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)

Dehydroepiandrosterone sulfate (DHEAS) is an endogenous steroid having a wide variety of biological effects, but its physiological role remains undefined. Since an age-related decline of DHEAS corresponds to the progressive onset of atherosclerosis, cardiovascular diseases, and overall mortality, we investigated a possible protective role of DHEAS in vascular disease by studying the effects of this hormone (10(-7) to 10(-5) mol/L) on cytosolic free calcium and contractility in different in vitro vascular tissue preparations. DHEAS produced a significant, dose-dependent relaxation of isolated helical strips of rat tail artery precontracted with KCl (60 mmol/L) (89.7 +/- 18.7%, P < .01), arginine vasopressin (3 nmol/L) (27.3 +/- 7.1%, P < .01), and norepinephrine (0.1 mumol/L) (49.2 +/- 18.2%, P < .01). In isolated vascular smooth muscle cells DHEAS reversibly inhibited KCl (30 mmol/L)-induced elevations of cytosolic free calcium to 69.8 +/- 8.4% and 43.8 +/- 7.4% of the control response at 5 x 10(-7) and 5 x 10(-6) mol/L, respectively (P < .05 at both doses). These results provide evidence of a direct vascular action of DHEAS, in doses reflecting circulating levels in vivo, and suggest the possibility that these effects are mediated by modulation of intracellular calcium metabolism. We hypothesize that physiologically, DHEAS may serve to buffer vascular responsiveness to a wide variety of depolarizing and constrictor hormonal stimuli.
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PMID:Effects of dehydroepiandrosterone sulfate on cellular calcium responsiveness and vascular contractility. 749 69

Dehydroepiandrosterone sulfate (DHEA-S) is the most abundant circulating adrenal steroid in man, yet its physiologic role and that of its parent compound DHEA are unknown. Age-related decreases in DHEA in association with increases in obesity, insulin resistance, and atherosclerosis are well known. Recent investigations in lower mammals (which do not secrete DHEA) have suggested that DHEA (or its metabolites) may function as an antiobesity agent in these models of obesity independent of food intake. Proposed mechanisms for the decrease in fat mass and lower weight gain when DHEA is given orally include increases in futile cycling and peroxisomal beta-oxidation and decreases in de novo lipogenesis. Alterations in the availability of reducing equivalents for lipid synthesis do not appear to explain this decrease. Changes in pancreatic insulin secretion or insulin sensitivity may also be responsible for some of these effects. Studies in humans have failed to demonstrate a beneficial effect of DHEA on body composition or energy expenditure at either pharmacologic or physiologic replacement doses for 1-3 months. Administration of DHEA to men or women has also not been shown to alter insulin sensitivity as measured by the minimal model or the euglycemic clamp technique. The effect of DHEA on peroxisomal beta-oxidation and de novo lipogenesis is not known. We conclude that a significant role for DHEA in the pharmacologic treatment of human obesity is unlikely.
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PMID:Dehydroepiandrosterone and body fat. 869 65

The relationships between Dehydroepiandrosterone sulfate (DHEAS) level and atherosclerosis were studied using 90 men who received a general medical examination in their company. The mean serum DHEAS level was 1510.2 ng/ml, while the frequency distribution was skewed to a lower value. A marked linear decline of levels with age was observed. DHEAS levels were positively correlated with high density lipoprotein-cholesterol (HDLC) (r = 0.22, p < 0.05), and negatively correlated with low density lipoprotein-cholesterol (LDLC) (r = -0.31, p < 0.001), even after adjustment for age. The mean Atherogenic index (AI) was significant inversely correlated with rise of tertiles of the DHEAS level, both before and after adjustment for age, total cholesterol (TC), HDLC and triglyceride (TG). These results suggest that DHEAS may have an important role in the etiology and prevention of atherosclerosis.
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PMID:Relationship between dehydroepiandrosterone sulfate and serum lipid levels in Japanese men. 879 44

Dehydroepiandrosterone sulfate (DHEAS) is an adrenal steroid which has been inversely associated with development of atherosclerosis. We estimated heritability of serum DHEAS levels in 564 related Mexican Americans. We found a significant heritability for DHEAS (h2 = 0.39, p < 0.001). Measures of alcohol consumption, reproductive status, body composition, and HDL3 levels showed significant relationships with serum DHEAS levels. Sex and age were significantly associated with the mean, but not the genetic variance, of DHEAS levels. The results of this study demonstrate a significant genetic influence on steroid concentration and help to quantify the factors contributing to cardiovascular disease risk in Mexican Americans.
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PMID:Quantitative genetics of dehydroepiandrosterone sulfate and its relation to possible cardiovascular disease risk factors in Mexican Americans. 895 25

Dehydroepiandrosterone sulfate (DHEAS) is a major secretory product of the adrenal glands. DHEAS is inversely associated with death from cardiovascular disease in males, but not in females. This cross-sectional study examined the relationships between serum DHEAS levels and atherosclerosis in free living subjects in Japan. We measured the serum DHEAS levels of 990 apparently healthy subjects aged 35-81 years old in a rural area in Japan; 431 males and 559 females. The levels were determined by the radioimmunoassay method. The frequency distribution was skewed to a lower value in both sexes. Both unadjusted and age-adjusted mean DHEAS levels were statistically higher in males than in females, A marked linear decline of levels with age was observed in both sexes. DHEAS levels were positively correlated with high density lipoprotein-cholesterol (HDLC), and negatively correlated with low density lipoprotein-cholesterol (LDLC) even after adjustment for age in both sexes. The mean atherogenic index (AI) was significantly inversely correlated with the rise of tertiles of the DHEAS level, both before and after adjustment for age, Total cholesterol (TC), HDLC and Triglyceride (TG). These results suggest high levels of serum DHEAS may have an inhibitory effect on the development of atherosclerosis and have an important role in its etiology and prevention.
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PMID:Distribution of dehydroepiandrosterone sulfate and relationships between its level and serum lipid levels in a rural Japanese population. 988 78

Dehydroepiandrosterone sulfate (DHEAS) is a hormone produced by the adrenal gland and is a precursor for both androgens and estrogens. Atherosclerosis is a well characterized inflammatory disease, but little is known about the role of DHEAS in vascular inflammation. We hypothesize that DHEAS can reduce inflammation in vascular endothelial cells and the mechanism involves the peroxisome proliferator-activated receptor alpha (PPARalpha), thereby inhibiting transcription factors involved in endothelial cell inflammation. To test our hypothesis, aortic endothelial cells were pretreated for 48 h with DHEAS, then with TNF-alpha. TNF-alpha-induced upregulation of the expression of inflammatory genes interleukin (IL)-8 and intracellular adhesion molecule (ICAM)-1 was attenuated by incubation with DHEAS. DHEAS inhibited the TNF-alpha-induced surface expression of vascular cell adhesion molecule (VCAM)-1. This effect was abolished by the addition of MK866, a PPARalpha inhibitor, indicating that PPARalpha is involved in the mechanism of this inhibition. The addition of the aromatase inhibitor letrozole had no effect on the inhibition of TNF-alpha-induced VCAM-1 expression by DHEAS. Treatment of endothelial cells with DHEAS dramatically inhibited the TNF-alpha-induced activation of NF-kappaB, an inflammatory transcription factor, and increased protein levels of the NF-kappaB inhibitor, IkappaB-alpha. These results signify the ability of DHEAS to directly inhibit the inflammatory process and show a potential direct effect of DHEAS on vascular inflammation that has implications for the development of atherosclerotic cardiovascular disease.
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PMID:Inhibition of vascular inflammation by dehydroepiandrosterone sulfate in human aortic endothelial cells: roles of PPARalpha and NF-kappaB. 1825 43