Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pregnancy-induced hypertension (PIH), which includes both gestational hypertension and preeclampsia, is a common and morbid pregnancy complication for which the pathogenesis remains unclear. Emerging evidence suggests that insulin resistance, which has been linked to essential hypertension, may play a role in PIH. Conditions associated with increased insulin resistance, including gestational diabetes, polycystic ovary syndrome, and obesity, may predispose to hypertensive pregnancy. Furthermore, metabolic abnormalities linked to the insulin resistance syndrome are also observed in women with PIH to a greater degree than in normotensive pregnant women: These include glucose intolerance, hyperinsulinemia, hyperlipidemia, and high levels of plasminogen activator inhibitor-1, leptin, and tumor necrosis factor-alpha. These observations suggest the possibility that insulin resistance may be involved in the pathogenesis of PIH and that approaches that improve insulin sensitivity might have benefit in the prevention or treatment of this syndrome, although this requires further study.
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PMID:Brief review: hypertension in pregnancy : a manifestation of the insulin resistance syndrome? 1123 Feb 77

We succeeded in developing a novel rabbit model of nonsteroid and nontraumatic osteonecrosis (ON) by use of a single- and low-dose lipopolysaccharide (LPS) injection. This model is simple and highly reproducible for the frequent development of multifocal and widespread ON lesions. Male adult Japanese white rabbits intravenously injected with a single injection of 10 microg/kg body weight of LPS were histopathologically examined in the early phase (3 [n = 3], 5 [n = 3], and 24 h [n = 3]) and at 4 weeks (n = 22). Seventy-seven percent of the rabbits developed multifocal ON 4 weeks after LPS injection. ON was also observed in the femoral and humeral condyle. The average percentage of necrotic area/total area examined was 86.7 +/- 29.1% and 78.8 +/- 16.7% in the proximal one third of both the femoral and humeral bones, respectively. Organized thrombi in the intraosseous small-sized arteries and arterioles were frequently seen in and around the necrotic tissues. In the early phase, LPS treatment prominently induced thrombocytopenia, hyperlipidemia, and increased plasma levels of plasminogen activator inhibitor-1 (PAI-1). The plasma level of PAI-1 was significantly higher in the rabbits with ON than in those without ON (p < 0.01). The immunohistochemical expression of tissue factor was exaggerated in monocytes/macrophages and adipocytes in both the femoral and humeral bones of the LPS-treated rabbits. Histologically, marrow necrosis and fibrin thrombi could be observed at 24 h. In addition, pretreatment with an anticoagulant, warfarin potassium, significantly decreased the incidence of LPS-induced ON (33%, n = 9, p < 0.05) associated with elongation of prothrombin time. The results of our study show that a single administration of low-dose lipopolysaccharide induces multifocal and widespread ON characterized by the pathophysiological participation of hypercoagulability in ON development. Therefore, this model would be useful for elucidating the pathogenesis of nonsteroid ON in humans especially inflammatory hypercoagulability-induced as well as for developing preventive and therapeutic strategies.
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PMID:Osteonecrosis induced by a single administration of low-dose lipopolysaccharide in rabbits. 1142 53

Hypercoagulable states due either to inherited or acquired thrombotic risk factors are only present in approximately half of cases of DVT, but the causes in the other half, remain unknown. The importance of biological risk factors such as hyperlipidemia, hypofibrinolysis and hemorheological alterations in the pathogenesis of DVT has not been well established. In order to ascertain whether the above mentioned biological factors are associated with DVT and could constitute independent risk factors, we carried out a case-control study in 109 first DVT patients in whom inherited or acquired thrombophilic risk factors had been ruled out and 121 healthy controls age (42+/-15 years) and sex matched. From all the biological variables analyzed (cholesterol, triglycerides, glucose, fibrinogen, erythrocyte aggregation, hematocrit, plasma viscosity and PAI-1) only fibrinogen concentration reached a statistically significant difference on the comparison of means (290+/-73 mg/dl in cases vs 268+/-58 mg/dl in controls, p<0.05). After this continuous variables were dichotomized according to our reference values, the percentage of cases with cholesterolemia >220 mg/dl, hematocrit >45% and fibrinogen >300 mg/dl was higher in cases than in controls: 38% vs 22%; p<0.01; 43% vs 27%; p<0.05; 36% vs 23%; p<0.05, respectively. The percentage of cases with PAI-1 values >30 ng/ml, 37% vs 25% was borderline significant; p=0.055. Multivariate logistic regression analysis showed that cholesterolemia >220 mg/dl and fibrinogen >300 mg/dl constitute independent predictors of venous thrombotic risk. The adjusted OR's were 2.03 (95% CI; 1.12-3.70) for cholesterolemia and 1.94 (95% CI; 1.07-3.55) for fibrinogen. When these two variables combined DVT risk rose about fourfold (3.96; p<0.05). Our results suggest that hypercholesterolemia and hyperfibrinogenemia should be added to the list of known DVT risk factors and we recommend adopting measures to decrease these variables in the population with a high risk of DVT.
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PMID:Biological risk factors for deep vein trombosis. 1190 70

Monoclonal antibody therapies have conducted to not only hematologic malignancies but also disorders of hemostasis and coagulation. This article describes the recent advances of monoclonal antibody therapy for bleeding disorders such as idiopathic thrombocytopenic purpura(ITP), hemophilia A, disseminated intravascular coagulation(DIC), and thrombosis. Rituximab, chimeric anti-CD20 monoclonal antibody treatment has a valuable effect in the patients with ITP, and clinical trials using anti-CD40 ligand monoclonal antibody for ITP are underway. Anti-CD40 ligand monoclonal antibody can be an alternative therapy for hemophilia A patients with inhibitors to factor VIII. In thrombosis, anti-tissue factor monoclonal antibody and anti-factor IX(a) monoclonal antibody were established as novel anticoagulant regents. Plasminogen activator inhibitor-1(PAI-1) increases in endotoxin-induced DIC and many thrombotic diseases such as myocardial infarction, type 2 diabetes mellitus, and hyperlipidemia. Anti-PAI-1 monoclonal antibody reduced fibrin deposition in DIC mouse model. Treatment of these monoclonal antibodies for the molecules regulating coagulation-fibrinolysis system may be utilized for acute coronary syndrome and venous thrombosis.
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PMID:[Monoclonal antibody therapy for disorders of hemostasis and coagulation]. 1190 68

About 15% of the adult Kuwaiti population has type 2 diabetes and over 50% are hyperlipidaemic by current diagnostic criteria. Not surprisingly, coronary heart disease (CHD) is the leading cause of death in Kuwait. Reports from coronary care units in Kuwait suggest that 40-80% of the CHD patients were diabetic and 50-80% hyperlipidaemic. The pattern worldwide is similar. International guidelines have therefore consistently recognised diabetes as a major risk factor for CHD. In our Lipid Clinic population in Kuwait, about 30% are diabetic. The commonest lipid abnormalities seen in Kuwaiti diabetic patients, as elsewhere, are hypertriglyceridaemia with low HDL levels and variable LDL levels. About 75% of the subjects had either mixed hyperlipidaemia or predominant hypertriglyceridaemia. There are possibly some compositional changes in LDL in the diabetic subjects in that there were important differences in the statistical relationships between LDL and HDL and their respective apolipoproteins - apo B and apo A-1 in diabetic as compared to non-diabetic subjects. Other important observations made in diabetic subjects in Kuwait are: (i) similar serum Lp (a) levels and pattern of apo(a) polymorphism with non-diabetic subjects, with no demonstrable relationship between serum levels of Lp(a) and insulin/insulin sensitivity, although with CHD, Lp(a) levels were increased; (ii) diabetic hyperlipidaemic subjects had elevated PAI-1 levels with significant correlations between blood PAI-1 and insulin levels suggesting underlying insulin resistance (syndrome X). Various landmark trials of cholesterol-lowering therapies in the prevention of CHD have consistently demonstrated near-normalization of the increased CHD risk in diabetes. Our experience in Kuwait suggests that diabetic patients and others with mixed hyperlipidaemia benefit from tight glycaemic control, appropriate advice on diet and exercise with regular reinforcement by continuing contact with professional dietitians and regular availability of drugs where prescribed. Often, it is the regular compliance with medication that is important, rather than the specific medication used particularly where HMG CoA reductase inhibitors (statin drugs) are not always available. A useful guideline for management of dyslipidaemia in diabetes is suggested.
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PMID:Diabetic dyslipidaemia in Kuwait. 1244 10

Increased plasma plasminogen activator inhibitor-1 (PAI-1) has been implicated in the development of vascular disease. In type 2 diabetes mellitus high PAI-1 levels are associated with increased plasma concentrations of free fatty acids (FFA) and triacylglycerol indicating an association or a causal relationship. To answer that question, the effect of FFA/triacylglycerol on plasma PAI-1 was examined. Ten healthy male volunteers were studied for 6 h during infusion of triacylglycerol [1.5 ml/min]/heparin [0.2 IU/(kg.min)] (LIP; n=10), saline only (SAL; n=10), and saline/heparin (HEP; n=5). Plasma insulin concentrations were kept constant at approximately 35 pmol/l by intravenous somatostatin-insulin infusions and there was no significant change in plasma glucose levels during any of the study protocols. LIP increased plasma triacylglycerol and FFA approximately 3- (p < 0.001) and approximately 8- (p < 0.000001) fold, respectively, within 90 min. Baseline plasma PAI-1 measured by a bio-immunoassay was similar in HEP (11.4 +/- 2.8 ng/ml), SAL (16.6 +/- 3.6 ng/ml), and LIP studies (15.2 +/- 3.4 ng/ml). Since studies were initiated in the morning, PAI-1 decreased (p < 0.025) over time following its normal diurnal variation to 6.4 +/- 2.0 ng/ml and 4.0 +/- 2.4 ng/ml at 360 min in SAL and HEP, respectively. During LIP, however, PAI-1 increased to approximately 2.6 fold higher levels than during SAL at 360 min (16.4 +/- 4.0 ng/ml, p < 0.01). While tissue plasminogen activator (tPA) and adipsin, an adipocyte derived protease, were unaffected by LIP, changes in soluble vascular cell adhesion molecule-1 (sVCAM-1) were significantly correlated (p = 0.02) with those seen for PAI-1. This suggests that hyperlipidemia independent of insulin and plasma glucose levels stimulates vascular tissue and in turn might induce an increase in plasma PAI-1. PAI-1 then could contribute to the development of atherothrombotic vascular disease.
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PMID:Increased plasma levels of plasminogen activator inhibitor-1 and soluble vascular cell adhesion molecule after triacylglycerol infusion in man. 1295 10

The cause of many myocardial infarctions is occlusive thrombosis, or a blood clot that stops blood flow in a coronary artery. Hemostasis involves a complex system of factors, which normally form and degrade blood clots, that work within a delicate balance. Emerging evidence suggests that some hemostatic factors, including factor VII, fibrinogen, and plasminogen activator inhibitor-1, are associated with increased risk for cardiovascular disease (CVD). Accumulating evidence suggests a relationship between dietary fatty acids and emerging hemostatic CVD risk factors, although much of this evidence is incomplete or conflicting. Dietary supplementation with marine n-3 fatty acids prolongs bleeding time and may decrease risk for thrombosis. Factor VII coagulant activity modestly decreases with reductions in saturated fatty acid (SFA) intake and thereby may contribute to the beneficial effects of low SFA diets. Large triglyceride-rich particles formed during postprandial lipemia can support the assembly and function of coagulation complexes and seem to play a role in the activation of factor VII, and thus may partially explain increased CVD risk associated with increased postprandial triglyceridemia. As our understanding of the role of dietary fatty acids and hemostasis evolves, it is likely that we will be able to make specific dietary recommendations to further decrease CVD risk. At this juncture, however, increasing marine n-3 fatty acids and decreasing certain SFAs are leading strategies to reduce hemostatic CVD risk factors. An array of dietary strategies that target multiple CVD risk factors could have a greater impact on CVD than a single risk factor intervention strategy.
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PMID:Dietary fatty acids, hemostasis, and cardiovascular disease risk. 1499 64

Recent progress in adipocyte-biology shows that adipocytes are not merely fat-storing cells but that they secrete a variety of hormones, cytekines, growth factors and other bioactive substabces, conceptualized as adipocytokines. These include plasminogen activator inhibitor 1(PAI-1), tumor necrosis factor(TNF-alpha), leptin and adiponectin. Dysregulated productions of these adipocytekines participate in the pathogenesis of obesity-associated metabolic syndrome such as insulin resistance, type 2 diabetes, hyperlipidemia, and vascular diseases. Increased productions of PAI-1 and TNF-alpha from accumulated fat contribute to the formation of thrombosis and insulin resistance in obesity, respectively. Lack of leptin causes metabolic syndrome. Adiponectin exerts insulin-sensitizing and anti-atherogenic effects, hence decrease of plasma adiponectin is causative for insulin resistance and atherosclerosis in obesity.
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PMID:[Adipocytokines and metabolic syndrome--molecular mechanism and clinical implication]. 1520 45

This study assessed markers of vascular endothelial cell dysfunction associated with early atherosclerosis in carotid arteries. We measured the plasma levels of free-form tissue factor pathway inhibitor (free TFPI), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor (vWF) in 522 adults without cardiovascular disease enrolled in the Suita Study. For each sex, we analyzed the association of the degree of intimal-medial thickness (IMT) with hemostatic markers using logistic regression analysis considering potential confounding risk factors, including age, body mass index, lifestyle (current smoking and drinking), illness (diabetes mellitus and hyperlipidemia), systolic blood pressure, and antihypertensive drug use. The age-adjusted levels of free TFPI and PAI-1 were positively and independently associated with the degree of IMT for men. Even after adjustment for all confounding factors, the level of PAI-1 was positively associated with the degree of IMT. These results indicate that measurement of the levels of free TFPI and PAI-1 is a potentially useful tool for the detection of early atherosclerosis in men.
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PMID:Potential of free-form TFPI and PAI-1 to be useful markers of early atherosclerosis in a Japanese general population (the Suita Study): association with the intimal-medial thickness of carotid arteries. 1538 Apr 59

The effects of cerivastatin and fenofibrate on proteins involved in haemostasis and on markers of inflammation were investigated in otherwise healthy middle-aged males with combined hyperlipidemia. Besides classical risk factors, other so-called novel risk factors for coronary artery disease are seen to be playing an increasingly important role in the development and progression of atherosclerosis. Thirty-eight males, aged 49 +/-5 years were randomised to 12 weeks treatment either with cerivastatin at a daily dose of 0.2 mg to 0.4 mg to achieve the LDL cholesterol goal of <3.0 mM, or with fenofibrate 250 mg daily. Fasting serum lipids, homocysteine, total and free tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor (PAI-1) and tissue plasminogen activator (t-PA) antigen and activity, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured. No change in homocysteine level was observed in the cerivastatin group, while after fenofibrate administration it increased (p <0.0001). Total TFPI decreased significantly after cerivastatin (p = 0.002), but not after fenofibrate. Free TFPI did not decrease after either drug. Neither drug affected (t-PA) antigen and activity, while fenofibrate increased PAI-1 antigen (p <0.05) and activity (p <0.05). Cerivastatin decreased serum CRP values by 49.5% (p = 0.001), and fenofibrate by 29.8% (p = 0.03). The decreases of CRP in the two groups differed significantly (p = 0.04). IL-6 levels decreased significantly in the fenofibrate group (39%; p <0.0001), but not in the cerivastatin group (15%; p = 0.24) No significant decreases were observed for TNF-alpha. Cerivastatin had neutral effects on fibrinolysis, homocysteine or coagulation. On the other hand, fenofibrate increased PAI-1 antigen and activity and homocysteine, and did not affect coagulation. Both cerivastatin and fenofibrate reduced CRP levels, the decrease being significantly greater after cerivastatin. Fenofibrate also significantly decreased IL-6.
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PMID:Statin and fibrate treatment of combined hyperlipidemia: the effects on some novel risk factors. 1554 43


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