Heart Research Institute, Sydney 2042, Australia.
J Exp Med. 2010 Feb 15;207(2):345-52. doi: 10.1084/jem.20091924. Epub 2010 Jan 13.
Mounting evidence suggests that in men, serum levels of testosterone are negatively correlated to cardiovascular and all-cause mortality. We studied the role of androgens in angiogenesis, a process critical in cardiovascular repair/regeneration, in males and females. Androgen exposure augmented key angiogenic events in vitro. Strikingly, this occurred in male but not female endothelial cells (ECs). Androgen receptor (AR) antagonism or gene knockdown abrogated these effects in male ECs. Overexpression of AR in female ECs conferred androgen sensitivity with respect to angiogenesis. In vivo, castration dramatically reduced neovascularization of Matrigel plugs. Androgen treatment fully reversed this effect in male mice but had no effect in female mice. Furthermore, orchidectomy impaired blood-flow recovery from hindlimb ischemia, a finding rescued by androgen treatment. Our findings suggest that endogenous androgens modulate angiogenesis in a sex-dependent manner, with implications for the role of androgen replacement in men.
越来越多的证据表明，在男性中，血清睾酮水平与心血管疾病和全因死亡率呈负相关。我们研究了雄激素在血管生成中的作用，血管生成是心血管修复/再生过程中的一个关键过程，在男性和女性中都有研究。雄激素暴露增强了体外关键的血管生成事件。引人注目的是，这种作用仅发生在雄性内皮细胞（ECs）中，而不是雌性 ECs 中。雄激素受体（AR）拮抗剂或基因敲低可阻断雄性 ECs 的这些作用。在雌性 ECs 中过表达 AR 可使 AR 对血管生成具有敏感性。在体内，去势可显著减少 Matrigel 塞子的新生血管形成。雄激素治疗可完全逆转雄性小鼠的这种作用，但对雌性小鼠无影响。此外，去势可损害后肢缺血血流恢复，雄激素治疗可挽救这一发现。我们的研究结果表明，内源性雄激素以性别依赖的方式调节血管生成，这对男性雄激素替代治疗的作用具有重要意义。
