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Atherosclerosis(AS)is the primary cause leading to cardiovascular disease,the number of annual deaths due to AS-related diseases account for more than half of total global deaths.Exploring the pathogenesis of AS has a great significance for prevention and treatment of cardiovascular and cerebrovascular diseases.Myosin light chain kinase(MLCK)is a key enzyme in the regulation of vascular smooth muscle cells(VSMCs)contraction.MLCK inhibition can protect blood vessels and reduce the formation of AS plaque.However,the mechanism of the proliferation and migration of VSMCs regulated by MLCK is not clear during AS formation.Recent studies suggest that microRNAs play a key role in the regulation of function and plasticity of VSMCs.This study aims to explore the miRNAs related to the MLCK-incuced AS vascular remodeling and its mechanism by building atherosclerotic mouse models and culturing VSMCs and MLCK knockdown type VSMC(MLCK-/VSMC).Results: 1.In AS mouse model: In high-fat diet group,the vessel walls had no significant change in the third to the 6th weeks.The walls were thickened in 9th weeks with a small volume aortic plaque.The atherosclerotic plaques were completed formed in 12th weeks.the expression of MLCK mRNA was increased and peaked in the 6th to 9th weeks and then reduced in 12th weeks.Also,the expression of miR-92a had a similar trends with mRNA expression of MLCK.2.In VSMCs:(1)miR-92a inhibitor reduced the proliferation and migration of VSMCs under the stimulus of PDGF-BB.(2)MLCK inhibitor(ML-7)suppressed the migration of VSMCs in response to PDGF-BB.(3)In VSMC,miR-92a inhibitor reduced the formation of filopodia and promoted KLF4 gene expression.In MLCK-/VSMC,by contrast,miR-92a mimics partially restored the formation of filopodia and inhibited KLF4 gene expression.(4)ML-7 reduced the expression of miR-92a in a dose-dependent manner.(5)Compared with GbaSM-4,the expression of miR-92a was lower in MLCK-/VSMC.3.In additon,ML-7 suppressed miR-92a expression in the thoracic aortas of high-fat diet mice.Conclusion: MLCK is involved in atherosclerotic vascular remodeling through regulating the proliferation and migration of VSMCs via miR-92a.