Ang? Facilitates MMP9-mediated MLCK Degradation In Pressure Overload-induced Cardiac Hypertrophy

Objective:Angiotensin ? has been shown to promote cardiac remolding in the process of hypertrophy.Myosin light chain kinase,a special kinase for phosphorylation of myosin light chian 2,plays an important role in regulating cardiac muscle contraction and hypertrophy.Several matrix metalloproteinases(MMPs),especially MMP-9,have been reported to play an important role in the course of cardiac disease,which is related to regulate expression of proteins and degradation of kinases.However,whether angiotensin ? could facilitate cardiac hypertrophy through altering the expression of myosin light chain kinase and MMP9 plays a part in MLCK degradation in cardiac remolding remains unclear yet.This study aimed to investigate whether angiotensin ? aggravates cardiac hypertrophy via altering myosin light chain kinase protien and the underlying molecular mechanisms.Methods:Cardiac hypertrophy was induced by abdominal aortic constrictio in rats,then evaluated via histological and biochemical measurements and echocardiography.Captopril was used for inhibition of angiotensin ?.Neonatal rat cardiomyocytes were stimulated with angiotensin ? to induce hypertrophy,and treated with matrix metalloproteinase-9 inhibitor.Myocyte hypertrophy was evaluated through Immunofluorescence and qRT-PCR.The expression levels of matrix metalloproteinase-9,myosin light chain kinase,myosin light chain 2,phospho-myosin light chain 2,myosin phosphatase 2 and calmodulin were measured using Western blotting.Results:Captopril improved cardiac function and remolding and increased levels of myosin light chain kinase and phospho-myosin light chain 2,additionally,reduced expression of matrix metalloproteinase-9 in pressure overload-induced cardiac hypertrophy.Moreover,matrix metalloproteinase-9 inhibitor alleviated myocyte hypertrophy and upregulated levels of myosin light chain kinase and phospho-myosin light chain 2 in angiotensin ?-induced cardiomyocyte hypertrophy.Conclusion:Our results suggest that angiotensin ? involves the degradation of myosin light chain kinase in pressure overload-induced cardiac hypertrophy,and this process was mediated by matrix metalloproteinase-9.