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)

In the present paper, we employed the stroke-prone spontaneously hypertensive rat (SHRSP) as an animal model and the Kyo: Wistar rat (WKY) as a control, and studied on the effect of repeated phase shifts in light-dark cycles on lipid metabolism. First, we investigated diurnal rhythms of the lipid metabolism in SHRSP and WKY. In both strains, the activities of lipoprotein lipase (LPL) and hepatic microsomal cholesterol 7 alpha-hydroxylase in the dark period were significantly higher than those in the light period. In addition, in SHRSP, the serum apoA-IV level in the dark period was also higher than that in the light period. Next, we repeated the phase shifts in light-dark cycles twice a week with elongation of the light period for 4 weeks. LPL activity in the light period increased in response to the repeated phase shifts in both strains. This might be a defensive reaction to maintain homeostasis in the lipid metabolism in addition to energy production. Moreover, we performed repeated phase shifts in rats fed a high-fat and high-cholesterol diet containing 0.1% propylthiouracil to elucidate the effect on the development of hypercholesterolemia. The repeated phase shifts increased the levels of atherogenic lipoproteins and the atherogenic index (apoB/apoA-I). In particular, the effect was more marked in SHRSP. This deleterious effect could be due to the overproduction of very low density lipoprotein (VLDL, beta-VLDL) in the liver.
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PMID:[Effects of repeated phase shifts in light-dark cycles on lipid metabolism in stroke-prone spontaneously hypertensive rats (SHRSP)]. 151 56

The relation between obesity and noninsulin-dependent diabetes mellitus is established. The weak association between obesity and cardiovascular disease or stroke might be attributable to a risk present only in a subgroup of obesity patients. Recent prospective studies have shown such a group to be characterized by abdominal localization of adipose tissue, reviving old empiric observations of such links. The sex-linked adipose tissue distribution is probably dependent on a balance between glucocorticoids and sex steroid hormones. The former are active mainly on intraabdominal adipose tissues through the high density of a specific receptor expressing lipoprotein lipase activity. This effect is counteracted by female sex steroid hormones, mainly progesterone, which promote fat deposition in the gluteal-femoral regions, utilized mainly during pregnancy and lactation. Testosterone stimulates lipid mobilization through transcriptional expression of beta-adrenergic receptors via a specific androgen receptor and also inhibits lipoprotein lipase activity. Intraabdominal adipose tissues, drained by the portal vein, have a very sensitive lipolytic system in men, based on an increased beta-adrenoceptor activity. This is probably a testosterone effect via the mechanisms mentioned. With testosterone deficiency, these mechanisms are less active, permitting accumulation of fat that can be reversed by testosterone substitution. Abdominal distribution of fat in men thus is probably a sign of relative testosterone deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Classification of obese patients and complications related to the distribution of surplus fat. 213 24

Recent studies have shown the predictive power of abdominal distribution of adipose tissue for the development of cardiovascular disease, stroke, diabetes as well as strong associations to the previously known risk factors for these endpoints. The reason for the accumulation of abdominal fat might be due to an imbalance between cortisol and sex steroid hormones. Cortisol receptor density seems to be particularly high in abdominal adipose tissue, leading to expression of lipoprotein lipase activity primarily here. Progesterone and testosterone seems to counteract this, the former perhaps through competition with the cortisol receptor. Accumulation of intraabdominal fat, particularly in the tissues drained by the portal circulation, probably leads to high free fatty acid concentrations in the portal vein, because of the high lipolytic sensitivity of these tissues. This in turn seems to inhibit hepatic clearance of portal insulin, leading to peripheral hyperinsulinemia, insulin resistance, perhaps hypertension as well as hyperlipidemia via drive by free fatty acids of lipoprotein synthesis in the liver. These are risk factors for diabetes, cardiovascular disease and stroke. It is of interest that subjects with abdominal adipose tissue have several factors leading to increased cortisol and low sex steroid hormone secretion, including stress, high alcohol consumption and smoking. This might provide some of the background to this syndrome.
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PMID:Obesity and adipose tissue distribution as risk factors for the development of disease. A review. 214 Jan 8

Changes in aortic lipolytic enzyme activities (cholesterol esterase and lipoprotein lipase) and acid phosphatase activity during aging were investigated in three strains of rats with different blood pressures; stroke prone spontaneously hypertensive rats (SHRSP), spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKR). The blood pressures of male, 7 month old animals, was 234 (SHRSP), 173 (SHR) and 128 (WKR) mmHg. The cholesterol esterase activity markedly decreased with age in the aortas of SHRSP, SHR and normotensive WKR rats, while acid phosphatase activity decreased only slightly, if at all, and lipoprotein lipase activity remained unchanged. This effect was enhanced by increasing blood pressure in SHRSP, SHR and WKR. The total aortic cholesterol content increased significantly with hypertension in a inverse relation with cholesterol esterase activity. These results suggest that cholesterol deposition in aged arteries is, at least partialy, ascribable to an age-related decrease in cholesterol esterase, and that hypertension aggravates the deposition of arterial cholesterol by accelerating the age-related decrease in aortic cholesterol esterase activity.
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PMID:Age and blood pressure related changes in cholesterol esterase activity and cholesterol content in aortas of stroke prone spontaneously hypertensive rats, spontaneously hypertensive rats and normotensive Wistar Kyoto rats. 742 53

Ischaemic stroke is pathogenetically heterogeneous, but there is strong evidence that genetic as well as environment factors contribute to the risk of the individual. Here we report the similar distribution of polymorphic markers of the lipoprotein lipase (LPL) gene in 128 patients with ischaemic stroke, 56 patients with carotid artery stenosis and 95 healthy control subjects, in spite of a significant influence of the Asn291-->Ser mutation on serum levels of triglycerides. We conclude that these LPL polymorphisms do not contribute greatly to the overall risk of ischaemic stroke in the general population.
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PMID:Lipoprotein lipase gene polymorphisms in ischaemic stroke and carotid stenosis. 935 44

Essential hypertension is, at least in many subjects, associated with a decrease in insulin sensitivity, whereas glycemic control is (still) normal. Metaanalyses of hypertension intervention studies revealed different efficacy of treatment on cerebral (cerebrovascular accidents [CVA]) and cardiac (coronary heart disease [CHD]) morbidity and mortality. Although CVA were reduced to an extent similar to that anticipated, the decrease in CHD was less than expected. These differences are likely to be caused by the different impact of concomitant cardiovascular risk factors, such as dyslipidemia, impaired glucose tolerance, and non-insulin-dependent diabetes mellitus on CHD and CVA. Frequently these cardiovascular risk factors are ineffectively controlled in hypertensive patients, and moreover, some of the widely used antihypertensive agents have unfavorable side effects and further deteriorate these particular metabolic risk factors. Therefore, the metabolic side effects of antihypertensive treatment have received more attention. During the past few years, studies demonstrated that most antihypertensive agents modify insulin sensitivity in parallel with alterations in the atherogenic lipid profile. Alpha1-blockers and angiotensin converting enzyme inhibitors were shown to either have no impact on or even improve insulin resistance and the profile of atherogenic lipids, whereas most of the calcium channel blockers were found to be metabolically inert. The diuretics and beta-adrenoreceptor antagonists further decrease insulin sensitivity and worsen dyslipidemia. The mechanisms by which beta-adrenoreceptor antagonist treatment exert its disadvantageous effects are not fully understood, but several possibilities exist: significant body weight gain, reduction in enzyme activities (muscle lipoprotein lipase and lecithin cholesterol acyltransferase), alterations in insulin clearance and insulin secretion, and, probably most important, reduced peripheral blood flow due to increase in total peripheral vascular resistance. Recent metabolic studies found beneficial effects of the newer vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. In many hypertensive patients, elevated sympathetic nerve activity and insulin resistance are a deleterious combination. Although conventional beta-blocker treatment was able to take care of the former, the latter got worse; the newer vasodilating beta-blocker generation seems to be capable of successfully treating both of them.
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PMID:Antihypertensive therapy and insulin sensitivity: do we have to redefine the role of beta-blocking agents? 979 45

Detraining can be defined as the partial or complete loss of training-induced adaptations, in response to an insufficient training stimulus. Detraining is characterized, among other changes, by marked alterations in the cardiorespiratory system and the metabolic patterns during exercise. In highly trained athletes, insufficient training induces a rapid decline in VO2max, but it remains above control values. Exercise heart rate increases insufficiently to counterbalance the decreased stroke volume resulting from a rapid blood volume loss, and maximal cardiac output is thus reduced. Cardiac dimensions are also reduced, as well as ventilatory efficiency. Consequently, endurance performance is also markedly impaired. These changes are more moderate in recently trained subjects in the short-term, but recently acquired VO2max gains are completely lost after training stoppage periods longer than 4 wk. From a metabolic viewpoint, even short-term inactivity implies an increased reliance on carbohydrate metabolism during exercise, as shown by a higher exercise respiratory exchange ratio. This may result from a reduced insulin sensitivity and GLUT-4 transporter protein content, coupled with a lowered muscle lipoprotein lipase activity. These metabolic changes may take place within 10 d of training cessation. Resting muscle glycogen concentration returns to baseline within a few weeks without training, and trained athletes' lactate threshold is also lowered, but still remains above untrained values.
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PMID:Cardiorespiratory and metabolic characteristics of detraining in humans. 1125 68

Variation in lipid levels has been associated with atherosclerotic vascular disease, including stroke. Genes contributing to interindividual variation in lipid levels may play a role in the etiology of stroke, either through their effects on lipid synthesis and metabolism or through separate pathways. For this reason, we sought to examine the association between polymorphisms in the lipoprotein lipase (LPL) and apolipoprotein E (APOE) genes and subclinical and clinical stroke in the Atherosclerosis Risk in Communities (ARIC) Study. Subclinical stroke was determined by cerebral magnetic resonance imaging (MRI). Subclinical cerebral infarct cases (n = 197) were compared to a stratified random sample identified from individuals participating in the MRI examination (n = 200). Incidence of clinical ischemic stroke was determined by following the ARIC cohort for an average of 7.5 years for potential cerebrovascular events; 218 validated clinical ischemic strokes were identified. A stratified random sample of the ARIC cohort (CRS, n = 964) was used as the comparison group for clinical cases. The LPL S291-carrying genotypes and APOE epsilon2- and epsilon4-carrying genotypes were not significantly associated with subclinical or clinical stroke. The LPL X447-containing genotypes were significantly associated with subclinical (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.23-15.15; P = 0.020) and clinical stroke (hazard rate ratio [HRR], 2.57; 95% CI, 1.24-5.34; P = 0.01) in men, both by themselves and after adjustment for multiple stroke risk factors. The LPL S447X polymorphism is significantly associated with subclinical cerebral infarction and incident clinical ischemic stroke in men from a middle-aged American population. This association does not appear to be mediated by triglyceride, high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels, or additional stroke risk factors.
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PMID:LPL polymorphism predicts stroke risk in men. 1192 Oct 83

Lipoprotein (LP) metabolism plays a pivotal role in atherogenesis. Breakdown of triglyceride (TG) rich lipoproteins, both of exogenous--chylomicrones and endogenous--very low density lipoproteiny (VLDL) produces remnant lipoproteins after repeated action of lipoprotein lipase (LPL). Atherogenity of remnant lipoprotein has been proved. Also atheroprotective high density lipoproteins (HDL) are produced from surface of TG rich lipoproteins during their lipolysis. Protective role of HDL particles in atherogenesis is manifested by reverse cholesterol transport from all extrahepatic cells to the liver including cells of the arterial wall. Plasma concentration of atherogenic low density lipoproteins (LPL) is regulated by the production rate of VLDL in the liver on the one hand and their utilization by selective LDL receptors (mainly in the liver) on the other hand. Number of functioning LDL receptors is regulated genetically (gene for own LDL receptor and gene for both ligands--apoprotein B and apoprotein E) and also by environmental factors. Diet low in saturated fat and cholesterol and rich in dietary fibres increases number of LDL receptors and consequently decreases LDL cholesterol concentration. Monocytes entering arterial wall when intravasal and then subendothelial concentration of LDL is increased absorb LDL and predominantly oxidized LDL by scavenger receptors. During this repeated process they are changed to macrophages, residual macrophages and foam cells. Production of foam cells represents a starting point in atherogenesis but their high presence is typical also for advanced vulnerable atherosclerotic lesions, which are prone to rupture producing clinical complication--myocardial infarction and stroke.
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PMID:[Lipid metabolism in atherogenesis]. 1269 88

Cholesteryl ester transfer protein (CETP) and lipoprotein lipase (LPL) are both key players in plasma lipoprotein homeostasis and, as such, genetically induced alterations in their respective activities may affect susceptibility to cerebrovascular diseases. In this study, we examined the distribution of two common polymorphisms, namely CETP TaqI B and LPL Ser447Ter in a cohort of Greek clinically diagnosed late-onset ischaemic stroke patients (n = 98) and an ethnicity-, age- and sex-matched control group with no manifestations of vascular disease (n = 100). Our study revealed no statistically significant differences with respect to the distribution of either polymorphism, examined separately or in combination, between the two groups.
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PMID:Cholesteryl ester transfer protein TaqI B and lipoprotein lipase Ser447Ter gene polymorphisms are not associated with ischaemic stroke in Greek patients. 1589 5


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