Chakrabarti Subhadeep, Lekontseva Olga, Davidge Sandra T
Department of Obstetrics and Gynecology, Perinatal Research Centre and Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada.
IUBMB Life. 2008 Jun;60(6):376-82. doi: 10.1002/iub.48.
Vascular inflammation underlies the pathogenesis of atherosclerosis. Atherosclerotic changes in the vasculature lead to conditions such as coronary artery disease and stroke, which are the major causes of morbidity and mortality worldwide. Epidemiological studies in premenopausal women suggest a beneficial role for estrogen in preventing vascular inflammation and consequent atherosclerosis. However, the benefits of estrogen areabsent or even reversed in older postmenopausal subjects. The modulation of inflammation by estrogen under different conditions might explain this discrepancy. Estrogen exerts its antiinflammatory effects on the vasculature through different mechanisms such as direct antioxidant effect, generation of nitric oxide, prevention of apoptosis in vascular cells and suppression of cytokines and the renin-angiotensin system. On the other hand, estrogen also elicits proinflammatory changes under certain conditions, which are less completely understood. Some of the mechanisms underlying a possible proinflammatory role for estrogen include increased expression of the proinflammatory receptor for advanced glycation end products, increased tyrosine nitration of cellular proteins, and generation of reactive oxygen species through an uncoupled eNOS. In this review, we have presented evidence for both antiinflammatory and proinflammatory pathways modulated by estrogen and how interactions among such pathways might determine the effects of estrogen on the vascular system.
血管炎症是动脉粥样硬化发病机制的基础。血管的动脉粥样硬化变化会导致诸如冠状动脉疾病和中风等病症，而这些病症是全球发病和死亡的主要原因。对绝经前女性的流行病学研究表明，雌激素在预防血管炎症及随之而来的动脉粥样硬化方面具有有益作用。然而，在绝经后的老年受试者中，雌激素的益处并不存在，甚至会逆转。雌激素在不同条件下对炎症的调节可能解释了这种差异。雌激素通过不同机制对血管发挥抗炎作用，如直接抗氧化作用、一氧化氮的生成、预防血管细胞凋亡以及抑制细胞因子和肾素 - 血管紧张素系统。另一方面，雌激素在某些条件下也会引发促炎变化，而对这些变化的了解还不够全面。雌激素可能发挥促炎作用的一些潜在机制包括晚期糖基化终产物促炎受体表达增加、细胞蛋白酪氨酸硝化增加以及通过解偶联的内皮型一氧化氮合酶产生活性氧。在本综述中，我们展示了雌激素调节的抗炎和促炎途径的证据，以及这些途径之间的相互作用如何可能决定雌激素对血管系统的影响。
