Study On The Mechanism Of Myocardial Myosin Light Chain Kinase (cMLCK) Involved In Regulating Myocardial Contractility During Aging

Objective: To investigate the regulatory mechanisms of cardiac myosin light chain kinase(c MLCK)and corresponding pathway in systolic ability of the aging heart,also to reveal the correlation of cardiomyosin systolic ability and c MLCK expression and activity.Method: Wistar rats(n=23)were divided into two groups and fed to four and thirty months separately to do tests including echocardiography,western blotting,immumohistochemical staining and nucleic acid assay.Neonatal rat primary cardiomyocytes were cultured as four different groups.Aging group and aging stress group were treated with DOX,following by removing serum and oxygen from stress group and aging stress group,as a group without any stimuli setting as control.Western blotting was done after experiment.Result: The Aging group(30 month old)had a higher left ventricular end-systolic dimension(LVEDs),left ventricular enddiastolic dimension(LVEDd),left ventricular posterior wall end systole(LV PWs)and left ventricular mass(LV mass)value than adult group had(4 month old)(all p<0.01).In addition,lower left ventricular ejection fraction(EF)and fractional shortening(FS)value(all p<0.01)presented in the aging group.Immunohistochemical Masson staining figure showed that fibrosis of aging heart obviously increased(p<0.01).The aging group of primary cardiomyocytes gave a positive result on increasing apoptosis and hypotrophy.As the ischemia happened,cardiomyocyte present a further apoptosis and hypotrophy in aging stress group but not in stress group.Western blotting result gave a decreasing expression of MLCK protein and down regulating of phosphorylated MLC2(p-MLC)in aging group.Interestingly,the expression of MLC2 stayed constant.After ischemia,both aging group and adult group presented a higher c MLCK and p-MLC2 expression(all p<0.05)as well as a lower end systolic pressure(ESP)and±dp/dt in both groups,meanwhile,overall aging group was lower than adult group(all p<0.01).Conclusion: Descending Expression and activity level of MLCK is relative to weaker cardiomyocin systolic ability in aging.The results prove that MLCK potentially can be a biomarker of heart aging progressing.