Cathepsin K Inhibitor Inhibits Resistin-induced Cardiomyocytes Hypertrophy Through LKB1/AMPK Pathway

Objective:To explore the effect and mechanism of Odanacatib(ODN) on resistin-induced cardiomyocytes hypertrophy, and provide new theoretical basis for the prevention and treatment of myocardial hypertrophy and heart failure.Methods:H9c2 rat myocardial cells were cultured in DMEM containing 10% FBS, replacing new nutrient solution every 2 days. Cells needed to be subcultured when they grew to70%-80% of the area of the culture bottle bottom. Observed the cells under inverted microscope and chose those which grew well. Experiment was divided into three groups:the control group, the resistin group and the resistin + ODN group. Then the surface area size and the protein synthesis of the cells were detected. The expression of cardiomyocytes hypertrophy markers BNP and β-MHC were detected by RT-qPCR technology. Western blot was used to analyze the expression and phosphorylation of AMPK and LKB1.Results:Resistin could significantly increase H9c2 cardiomyocytes cells surface area,promote protein synthesis, upregulation embryonic genes BNP and β-MHC, inhibit the phosphorylation of AMPK and LKB1, and ODN could significantly reverse the above phenomenon.Conclusion:ODN can inhibit the H9c2 cardiomyocyte hypertrophy induced by resistin. The underly mechanism may be involving LKB1/AMPK pathway.