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

Tumor necrosis factor (TNF) is an important cytokine in the inflammation process of atherosclerosis and is also involved in lipid metabolism. Two biallelic polymorphisms within TNF gene locus-TNFA at the position -308 in the promoter region of the TNF gene and TNFB in the first intron of the lymphotoxin-alpha (LT-alpha) have been reported to be associated with TNF production and with susceptibility to inflammatory diseases. We studied the association of these polymorphisms within the major histocompatibility complex (MHC) III region with coronary atherosclerosis and its manifestations. The autopsy series comprised 700 Caucasian Finnish men, aged 33-70 years (The Helsinki Sudden Death Study). Coronary stenosis and surface area of atherosclerotic changes (fatty streaks, fibrous plaques, complicated lesions and calcification) were measured and the presence of myocardial infarction and coronary thrombosis recorded. TNFA and TNFB genotypes were determined by the PCR-RFLP technique. The allele frequencies were TNFA1/TNFA2=0.88/0.12 and TNFB1/TNFB2=0.30/0.70. There was a strong linkage disequilibrium between the two polymorphisms. There were no differences in coronary stenosis and in the frequency of old or recent myocardial infarction or coronary thrombosis between men with different genotype status in either locus. Men with TNFA22 or TNFB11 genotype tended to have more fibrous lesions and calcification in their coronary arteries. TNFA and TNFB polymorphisms are unlikely to contribute to progression of atherosclerosis in a way clinically important.
Atherosclerosis 2001 Feb 15
PMID:Polymorphisms within the tumor necrosis factor locus and prevalence of coronary artery disease in middle-aged men. 1125 71

Obesity is related to cardiovascular disease (CVD) morbidity and mortality, however, the mechanisms for the development of obesity-induced CVD risk remain unclear. Hyperinsulinemia and insulin resistance are considered key components in the metabolic cardiovascular syndrome and as independent risk factors for CVD. Plasma leptin and tumor necrosis factor-alpha (TNF-alpha), two adipocyte products, are also proposed to be associated with the development of CVD risk. The purpose of this study is to evaluate the association of plasma leptin, soluble TNF receptors (sTNF-R), and insulin levels as possible mediators of the effect of obesity on atherogenic and thrombogenic CVD risk factors among men. From the Health Professionals Follow-up Study (HPFS), we selected 268 men, aged 47--83 years, who were free of CVD, diabetes, and cancer (except non-melanoma skin cancer), and who had provided a fasting blood sample in 1994. We measured plasma insulin and leptin levels by radioimmunoassay and sTNF-R levels by ELISA. Men in the highest quintile of body mass index (BMI, mean=30.5 kg/m(2)) were less physically active and had a more adverse cardiovascular lipid and homeostatic profile, as indicated by levels of insulin, triglyceride (TG), tissue plasminogen activator (t-PA) antigen levels, and apolipoprotein A1 (Apo-A1). In a multivariate regression model controlling for age, smoking, alcohol intake, physical activity and diet, BMI was inversely associated with HDL-cholesterol (HDL-C) and Apo-A1 and positively associated with TG, Apo-B and t-PA antigen levels. The associations between BMI and these CVD risk factors were only slightly changed after adjusting for leptin and/or sTNF-R; but were substantially attenuated after controlling for insulin levels. These data suggest that the association between obesity and biological predictors of CVD may be mediated through changes in plasma insulin, rather than leptin or sTNF-R levels. However, plasma leptin may still play a role in CVD through independent effects on lipid metabolism.
Atherosclerosis 2001 Aug
PMID:Plasma insulin, leptin, and soluble TNF receptors levels in relation to obesity-related atherogenic and thrombogenic cardiovascular disease risk factors among men. 1147 52

Men have an earlier onset and higher incidence of coronary heart disease than women, independent of environmental risk factor exposure. As a consequence, there has been considerable interest in the potential role of sex hormones in atherogenesis. An emerging body of evidence suggests that sex-specific tissue and cellular characteristics may mediate sex-specific responses to a variety of stimuli. Recent studies have shown that oestrogen, progesterone and androgens all regulate processes integral to human macrophage foam cell formation, a key event in atherogenesis, in a sex-specific manner; findings that may have important implications for understanding the sex gap in atherosclerosis. Physiological levels of 17beta-estradiol and progesterone are both associated with a female-specific reduction in cholesteryl ester accumulation in human macrophages. By contrast, androgens increase cholesteryl ester formation in male but not in female donor human macrophages. This review summarizes current data concerning the sex-specific effects of sex hormones on processes important to macrophage foam cell formation and the basic mechanisms responsible for the sex specificity of such effects. Future research in this promising field may eventually lead to the novel concept of 'sex-specific' treatments directed at inhibiting atherogenesis.
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PMID:Sex-related differences in the regulation of macrophage cholesterol metabolism. 1156 Nov 69

A rather common leucine7-to-proline7 (Leu7Pro) polymorphism in the preproneuropeptide Y (prepro-NPY) gene signal peptide may be important in blood pressure regulation, cholesterol metabolism and the pathogenesis of atherosclerosis in humans. We examined the associations of the Leu7Pro polymorphism with carotid atherosclerotic progression, blood pressure and serum lipids in a population-based sample of 966 men aged 42-60 years in Finland. The Pro7 substitution (carrier frequency 12.2%) was associated with accelerated four-year increase in the mean (P=0.01) and maximal (P=0.007) common carotid intima-media thickness (IMT) and with slightly increased systolic (P=0.03) and diastolic (P=0.02) blood pressures, adjusted for other major risk factors. Men with Pro7 substitution had 30.6% (95% CI 6.9-54.0%) greater increase in the mean IMT and 20.0% (95% CI 5.3-34.4%) greater increase in the maximal IMT than men with Leu7/Leu7 genotype. The Pro7 substitution was also related to increased serum total cholesterol (P=0.01) and LDL cholesterol (P=0.02) in obese (body mass index (BMI)>30 kg/m(2)) men. This study provides important evidence suggesting that the Pro7 substitution in the prepro-NPY is an important risk factor for accelerated atherosclerotic progression, increased blood pressure and increased serum cholesterol in humans.
Atherosclerosis 2001 Nov
PMID:Leucine7 to proline7 polymorphism in the preproneuropeptide Y is associated with the progression of carotid atherosclerosis, blood pressure and serum lipids in Finnish men. 1168 16

Quantifying the severity of adrenocortical nodular hyperplasia at autopsy or surgery has much potential practical value. For instance, this inquiry explores the correlation of adrenal nodularity with features of atherosclerosis in coronary arteries and microvascular features of hypertension in the renal cortex. Tissue retrieved from forensic autopsies in 96 men and women ages 16 to 88 years were evaluated for adrenal nodularity, coronary atheroma, and hypertensive renal microvasculopathies. Formalin-fixed adrenal glands were cut into 0.5-cm thick slices and fixed to plastic sheets with SuperGlue (Ross Products, Inc, Columbus, OH). After ranking the specimens on increasing nodularity, they were judged to fall into 10 distinguishable grades of increasing severity; photographs of a representative in each grade were arranged onto a panel. Each gland was then assigned the grade of the photograph it most resembled. Coronaries and kidneys were evaluated in paraffin sections. Weight and nodularity of adrenal glands increased with age. Men with at least one instance of atheroma in the coronary sample had heavier and more nodular glands (age-adjusted) than in men without atheroma. The differences held stronger statistical significance for nodularity than for weight because nodularity continued to show significance even within age groups sometimes represented by few cases. Hypertensive renal microvasculopathies failed to correlate with any of the adrenal features. Women were too few for the analysis. Findings made with the panel of photographs now available for grading adrenocortical nodular hyperplasia showed interesting correlations with coronary atherosclerosis in this data set, suggesting that use of this method might offer some insight into cardiovascular disease.
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PMID:A method for quantifying adrenocortical nodular hyperplasia at autopsy: some use of the method in illuminating hypertension and atherosclerosis. 1184 76

A reduced expression of the insulin resistance syndrome, a common neuroendocrine disorder underlying atherosclerosis, may play a role in reduced atherosclerosis in adults with Down syndrome. We compared selected components of the insulin resistance syndrome between 75 adults with Down syndrome and 70 with mental retardation due to other causes. After adjusting for age differences, residence, cigarette smoking, and medication use, women with Down syndrome had lower fasting plasma glucose and lower systolic blood pressure than comparison women. Men with Down syndrome had lower systolic and diastolic blood pressure than comparison men. Results suggest that women with Down syndrome may be less likely to express the insulin resistance syndrome, and men and women with Down syndrome may possess fewer atherosclerotic risk factors than the comparison groups.
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PMID:Differences in cardiovascular disease risk between nondiabetic adults with mental retardation with and without Down syndrome. 1196 33

Several studies have shown that low birthweight is associated with a higher risk of stroke and coronary heart disease in later life. Increased atherogenesis may be one underlying mechanism, but few studies have examined this directly. We used duplex ultrasonography to assess the extra-cranial carotid arteries of 389 elderly men and women born and still living in Sheffield, UK, whose recorded birth measurements were available. Men and women who had weighed 6.5 lbs or less at birth had a higher risk of having carotid stenosis >30% than those who weighed over 7.5 lbs, but this trend was not statistically significant (OR 1.8, 95% CI 1.0-3.3). Women who had been lighter or who had a smaller head circumference at birth tended to have an increased intima-media thickness, but these relations ceased to be statistically significant after adjustment for gestational age and cardiovascular risk factors. In men, by contrast, an increased intima-media thickness was associated with having been heavier at birth (P=0.049) or having had a larger abdominal circumference at birth (P=0.040), after adjustment for gestational age and cardiovascular risk factors. These results provide little evidence that impaired fetal growth increases susceptibility to atherogenesis.
Atherosclerosis 2002 Jul
PMID:Size at birth and carotid atherosclerosis in later life. 1204 32

In both men and women, circulating androgen levels decline with advancing age. Until now, results of several small studies on the relationship between endogenous androgen levels and atherosclerosis have been inconsistent. In the population-based Rotterdam Study, we investigated the association of levels of dehydroepiandrosterone sulfate (DHEAS) and total and bioavailable testosterone with aortic atherosclerosis among 1,032 nonsmoking men and women aged 55 yr and over. Aortic atherosclerosis was assessed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. Relative to men with levels of total and bioavailable testosterone in the lowest tertile, men with levels of these hormones in the highest tertile had age-adjusted relative risks of 0.4 [95% confidence interval (CI), 0.2-0.9] and 0.2 (CI, 0.1-0.7), respectively, for the presence of severe aortic atherosclerosis. The corresponding relative risks for women were 3.7 (CI, 1.2-11.6) and 2.3 (CI, 0.7-7.8). Additional adjustment for cardiovascular disease risk factors did not materially affect the results in men, whereas in women the associations diluted. Men with levels of total and bioavailable testosterone in subsequent tertiles were also protected against progression of aortic atherosclerosis measured after 6.5 yr (SD +/- 0.5 yr) of follow-up (P for trend = 0.02). No clear association between levels of DHEAS and presence of severe aortic atherosclerosis was found, either in men or in women. In men, a protective effect of higher levels of DHEAS against progression of aortic atherosclerosis was suggested, but the corresponding test for trend did not reach statistical significance. In conclusion, we found an independent inverse association between levels of testosterone and aortic atherosclerosis in men. In women, positive associations between levels of testosterone and aortic atherosclerosis were largely due to adverse cardiovascular disease risk factors.
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PMID:Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. 1262 41

Nitric oxide (NO), formed by endothelial constitutive nitric oxide synthase (eNOS) maintains endothelium-dependent vasodilatation and also mediates antithrombotic actions. The eNOS gene harbours a common polymorphism in intron 4 (4a/b), and some clinical studies have suggested an association of the rare a-allele with coronary artery disease (CAD) and myocardial infarction (MI). However, contradictory results have also been reported. We studied associations of eNOS polymorphism with CAD and MI in two prospective autopsy series comprising altogether 700 Caucasian Finnish men, who died suddenly. In ANCOVA, no significant differences in areas of atherosclerotic lesions and coronary stenosis percentages were found between men carrying the a-allele (ba+aa) compared with those homozygous for the b-allele. Subjects with the a-allele had significantly lower risk of MI (odds ratio 0.44, 95% confidence interval 0.25-0.77, P=0.004) compared with those carrying the bb genotype. Men with the a-allele also tended to have coronary thrombosis less often (odds ratio 0.43, 95% confidence interval 0.18-1.01, P=0.055). The eNOS gene 4a/b polymorphism was not associated with the extent of coronary atherosclerosis, but the a-allele of the variant seems to protect to some degree against the development of MI.
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PMID:Association of the endothelial nitric oxide synthase gene polymorphism with risk of coronary artery disease and myocardial infarction in middle-aged men. 1222 42

Cardiovascular disease, in particular coronary artery disease (CAD), remains the most important cause of morbidity and mortality in developed countries and, in the near future, more so in the developing world. Atherosclerotic plaque formation is the underlying basis for CAD. Growth of the plaque leads to coronary stenosis, causing a progressive decrease in blood flow that results in angina pectoris. Acute myocardial infarction and unstable angina were recently recognised as related to plaque rupture, not progressive coronary stenosis. Acute thrombus formation causes an abrupt coronary occlusion. The characteristics of the fibrin cap, contents of the plaque, rheological factors and active inflammation within the plaque contribute to plaque rupture. Oxidative processes are important in plaque formation. Oxidized low density lipoproteins (LDL) but not unoxidized LDL is engulfed by resident intimal macrophages, transforming them into foam cells which develop into fatty streaks, the precursors of the atherosclerotic plaque. Inflammation is important both in plaque formation and rupture. Animal studies have shown that antioxidants reduce plaque formation and lead to plaque stabilisation. In humans, high intakes of antioxidants are associated with lower incidence of CAD, despite high serum cholesterol levels. This observation suggests a role for inflammation in CAD and that reducing inflammation using antioxidants may ameliorate these processes. Men and women with high intakes of vitamin E were found to have less CAD. Vitamin E supplementation was associated with a significant reduction in myocardial infarction and cardiovascular events in the incidence of recurrent myocardial infarction. In the hierarchy of evidence in evidence-based medicine, data from large placebo-controlled clinical trials is considered necessary. Results from various mega-trials have not shown benefits (nor adverse effects) conferred by vitamin E supplementation, suggesting that vitamin E has no role in the treatment of CAD. These results do not seem to confirm, at the clinical level, the effect of antioxidants against active inflammation during plaque rupture. However, a closer examination of these studies showed a number of limitations, rendering them inconclusive in addressing the role of vitamin E in CAD prevention and treatment. Further studies that specifically address the issue of vitamin E in the pathogenesis of atherosclerosis and in the treatment of CAD need be performed. These studies should use the more potent antioxidant property of alpha-tocotrienol vitamin E.
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PMID:Vitamin E in cardiovascular disease: has the die been cast? 1249 32


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