Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon.
Department of Biology, American University of Beirut, Beirut, Lebanon.
Vascul Pharmacol. 2018 Dec;111:15-21. doi: 10.1016/j.vph.2018.09.001. Epub 2018 Sep 15.
Cardiovascular disease (CVD) continues to be the leading cause of death worldwide. The effect of estrogen on these diseases has been assessed in in vitro and in vivo models, as well as in observational studies. Collectively, these studies alluded to a cardiovasculo-protective effect of estrogen. However, comprehensive clinical investigation failed to produce concrete proof of a cardiovascular protective effect for hormone replacement therapy (HRT), let alone rule out potential harm. These seemingly paradoxical effects of estrogen were explained by the 'theory of timing and opportunity'. This theory states that the effect of estrogen, whether cardiovasculo-protective or pathological, significantly depends on the age of the individual when estrogen administration takes place. Here, we review the conflicting effects of estrogen on vascular smooth muscle cells, mainly proliferation and migration as two cellular capacities intimately related to physiology and pathophysiology of the cardiovascular system. Furthermore, we critically discuss the major parameters and signaling pathways that may account for the aforementioned paradoxical observations, as well as the key molecular players involved.
心血管疾病（CVD）仍然是全球范围内的主要死亡原因。雌激素对这些疾病的影响已经在体外和体内模型以及观察性研究中进行了评估。这些研究都暗示了雌激素对心血管有保护作用。然而，全面的临床研究未能为激素替代疗法（HRT）提供具体的心血管保护作用的证据，更不用说排除潜在的危害了。这些雌激素看似矛盾的作用可以用“时间和机会理论”来解释。该理论指出，雌激素的作用，无论是心血管保护还是病理性的，都显著取决于个体接受雌激素治疗时的年龄。在这里，我们回顾了雌激素对血管平滑肌细胞的矛盾作用，主要是增殖和迁移，这两种细胞功能与心血管系统的生理和病理生理学密切相关。此外，我们还批判性地讨论了可能导致上述矛盾观察结果的主要参数和信号通路，以及涉及的关键分子。
