Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analysed the relationship between fasting plasma glucose, carotid intima media thickness and some atherosclerosis risk factors in 307 non-diabetic individuals. Male (n = 120) and female subjects (n = 187) with a familial history of Type II diabetes mellitus and/or obesity and hyperlipoproteinaemia were examined in the age group 40-70 years. Plasma triglycerides, total and high-density-lipoprotein cholesterol, plasminogen activator inhibitor were measured by conventional methods. Specific insulin, pro-insulin and C-peptide were measured by specific enzyme immunoassay. Intima media thickness increased in quintiles for fasting plasma glucose in men, but not in women. There was a rise of triglycerides, body mass index, waist to hip ratio, plasminogen activator inhibitor, true insulin, proinsulin, C-peptide and a decrease of high-density-lipoprotein cholesterol in quintiles for fasting plasma glucose. Fasting plasma glucose was found to be significantly positively correlated to intima media thickness, body mass index, waist to hip ratio, haemoglobin A1c, insulin, C-peptide, triglycerides, plasminogen activator inhibitor and significantly negatively correlated to high density lipoprotein cholesterol. However, the correlation of fasting plasma glucose to intima media thickness was no longer significant after adjustment for age and sex. After adjustment for age and sex intima media thickness was significantly correlated to body mass index, total cholesterol, triglycerides, albuminuria and inversely correlated to high-density-lipoprotein cholesterol. In multivariate analysis age, male sex, high-density-lipoprotein cholesterol and total cholesterol were significant determinants of intima media thickness. Our data suggest that a weak association exists between fasting plasma glucose and intima media thickness, which may be mediated by a clustering of risk factors in the upper range of non-diabetic fasting plasma glucose level with a central role for dyslipidaemia.
 ...
PMID:Relationship between fasting plasma glucose, atherosclerosis risk factors and carotid intima media thickness in non-diabetic individuals. 1033 63

Diabetes mellitus is associated with an increased incidence and greater severity of primary atherosclerosis as well as restenosis after angioplasty for reasons not yet clear. We have shown previously that insulin and proinsulin-typically elevated in blood in patients with type II diabetes-increase plasma activity of plasminogen activator inhibitor type 1 (PAI-1)in vivo. Others have demonstrated that increased PAI-1 activity is associated with coronary heart disease. Accordingly, the present study was performed to identify sites of increased expression of the PAI-1 gene within the vessel wall. Equimolar concentrations of insulin, proinsulin, or vehicle alone as a control, were administered intravenously over 1 h to conscious rabbits that were kept euglycemic throughout by the use of glucose clamping. Within 3 h plasma PAI-1 activity increased from 1.15+/-1.34 to 11.33+/-4.30 AU/ml with insulin (mean+/-s.d., P=0.015) and from 2.83+/-0.74 to 15.43+/-4.70 AU/ml with proinsulin (P=0.035). This was found to be in contrast to the controls where the increase in plasma PAI-1 activity was of lesser degree (2.43+/-1.86 to 6.80+/-1.10 AU/ml, P=n.s., n=4 each). As judged from the results of in situ hybridization, the site of prominent aortic expression of the PAI-1 gene was the endothelium. Furthermore, expression increased further in this site after administration of insulin or proinsulin. As judged from results of immunohistochemistry, PAI-1 protein in the aorta was also prominent in endothelium. These results suggest that "hyper(pro)insulinemia", increases PAI-1 not only in blood but also in arterial endothelium. Thus, attenuation of vasculopathy and especially of restenosis after angioplasty in type II diabetes may be possible with somatic gene therapy targeting PAI-1 expression in endothelial cells.
 ...
PMID:Augmentation of arterial endothelial cell expression of the plasminogen activator inhibitor type-1 (PAI-1) gene by proinsulin and insulin in vivo. 973 40

Insulin resistance (IR) is associated with an elevated PAI-1 level and by correlation with insulin and triacylglycerol (TG) levels. While in IR non-diabetics this relationship is close, in patients with NIDDM the mutual relationship is less marked and there are other factors which raise the PAI-1 levels such as proinsulin, oxidation stress or cytokines. Therefore achievement of satisfactory metabolic control, reduction of insulin and TG levels need not be associated with normalization of PAI-1. As it is an independent risk factor of atherosclerosis, further examinations are necessary in order to differentiate in more detail the possible causes of its rising level in order to obtain a rational basis for effective therapy.
 ...
PMID:[Plasminogen activator inhibitor (PAI-1) and diabetes mellitus. II. PAI-1 in insulin resistant conditions]. 982 87

To evaluate correlates between electrocardiographic QT dispersion and coronary atherosclerosis in patients with aortic stenosis before aortic valve replacement, 39 consecutive patients >40 years old with symptomatic aortic stenosis and coronary diameter narrowing > or =50% measured by digital angiographic study were included. An additional matched group with insignificant coronary lesions (<50%) consisted of 39 patients for comparisons. Matching by age, sex heart rate and incidence of chest pain resulted in two comparable groups with identical baseline characteristics. Preoperative transthoracic echocardiography and electrocardiograms were performed in all subjects. QT dispersion was defined as the difference between maximal and minimal QT interval measurements occurring among any of the 12 leads on a standard electrocardiogram. No subject had fewer than nine measurable leads. There were no significant differences of risk factors of coronary artery disease between the two groups. From a conditional multivariate logistic regression analysis, independent predictors of development of coronary artery disease in aortic stenosis were only QTc dispersion (odds ratio= 1.255, P=0.01). A wide QTc dispersion > or =70 ins) correlated with the presence of angiographically significant coronary artery disease with a sensitivity and specificity of 72% and 79%. The positive accuracy of having significant coronary artery disease in the presence of QTc dispersion > or =70 ms was 78%. The negative predictive value was 74%. In conclusion, electrocardiographic QTc dispersion may provide important clinical information. A wide QTc dispersion in patients with aortic stenosis is associated with a high incidence of coronary artery disease. These findings warrant further investigation in a large trial.
 ...
PMID:Association of increased QT dispersion with coronary atherosclerosis in patients with aortic stenosis. 987 79

Atherogenesis in the vasculature is accelerated by changes in the dynamic equilibrium between endogenous tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1). Increased expression of PAI-1, decreased expression of tissue plasminogen activator, or both can lead to decreased fibrinolytic activity and predispose to thrombosis. Increased concentrations of insulin (and proinsulin) in the plasma increase plasma PAI-1, although the mechanisms of this effect are not known. In addition, it has been observed that basal fibrinolytic activity is decreased in patients with type 2 diabetes; this may accelerate atherosclerosis by exposing vascular luminal wall surfaces to persistent and recurrent thrombi. Abnormalities in the vessel wall appear to contribute to the increased risk. There is also evidence that PAI-1 content is increased in atherosclerotic lesions of patients with type 2 diabetes, suggesting that interventions to reduce insulin resistance and improve glycemic control may improve the fibrinolytic response. Clinical studies in patients with polycystic ovary syndrome (characterized by insulin resistance, hyperinsulinemia, ovarian androgen overproduction, and impaired fibrinolytic capacity) demonstrated that treatment with troglitazone, an insulin-sensitizing agent, can markedly reduce blood levels of PAI-1. There is also clinical evidence that these agents may contribute to regression of intimal medial thickness in patients with type 2 diabetes, providing further indication that antidiabetic interventions may help inhibit the progression of early atherosclerotic lesions.
 ...
PMID:Insulin resistance and thrombosis: a cardiologist's view. 1041 58

Hyperleptinemia is considered to be one of predictors of early atherosklerosis complications. This stimulated us to investigate differences between leptinemia in persons with accelerated atherosclerosis and leptinemia in probands without atherosclerosis complications. The study also verified whether leptinemia and its relationship to other anthropometric and biochemical parameters can differ in hypolipemic-treated probands and hypolipemic-untreated individuals. We examined 89 probands with accelerated atherosclerosis. The controls were 20 persons without any signs of accelerated atherosclerosis. Probands with accelerated atherosclerosis had a slight hyperglycemia and were slightly obese, but they did not meet criteria of metabolic cardiovascular syndrome. No significant differences between both groups under study were found in terms of anthropometric and biochemical parameters (BMI, % body fat, glycemia, insulin, C-peptide, intact proinsulin, total proinsulin cholesterol, HDL, triglycerides, LDL, homeostatic model of insulin secretion and resistance). Leptin concentration was not different as well. Stratification into males and females showed that women had a significantly higher leptinemia and fat tissue mass. Other biochemical parameters were similar in both groups. We suppose that in individuals without signs of metabolic syndrome, leptinemia does not belong among predictors of accelerated atherosclerosis. The accelerated atherosclerosis persons were then divided into subgroups according to medication (28 probands--pravastatin Lipostat 20, 15 probands--phenofibrate Lipanthyl 200M, 9 probands--simvastatin Zocor 20, 47 probands--no hypolipemic medication). No significant differences between the groups were found in terms of the analysed anthropometric and biochemical parameters, except leptinemia. The pravastatin-medicated probands had a significantly lower leptinemia (significant at 99% significance level) which was evidently sex-related than other patients. The pravastatin-administered persons showed no correlation between leptinemia and body fat mass (in contrast to other groups where such a correlation was highly statistically significant). These findings can be explained by a still unclear effect of pravastatin on insulin metabolism and on other factors involved in leptin synthesis and elimination. Thus, a new therapeutic effect of pravastatin can be supposed. This may account for a highly favourable effect of pravastatin on reduced manifestations of atherosclerosis complications event at a low LDL cholesterol decrease (particularly in persons with metabolic cardiovascular syndrome).
 ...
PMID:[Serum leptin, early atherosclerosis and hypolipidemia (a new, previously undescribed effect of pravastatin, a hypolipemic agent)]. 1042 91

Hypofibrinolysis caused by increased PAI-1 levels in patients with insulin resistance (IR) is one of the most common acquired prothrombotic states with higher risk of arterial thrombosis associated with atherosclerosis. Increased PAI-1 levels are caused by PAI-1 hyperproduction in various compartments owing to various factors (multicompartmental and multifactorial model). Metabolic compartment, including visceral adipocytes and hepatocytes, is sensitive on stimulative action of insulin, proinsulin and some cytokines. This pool is responsible for elevated PAI-1 levels in obesity. Vascular compartment, including mainly endothelium, is sensitive on thrombin, angiotensin IV, cytokines, biological active lipids and oxidative stress effect, while insulin inhibits cytokine induced PAI-1 production on contrary. This compartment is responsible for elevated PAI-1 levels in patients with type 2 diabetes mellitus and hypertension with endothelial dysfunction. PAI-1 levels in patients with IR represent cumulative production in described compartments.
 ...
PMID:[A multicomparmental and multifactorial model of production of plasminogen activator inhibitor (PAI-1). I. Experimental studies]. 1042 16

The fractional catabolic rate (FCR) for low density lipoprotein (LDL) apolipoprotein B (apo B) was studied to explore the variations in apo B as a possible cause of hypercholesterolemia. The FCR of radioiodine labelled autologous LDL and homologous LDL isolated from a normocholesterolemic subject were compared in forty-nine type II hypercholesterolemic males and females with the mean plasma concentration of total cholesterol of 7.78 mmol/l, LDL-cholesterol 5.41 mmol/l and triglycerides 2.09 mmol/l. In most patients the autologous LDL was catabolized at an equal rate and sometimes even faster than the homologous LDL. However, twelve out of forty-nine patients catabolized homologous LDL 0.8-19.3% faster than autologous LDL and several apo B polymorphisms were determined. No apo B-3500 or apo B-3531 mutations were detected. Patients with XbaI -/- (absence of cutting site) had lower total, IDL and LDL cholesterol and LDL apoB than the other genotypes. Patients with EcoRI +/+ (presence of cutting site) had higher total, VLDL and LDL cholesterol and slower FCR for autologous LDL, and their VLDL was richer in cholesterol than that of patients with the EcoRI +/-. The MspI and ins/del polymorphisms were not associated with variations in the measured parameters. The apo E 4 was associated with higher VLDL and IDL cholesterol, higher triglycerides and LDL apo B than E 3/3. Overall, the determined apo B polymorphisms were not related to the slow clearance of autologous LDL among the 12 patients, in whom autologous LDL was cleared at a slower rate than homologous LDL. In conclusion, hypercholesterolemia can be due to particle-related slow clearance of LDL in some patients. However, this is not a common cause of hypercholesterolemia.
Atherosclerosis 1999 Sep
PMID:Variation of apolipoprotein B as a possible cause of decreased low density lipoprotein clearance and hypercholesterolemia. 1048 80

Leptin receptors are supposed to have signal effects and are located in most tissues in the organism but we failed to find literary data on concentration (measurement) of leptin receptors in the system circulation. We examined by the method of randomized selection the group of 20 patients with manifested atherosclerosis in whom BMI was calculated. Then we analyzed concentration of leptin receptor (double sandwich ELISA, standard recombinant human leptin), leptin, glucose, insulin, proinsulin, CRP and uric acid in the serum. The control group consisted of 103 probands without signs of atherosclerosis or other manifested diseases. The control group was subjected to determination of BMI, leptin and leptin receptor in the serum. Concentration of leptin receptor does not differ significantly between the patients with atherosclerosis and normal population. Probands with atherosclerosis showed a very close negative correlation between concentration of leptin receptor and leptinemia which is absent in normal population.
 ...
PMID:Determination of leptin receptor in the serum and relations to laboratory and anthropological parameters in patients with atherosclerotic complications. 1074 33

So far little is known about the importance of different types of non-diabetic hyperglycemia for the development of macrovascular disease. The aim of this work was to examine the intima-media thickness (IMT) of the common carotid artery (CCA), a well-accepted marker of atherosclerosis, as well as various risk factors for atherosclerosis in non-diabetic subjects with isolated fasting (IFH; n=67), isolated postchallenge (IPH; n=82) and combined hyperglycemia (CH; n=88) in comparison to normoglycemic (NG; n=265) controls. Subjects were participants of the RIAD study (Risk Factors in IGT for Atherosclerosis and Diabetes). IMT in the IPH (IMTmean: 0.89+/-0.02 mm; IMTmax: 1.01+/-0.02 mm; mean+/-SEM) and CH group (IMTmean: 0.91+/-0.02 mm; IMTmax: 1.03+/-0.02 mm) was significantly increased vs. the NG (IMTmean: 0.82+/-0.01 mm; IMTmax: 0.94+/-0.01 mm) and IFH group (IMTmean: 0.81+/-0.02 mm; IMTmax: 0.90+/-0.03 mm). IMT of the IFH group was similar to the normoglycemic controls. Subjects in the first and second tertile for postchallenge plasma glucose have similar carotid IMT irrespective of the level of fasting plasma glucose. The individuals of the third tertile for 2 h plasma glucose, whether in the first, second or third tertile of fasting plasma glucose, showed the same carotid IMT, which was significantly higher than all other groups, except for the one with lowest tertile for fasting and postchallenge plasma glucose. Except for total cholesterol and von Willebrand factor the levels of all other risk parameters were significantly higher in the hyperglycemic groups in comparison to the normoglycemic controls. Among the hyperglycemic subjects the CH group was at the highest risk for atherosclerosis with significantly increased levels of plasma triglycerides, fibrinogen, PAI-1, albuminuria, HDL-triglycerides, free fatty acids, insulin and proinsulin, and significantly reduced HDL-cholesterol in comparison to the normoglycemic controls. In summary, postchallenge hyperglycemia within the non-diabetic range is associated with atherosclerosis, as measured by the increased intima-media thickness of the common carotid artery. Furthermore, cardiovascular risk factors are significantly raised in all types of non-diabetic hyperglycemia.
 ...
PMID:Prevalence and atherosclerosis risk in different types of non-diabetic hyperglycemia. Is mild hyperglycemia an underestimated evil? 1082 15


<< Previous 1 2 3 4 5 Next >>