雌激素介导的HSP27在动脉粥样硬化中作用的研究进展

Research progress of estrogen-mediated HSP27 in atherosclerosis

热休克蛋白27(HSP27)是人体内一种在应激状态下大量表达的蛋白,其对机体一系列生理、病理过程有着重要作用。近年研究表明,雌激素通过多种途径调控HSP27的表达对动脉起到了完美的"三重保护"作用。血管内皮损伤早期雌激素通过PI3K/Akt信号通路诱导HSP27磷酸化,磷酸化的HSP27则通过抗氧化、调控凋亡通路、抑制细胞色素C(cyt-C)等作用,抵抗血管内皮细胞(VECs)凋亡;泡沫细胞形成期,雌激素通过刺激雌激素受体β(ERβ)诱导巨噬细胞表达和释放HSP27,后者则与巨噬细胞表面的清道夫受体A(SR-A)结合,阻止低密度脂蛋白(LDL)的摄取和促炎因子的释放;血管平滑肌细胞(VSMCs)增殖、迁移期,雌激素诱导雌激素受体α(ERα)与蛋白磷酸酶2(PP2A)形成复合物,增强PP2A的活性,引起下游HSP27脱磷酸,抑制VSMCs增殖、迁移。综上,雌激素抗动脉粥样硬化(atherosclerosis,AS)作用与HSP27密切相关,而雌激素替代疗法(MHT)防治绝经女性心血管疾病的副作用不容小觑,故借鉴雌激素的调控机制,研发药物调控HSP27对防治AS有着重要意义。

Heat shock protein 27(HSP27) is an endogenous protein that plays an important role in a great variety of physiological and pathological processes.It can express a large number under body stress conditions.Recent studies have shown estrogen upregulates the expression of HSP27 through a number of ways,playing a perfect 'triple protection' role.In the early stage of atherosclerosis,estrogen induces the phosphorylation of HSP27 via PI3K/Akt signaling pathway.Phosphorylation of HSP27 can resist the injury of vascular endothelial cells(VECs)through an antioxidant and anti-apoptotic pathway as well as the inhibition of cytochrome C.In the stage of forming foam cells,estrogen induces the expression and release of HSP27 from macrophages by stimulating the estrogen receptor β(ERβ),then HSP27 inhibits the LDL uptake and the release of proinflammatory cytokine by binding scavenger receptor A(SR-A).During the proliferation and migration of vascular smooth muscle cells(VSMCs),estrogen induces estrogen receptor α(ERα) and protein phosphatase 2(PP2A) to form a complex that enhances the activity of PP2 A,then it can lead to the dephosphorylation of HSP27 and finally inhibit cells proliferation and migration.In summary,the anti-atherosclerotic effect of estrogen is closely related to the role of HSP27.Given the side effects of estrogen replacement therapy(MHT),regulating HSP27 may provide a novel therapy for the prevention and treatment of cardiovascular diseases in menopausal women clinically.