Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells.
Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells.
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DOI：
10.1152/ajpendo.00693.2009
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发表时间：
2010-04
期刊：
影响因子：
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通讯作者：
K. Osterlund;R. Handa;R. Gonzales
中科院分区：
文献类型：
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作者：
K. Osterlund;R. Handa;R. Gonzales
雄激素对心血管系统的保护性和非保护性作用都有报道。我们以前的研究表明，强有力的雄激素受体（AR）激动剂双氢睾酮（DHT）增加的血管炎症介质环氧合酶（考克斯）-2（COX-2）在啮齿动物脑动脉的水平独立于炎症刺激。关于雄激素对人类血管组织炎症的影响知之甚少。因此，我们测试了假设，即DHT改变考克斯-2水平的情况下，存在或不存在诱导的炎症原代人冠状动脉平滑肌细胞（HCASMC）。此外，我们还检验了辅助假设，即DHT对考克斯-2水平的影响是AR依赖性的。在存在或不存在LPS或IL-1 β的情况下，用DHT（10 nM）或溶媒处理细胞6 h。与先前在啮齿类动物动脉中的观察结果相似，在HCASMC中，与溶媒相比，单独的DHT增加了考克斯-2水平。在AR拮抗剂比卡鲁胺的存在下，DHT的这种作用减弱。相反，在LPS或IL-1 β存在的情况下，考克斯-2的增加通过与DHT共同处理而减弱。比卡鲁胺不影响这种反应，表明DHT诱导的考克斯-2水平降低与AR刺激无关。因此，我们得出结论，DHT差异影响考克斯-2水平下的生理和病理生理条件下，在HCASMC。DHT对考克斯-2的这种作用涉及AR依赖性和非依赖性机制，这取决于细胞的生理状态。
Both protective and nonprotective effects of androgens on the cardiovascular system have been reported. Our previous studies show that the potent androgen receptor (AR) agonist dihydrotestosterone (DHT) increases levels of the vascular inflammatory mediator cyclooxygenase (COX)-2 in rodent cerebral arteries independent of an inflammatory stimulus. Little is known about the effects of androgens on inflammation in human vascular tissues. Therefore, we tested the hypothesis that DHT alters COX-2 levels in the absence and presence of induced inflammation in primary human coronary artery smooth muscle cells (HCASMC). Furthermore, we tested the ancillary hypothesis that DHT's effects on COX-2 levels are AR-dependent. Cells were treated with DHT (10 nM) or vehicle for 6 h in the presence or absence of LPS or IL-1beta. Similar to previous observations in rodent arteries, in HCASMC, DHT alone increased COX-2 levels compared with vehicle. This effect of DHT was attenuated in the presence of the AR antagonist bicalutamide. Conversely, in the presence of LPS or IL-1beta, increases in COX-2 were attenuated by cotreatment with DHT. Bicalutamide did not affect this response, suggesting that DHT-induced decreases in COX-2 levels occur independent of AR stimulation. Thus we conclude that DHT differentially influences COX-2 levels under physiological and pathophysiological conditions in HCASMC. This effect of DHT on COX-2 involves AR-dependent and- independent mechanisms, depending on the physiological state of the cell.