The Role Of MYl9 In The Progression Of Atherosclerosis

Atherosclerosis and its caused by coronary heart disease,hypertension and other important diseases that endanger human health.After arterial injury,smooth muscle cells,macrophages,damaged endothelial cells release a large number of growth factors.Inflammation plays an important role in the occurrence and development of many cardiovascular diseases such as atherosclerosis,heart failure,cardiomyopathy and aneurysm.Inflammation is the first step in the process of vulnerability and rupture of plaque.Inflammation can induce the secretion of many factors,such as Angiotensin II(AngII)and platelet-derived growth factor(PDGF),which can promote inflammation and fibrosis of cytokines,promote vascular injury.These factors and their corresponding receptors,activate Akt / mTOR and other signaling pathways,promote smooth muscle cell proliferation,migration and invasion,affecting the occurrence and development of atherosclerotic plaque.Rapamycin is a class of ma crolide antibiotics with antiproliferative effects.The initial study was used to inhibit the immune response after organ transplantation.Rapamycin significantly inhibited the proliferation and migration of vascular smooth muscle cells.MYL9 is an important part of the cytoskeleton.Stimulation of Angiotensin II and platelet-derived growth factor activates myosin light chain muscle enzyme activity and activates Akt / mTOR signaling,but the role and mechanism of MYL9 in atherosclerosis remains to be studied.Purpose: MYL9 expression in atherosclerosis regulation and its direct cardiovascular effects are not clear.This study aimed to detect the MYL9 expression in atherosclerosis and the clinical anti-restenosis drug rapamycin(Rapamycin)MYL9 expression regulation of MYL9 in atherosclerosis and explore the possible role The mechanism of action.Methods and Results: Immunohistochemistry,Western blot and RT-PCR showed that in the model of atherosclerosis,the expression of MYL9 in blood vessel was significantly decreased with the increase of plaque.The level of atherosclerosis IV was significantly lower in MYL9 than in normal coronary arteries.The results of RT-PCR and Western blot showed that the expression of MYL9 in vascular smooth muscle cells was down-regulated by Angiotension II and PDGF-BB in cultured vascular smooth muscle cells.Western blot analysis showed that the scaffold-coated drug rapamycin up-regulated MYL9 expression in a dose-dependent manner.In vascular smooth muscle cells,the expression of MYL9 was decreased in angiotensin II group compared with that in normal group,but there was almost no change in total mTOR and Akt,but the phosphorylation of mTOR,Akt and PCNA were increased.In rapamycin group,MYL9 expression increased,total mTOR and Akt almost unchanged,but the phosphorylation of mTOR,Akt and PCNA expression was significantly reduced.siRNA-mediated knockdown of MYL9 significantly stimulated the proliferation and migration of vascular smooth muscle cells.The results of Transwell and scratch-wound assay showed that the proliferation and migration of vascular smooth muscle cells in VSMCs treated with Akt / mTOR pathway inhibitor PI-103 and si RNA groups were decreased compared with siRNA group.Conclusions: Our results suggest that MYL9 may be an important regulator of atherosclerosis.MYL9 is a new target of rapamycin in vascular smooth muscle cells.Our results suggest that MYL9 may be a potential therapeutic target for clinically vascular proliferative diseases such as atherosclerosis.