. Homocysteine levels were higher in migraineurs [mean (SD) 12.8 (5.6) versus 9.8 (3.4) micromol/l, P = 0.02)] and elevated homocysteine was independently associated with an earlier age of onset of migraine (P = 0.01). No relationship was found between MRI lesion volume and risk factors, or between apoE genotype and phenotype. Our results show no notch 3 genotype-phenotype correlations. This implies that modulating factors influence phenotype. Smoking appears to increase the risk of stroke, while high homocysteine levels are associated with an increased risk of migraine.
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PMID:The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. 1522 30

Coxibs, such as rofecoxib, celecoxib, and valdecoxib, selectively inhibit cyclooxygenase (COX)-2, the mainly inducible, pro-inflammatory COX isoform. Unlike traditional non-steroidal anti-inflammatory drugs (NSAIDs) most coxibs do not significantly inhibit COX-1 and are therefore less toxic to the gastrointestinal tract. Hence, coxibs widely replaced traditional NSAIDs for treatment of arthritis and other painful inflammatory conditions. In many, but not all, clinical studies, coxibs became associated with higher risks of myocardial infarction (MI) and stroke. Several mechanisms may be involved in the pathogenesis of such complications. First, selective inhibition of COX-1 lowers platelet synthesis of thromboxane (TXA(2)), a thrombogenic and atherogenic eicosanoid. Selective inhibition of COX-2 limits endothelial cell synthesis of prostacyclin (PGI(2)), an arachidonic acid product that opposes the effects of thromboxane. In apoE-/- mice, interruption of TXA(2) signaling by deletion of its receptor (TP) limits atherogenesis, whereas interruption of PGI2 signaling by deletion of its receptor (IP) accelerates atherogenesis. This suggests that selective inhibition of COX-2 can disrupt the physiological balance between thromboxane and prostacyclin and thus increase atherosclerosis, thrombogenesis, and the risk of cardiovascular complications. Second, COX inhibition can raise levels of arachidonic acid, which can inhibit mitochondrial oxidative phosphorylation (OXPHOS) and increase OXPHOS generation of reactive oxygen species. Several NSAIDs, including coxibs and meloxicam, directly uncouple or inhibit OXPHOS. Studies of apoE-/- mice indicate that mitochondrial dysfunction plays an early role in atherogenesis. Third, many NSAIDs exhibit COX-independent properties. For example, in animal models, short-term treatment with celecoxib reduces monocyte chemotaxis by reducing expression of monocyte chemoattractant protein (MCP)-1. However, long-term treatment results in the opposite effect and accelerates atherogenesis. In conclusion, to reduce the risk of cardiovascular complications during long-term coxib therapy, low-dose aspirin supplementation should be considered. An alternative is to use a less COX-2-selective inhibitor such as meloxicam. Genotyping of -765 alleles of the COX-2 gene promoter and examining the polymorphism of other genes involved in eicosanoid metabolism or NSAID degradation may become helpful in predicting patients who are at higher risk of cardiovascular complications during selective COX-2 inhibitor therapy.
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PMID:Cardiovascular complications of non-steroidal anti-inflammatory drugs. 1625 52

Recently, we found that 4-hydroxyderricin, one of the major chalcones in Angelica keiskei extract (an ethyl acetate extract from the yellow liquid of stems), suppressed increases in systolic blood pressure and reduced both serum very low-density lipoprotein levels and liver triglyceride content in stroke-prone spontaneously hypertensive rats (SHRSP). In the present study, we have isolated laserpitin, a characteristic coumarin, from the A. keiskei extract and examined the effect of dietary laserpitin on blood pressure and lipid metabolism in SHRSP. Six-week-old male SHRSP were fed diets containing 0.1% laserpitin for 7 weeks with free access to the diet and water. Bodyweight gain was reduced by dietary laserpitin after 4 weeks through to 7 weeks without any significant change in daily food intake. Serum total cholesterol, phospholipid and apolipoprotein (apo) E levels were significantly increased, which was due to significant increases in cholesterol, phospholipid and apoE contents in the low- and high-density lipoprotein (LDL and HDL, respectively) fractions. These results suggest that dietary laserpitin increases serum apoE-HDL levels. In the liver, significant decreases in relative liver weight and triglyceride content were found after treatment with laserpitin for 7 weeks. An investigation of hepatic mRNA expression of proteins involved in lipid metabolism indicated that a significant decrease in hepatic triglyceride lipase may be responsible for the increase in serum HDL levels and also indicated that a marked decrease in adipocyte determination and differentiation factor 1 may be responsible, at least in part, for the decrease in hepatic triglyceride content. In conclusion, dietary laserpitin produces increases in serum HDL levels, especially apoE-HDL, and decreases in the hepatic triglyceride content in SHRSP.
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PMID:Beneficial effect of laserpitin, a coumarin compound from Angelica keiskei, on lipid metabolism in stroke-prone spontaneously hypertensive rats. 1644 77

Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.
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PMID:APOE epsilon3 gene transfer attenuates brain damage after experimental stroke. 1680 48

Dyslipidemia is a potent cardiovascular (CV) risk factor in the general population. Elevated low-density lipoprotein cholesterol (LDL-C) and/or low high-density lipoprotein (HDL-C) are well-established CV risk factors, but more precise determinants of risk include increased apoprotein B (ApoB), lipoprotein(a) [Lp(a)], intermediate and very low-density lipoprotein (IDL-C, VLDL-C; "remnant particles"), and small dense LDL particles. Lipoprotein metabolism is altered in association with declining glomerular filtration rate such that patients with non dialysis-dependent chronic kidney disease (CKD) have lower levels of HDL-C, higher triglyceride, ApoB, remnant IDL-C, remnant VLDL-C, and Lp(a), and a greater proportion of oxidized LDL-C. Similar abnormalities are prevalent in hemodialysis (HD) patients, who often manifest proatherogenic changes in LDL-C in the absence of increased levels. Patients treated with peritoneal dialysis (PD) have a similar but more severe dyslipidemia compared to HD patients due to stimulation of hepatic lipoprotein synthesis by glucose absorption from dialysate, increased insulin levels, and selective protein loss in the dialysate analogous to the nephrotic syndrome. In the dialysis-dependent CKD population, total cholesterol is directly associated with increased mortality after controlling for the presence of malnutrition-inflammation. Treatment with statins reduces CV mortality in the general population by approximately one third, irrespective of baseline LDL-C or prior CV events. Statins have similar, if not greater, efficacy in altering the lipid profile in patients with dialysis-dependent CKD (HD and PD) compared to those with normal renal function, and are well tolerated in CKD patients at moderate doses (<or=20 mg/day atorvastatin or simvastatin). Statins reduce C-reactive protein as well as lipid moieties such as ApoB, remnants IDL and VLDL-C, and oxidized and small dense LDL-C fraction. Large observational studies demonstrate that statin treatment is independently associated with a 30%-50% mortality reduction in patients with dialysis-dependent CKD (similar between HD- and PD-treated patients). One recent randomized controlled trial evaluated the ability of statin treatment to reduce mortality in type II diabetics treated with HD ("4D"); the primary end point of death from cardiac cause, myocardial infarction, and stroke was not significantly reduced. However, results of this trial may not apply to other end-stage renal disease populations. Two ongoing randomized controlled trials (SHARP and AURORA) are underway evaluating the effect of statins on CV events and death in patients with CKD (including patients treated with HD and PD). Recruitment to future trials should be given a high priority by nephrologists and, until more data are available, consideration should be given to following published guidelines for the treatment of dyslipidemia in CKD. Additional consideration could be given to treating all dialysis patients felt to be at risk of CV disease (irrespective of cholesterol level), given the safety and potential efficacy of statins. This is especially relevant in patients treated with PD, given their more atherogenic lipid profile and the lack of randomized controlled trials in this population.
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PMID:Statins for treatment of dyslipidemia in chronic kidney disease. 1729 64

Peripheral arterial disease (PAD) is associated with coronary artery disease (CAD) and stroke, but data on the relationship between PAD and acute ischemic stroke are lacking. Therefore, we investigated this relationship. A total of 101 patients were enrolled on admission to Harasanshin General Hospital (Fukuoka, Japan) with their first ischemic stroke. All 101 patients underwent cranial CT and/or brain magnetic resonance imaging, duplex ultrasonography of the extracranial carotid arteries, and transthoracic echocardiography. The subjects were aged 41 to 92 years. PAD was present in 81/101 patients (80.2%), including 57/73 (78.1%) with small artery occlusion, 11/13 (84.6%) with large artery occlusion, and 13/15 (86.7%) with cardiogenic embolism. In 42 of these 81 patients (51.9%), PAD was asymptomatic. Serum apoprotein A1 levels were significantly higher and the intima-media thickness was significantly greater in the patients with PAD than in those without PAD. The modified Rankin scale score was significantly higher on admission in patients with PAD than in those without PAD. Stepwise logistic regression analysis revealed that the apoprotein A1 level and the modified Rankin scale score on admission were strongly associated with the occurrence of stroke in patients with PAD. Our results suggest that PAD is frequently associated with acute ischemic stroke. It may be important to perform screening for PAD in patients who have suffered an ischemic stroke.
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PMID:Impact of peripheral arterial disease and acute ischemic stroke. 1717 80

F11R is the gene name for an adhesion protein, called the F11-receptor, aka JAM-A, which under normal physiological conditions is expressed constitutively on the surface of platelets and localized within tight junctions of endothelial cells (EC). Previous studies of the interactions between human platelets and EC suggested that F11R/JAM-A plays a crucial role in inflammatory thrombosis and atherosclerosis. The study reported here obtained in-vivo confirmation of this conclusion by investigating F11R/JAM-A protein and mRNA in patients with aortic and peripheral vascular disease and in an animal model of atherosclerosis. Molecular and immunofluorescence determinations revealed very high levels of F11R/JAM-A mRNA and F11R/JAM-A protein in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with 12-week-old atherosclerosis-prone apoE-/- mice, an age in which atherosclerotic plaques are well established. Enhanced expression of the F11R/JAM-A message in cultured EC from human aortic and venous vessels was observed following exposure of the cells to cytokines. Determinations of platelet adhesion to cultured EC inflamed by combined cytokine treatment in the presence of F11R/JAM-A - antagonists provided data indicating that de novo expression of F11R/JAM-A on the luminal surface of inflamed EC has an important role in the conversion of EC to a thrombogenic surface. Further studies of these interactions under flow conditions and under in-vivo settings could provide a final proof of a causal role for F11R/JAM-A in the initiation of thrombosis. Based on our in-vitro and in-vivo studies to date, we propose that therapeutic drugs which antagonize the function of F11R/JAM-A should be tested as novel means for the prevention and treatment of atherosclerosis, heart attacks and stroke.
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PMID:The F11 receptor (F11R/JAM-A) in atherothrombosis: overexpression of F11R in atherosclerotic plaques. 1726 57


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