49 / 2021-07-30 21:18:27

A Novel peptide, ATH-1, regulates CaMKII to alleviate cardiac hypertrophy by inhibiting oxidative stress

Cardiac hypertrophy; ATH-1; ROS; CaMKII; ERK1/2

Pathological myocardial hypertrophy is the main cause of sudden death in patients with heart disease, exploring the pathogenesis of myocardial hypertrophy and develop new drugs is of great significance. We previously designed a new peptide, Athycaltide-1 (ATH-1), which is similar to a part of CaV1.2 channel protein and verified its effect in myocardial hypertrophy caused by isoproterenol. In this study, we observed the effect of ATH-1 on Ang II-induced myocardial hypertrophy and explored whether ATH-1 can inhibit CaMKII activation by inhibiting oxidative stress Myocardial hypertrophy models were in vivo with mice and in vitro with H9C2 cells. The experiments found that compared with the myocardial hypertrophy group, the heart-lung body weight ratio of the mice in the ATH-1 treatment group was significantly reduced. ATH-1 also reduced left ventricular posterior wall end systolic thickness (LVPWs), left ventricular posterior wall end diastolic thickness (LVPWd), ventricular septal end systolic thickness (IVSs) and ventricular septal end diastolic thickness (IVSd). ATH-1 significantly increased the the total antioxidant capacity in myocardial hypertrophic tissue and myocardial cells. In vivo and in vitro experiments have found that ATH-1 can inhibit the expression of Nox2, HDAC, p-HDAC and MEF2C, and reduce the expression of CaMKII, ox-CaMKII, p-CaMKII and p-ERK1/2. In conclusion, ATH-1 may alleviate cardiac hypertrophy by inhibiting oxidative stress through inhibiting CaMKII oxidation and phosphorylation, as well as ERK signaling pathways.