Atherosclerosis(AS)is an important pathological basis of cardiovascular events,and damage caused by AS is an important factor causing cardiovascular disease and death.In recent years,the study of the pathogenesis of atherosclerosis has been a hotspot in the field of cardiovascular disease.Pathogenesis of atherosclerosis is characterized by abnormal vascular smooth muscle cell(VSMC)proliferation,migration and inflammation.Myosin light chain kinase(MLCK)is the key enzyme that regulates smooth muscle contraction and plays a pivotal role during VSMC proliferation and migration.However,MLCK underlying role and mechanism in abnormal VSMC proliferation and migration remain unclear.In this study,we investigated MLCKs role and underlying mechanism in VSMC proliferation and migration using MLCK deficient guinea pig brain basilar artery smooth muscle cells(MLCK-/Gba)and parent cells treated with 20 ng/ml interleukin-8(IL-8)or vehicle.Results: 1.MLCK inhibited IL-8-induced VSMC proliferation and migration.2.MLCK deficiency decreased IL-8-induced cell cycle progression,decreased mRNA expression of cyclin D1,proliferating cell nuclear antigen(PCNA),myocyte enhancer factor 2A(Mef2A),decreased matrix metalloproteinase-2(MMP-2)expression and activity,and increased α-smooth muscle actin(α-SMA)expression levels.3.Phosphorylation of extracellular regulated kinase(ERK)was required for IL-8-regulated MMP-2 protein levels and activity as well as α-SMA protein levels in VSMCs.4.MLCK deficiency abrogated IL-8-induced phosphorylation of ERK in VSMCs.5.MLCK deficiency reversed the effect of U0126 on IL-8 induced increases in VSMC proliferation and migration.Conclusions: MLCK is required for IL-8-induced proliferation and migration via regulating cell cycle progression and expression of cyclin D1,PCNA,Mef2A,MMP-2 and α-SMA,as well as ERK phosphorylation.