Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thromboxane A2 (TXA2), a platelet aggregator and vasoconstrictor, has been implicated as a potential pathophysiologic mediator of a wide variety of cardiovascular diseases. It is well established that men are at greater risk for cardiovascular disease compared to premenopausal females. Abuse of androgenic/anabolic steroids has been associated with thrombotic cardiovascular diseases in young male athletes. These observations along with several others have led to the hypothesis that testosterone may regulate the expression of TXA2 receptors. Rat aortic smooth muscle cells (RASMC) and human erythroleukemia cells (HEL), a megakaryocyte-like cell, were incubated with testosterone. TXA2 receptor affinity (Kd) and density (Bmax) were determined via equilibrium binding experiments using the radiolabeled TXA2 mimetic [125I]-BOP. Testosterone significantly increased the Bmax without any significant change in Kd. Hydroxyflutamide (1 microM), an androgen receptor antagonist, completely blocked the effect of testosterone. Dihydrotestosterone, the active metabolite of testosterone also increased Bmax in a concentration-dependent manner and was more potent than testosterone. These observations along with several others are consistent with the notion that androgenic steroids may regulate the expression of functional TXA2 receptors in HEL and RASMC. These results raise the possibility that the increase in TXA2 receptor density induced by testosterone may contribute to its thrombotic potential in cardiovascular diseases.
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PMID:The Gordon Wilson Lecture. Regulation of thromboxane A2 receptors by testosterone: implications for steroid abuse and cardiovascular disease. 797 82

Thromboxane A2 (TxA2), a platelet aggregator and vasoconstrictor, has been implicated as a potential mediator of cardiovascular diseases. Abuse of androgenic steroids has been associated with thrombotic cardiovascular diseases. Human erythroleukemia (HEL) cells, a megakaryocyte-like cell line, express functional TxA2/prostaglandin H2 (PGH2) receptors with characteristics similar to those seen in platelets. This study characterized testosterone regulation of HEL cell TxA2/PGH2 receptors. TxA2/PGH2 receptor affinity (Kd) and density (Bmax) were determined via equilibrium binding experiments using the radiolabeled TxA2 mimetic (1S-[1 alpha,2 beta(5Z),3 alpha(1E,3R*),4 alpha])-7-(3-[3-hydroxy-4-(4'- iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]heptan-2-yl)-5-he ptenoic acid (125I-labeled BOP). Testosterone (200 nM) but not estradiol increased Bmax from 108 +/- 9 fmol/mg protein to 157 +/- 9 fmol/mg protein (n = 7 experiments; P < 0.01) without any significant change in Kd. Testosterone had no significant effect on alpha 2-adrenergic receptor density. The maximum increase in intracellular free calcium induced by the TxA2 agonists I-BOP or U-46619 was significantly (P < 0.005) greater in testosterone-treated cells compared with controls. Hydroxyflutamide (1 microM), an androgen-receptor antagonist, completely blocked the effect of testosterone (P < 0.01). Dihydrotestosterone, the active metabolite of testosterone, also increased Bmax in a concentration-dependent manner and was more potent than testosterone. The effect of testosterone to increase Bmax was significantly (P < 0.01) inhibited by coincubation with cycloheximide (0.1 microgram/ml) or actinomycin D (10 ng/ml). These results indicate that androgenic steroids regulate the expression of functional TxA2/PGH2 receptors in HEL cells. These findings may have relevance to cardiovascular disease.
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PMID:Androgen regulation of thromboxane A2/prostaglandin H2 receptor expression in human erythroleukemia cells. 827 49