Androgens inhibit tumor necrosis factor-伪-induced cell adhesion and promote tube formation of human coronary artery endothelial cells

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• 作者：Chun-Hou Liao^a ; ^b ; Feng-Yen Lin^c ; Yi-No Wu^b ; Han-Sun Chiang^a ; ^b ; ^{053824@mail.fju.edu.tw}
• 关键词：Androgen ; Atherosclerosis ; Endothelial cells ; HCAEC ; Testosterone
• 刊名：Steroids
• 出版年：2012
• 期刊代码：142_0039128x
• 类别：bio
• 出版时间：June, 2012
• 卷：77
• 期：7
• 页码：756-764
• 文件大小：1168 K

摘要

Endothelial cells contribute to the function and integrity of the vascular wall, and a functional aberration may lead to atherogenesis. There is increasing evidence on the atheroprotective role of androgens. Therefore, we studied the effect of the androgens鈥攖estosterone and dihydrotestosterone鈥攁nd estradiol on human coronary artery endothelial cell (HCAEC) function. We found by MTT assay that testosterone is not cytotoxic and enhances HCAEC proliferation. The effect of testosterone (10-50 nM), dihydrotestosterone (5-50 nM), and estradiol (0.1-0.4 nM) on the adhesion of tumor necrosis factor-伪 (TNF-伪)-stimulated HCAECs was determined at different time points (12-96 h) by assessing their binding with human monocytic THP-1 cells. In addition, the expression of adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1), was determined by ELISA and Western blot analysis. Both testosterone and dihydrotestosterone attenuated cell adhesion and the expression of VCAM-1 and ICAM-1 in a dose- and time-dependent manner. Furthermore, androgen treatment for a longer duration inhibited cell migration, as demonstrated by wound-healing assay, and promoted tube formation on a Matrigel. Western blot analysis demonstrated that the expression of phosphorylated endothelial nitric oxide synthase (eNOS) increased, whereas that of inducible nitric oxide synthase (iNOS) decreased following the 96-h steroid treatment of TNF-伪-stimulated HCAECs. Our findings suggest that androgens modulate endothelial cell functions by suppressing the inflammatory process and enhancing wound-healing and regenerative angiogenesis, possibly through an androgen receptor (AR)-dependent mechanism.