Effect Of KLF15 On Isoproterenol-induced Cardiac Hypertrophy And Study Of Its Mechanism

ObjectiveIncreasing evidence indicate that the Kruppel-like factor 15(KLF15),a memberof Cys2/His2 zinc-finger DNA-binding proteins,attenuates pressure-induced cardiac hypertrophy.However,the role of KLF15 in β1-adrenergic receptor agonists-induced cardiac hypertrophy is largely unknown and the exact molecular mechanism is not fully elucidated.MethodWe established the model of cardiac hypertrophy of mice induced byβ1-adrenergic receptor agonist isoproterenol.The heart weight/body weight ratios were measured.The morphological changes of myocardial cells were observed by H-E staining.The myocardial interstitial cells were observed by Sirius red staining.The cross-sectional area of cardiomyocytes was determined on sections stained with WGA.The changes of KLF 15 expression were established by real-time PCR and Western Blotn.Secondly,the model of cardiac hypertrophy induced by isoproterenol was established by using KLF 15 transgenic mice.To investigate the role of KLF 15 in isoproterenol-induced cardiac hypertrophy,we repeated the above experiments.The expression of autophagy and apoptosis-related proteins and Akt/mTOR signaling pathway proteins were detected by Western Blot to investigate the mechanism of KLF15 regulating isoproterenol-induced cardiac hypertrophy.Results1.Isoproterenol can increase the heart weight/body weight ratios and cross-sectional area,causing myocardial cell morphological changes and myocardial interstitial fibrosis.2.KLF15 was noticeably down-regulated in hypertrophic mice heart at both protein and mRNA levels in cardiac hypertrophy mouse model.3.KLF15 overexpression can reduce the heart weight/body weight ratios and cross-sectional area after myocardial hypertrophy in mice,inhibit the morphological changes and repress hypertrophy of cardiomyocyte interstitial fibrosis4.KLF15 overexpression inhibits apoptosis and induces autophagy in ISO-induced cardiac hypertrophy via Akt/mTOR signaling.ConclusionTaken together,our findings imply that KLF15 possesses potential anti-hypertrophic and anti-fibrotic functions,possibly via regulation of cell death pathways and the inhibition of Akt/mTOR signaling pathway.