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.
ABSTRACT
Objective:To investigate the influence of Xuefu Zhuyu Decoction ( XZD) contained Drug-Serum on the expression of TLR4/NF-κB signals and LOX-1, TNF-α, ICAM-1, VCAM-1 in HUVECs, and to study its possible anti-atherosclerotic mechanism.Methods:HUVECs was cultured in vitro and divided equally into the normal group ,the model group,the ATV group and the XZD group in random.HUVECs were stimulated with LPS for 2 h,then treated separately with the drug-serum and atorvastatin for 24 h,finally measured the expression of TLR 4, MyD88, TRAF-6, NF-κB, LOX-1, TNF-α, ICAM-1 and VCAM-1 mRNA with real-time PCR,the expression of TLR4,NF-κB,LOX-1,TNF-α,ICAM-1 and VCAM-1 protein were analyzed by Western blot method .Results:Protein and mRNA expressions of TLR4,MyD88,TRAF-6,NF-κB,LOX-1,TNF-α,ICAM-1 and VCAM-1 increased significantly after LPS stimulation(vs normal control group,P<0.01),Xuefu Zhuyu Decoction decreased the high expression of TLR 4,MyD88,TRAF-6, NF-κB,LOX-1,TNF-α,ICAM-1 and VCAM-1(vs model group,P<0.05 ).Conclusion:Xuefu Zhuyu Decoction can block the high ex-pression of TLR4 and its downstream signal transduction pathway and the high expression of LOX -1, TNF-α, ICAM-1 and VCAM-1.Maybe it′s the mechanism of Xuefu Zhuyu Decoction exert the function of anti-artherosclerosis.