Research progress of estrogen-mediated HSP27 in atherosclerosis / 中国药理学通报

ABSTRACT

Heat shock protein 27 ( HSP27 ) is an endogenous protein that plays an important role in a great variety of physio-logical and pathological processes. It can express a large number under body stress conditions. Recent studies have shown estro-gen 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 mac-rophages by stimulating the estrogen receptor β ( ERβ) , then HSP27 inhibits the LDL uptake and the release of proinflammato-ry 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 PP2A, 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 re-lated to the role of HSP27. Given the side effects of estrogen re-placement therapy( MHT) , regulating HSP27 may provide a no-vel therapy for the prevention and treatment of cardiovascular dis-eases in menopausal women clinically.