Tanshinol Borneol Ester Improves Pressure Overload-Induced Cardiac Hypertrophy Through Mitigating Autophagy

Abstract

Autophagy plays an important role in pressure overload-induced cardiac hypertrophy. Tanshinol borneol ester (DBZ), which is a combination of Dan Shen abstract and borneol, has been proved to be effective in attenuating various cardiovascular diseases. However, whether the effect of DBZ in attenuating cardiac hypertrophy is through regulation of autophagy is unknown. In this study, we investigated the effect of DBZ both in vitro and in vivo. Neonatal rat ventricular myocytes (NRCMs) were cultured to test the effect of DBZ in vitro, and transverse aortic coarctation (TAC) was performed in rats for in vivo study. Results demonstrated that DBZ reduced the size of heart, genes and proteins expression of hypertrophic markers, ROS generation, cellular stress, remodeling and ameliorated the function of left ventricular. Moreover, autophagy was significantly decreased, indicating that DBZ may improve cardiac hypertrophy by inhibiting autophagy. Finally, our results showed that DBZ regulates autophagy via mTOR/p70S6K and ERK1/2 rather than the p38 pathway. In conclusion, these results suggest that DBZ can attenuate cardiac hypertrophy through inhibiting autophagy via mTOR/p70S6K and ERK1/2 pathway. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (81873493 to D.S.), Science and technology innovation personnel of the Education Department of Henan Province (19HASTIT002 to D.S.), Science and Technology Leading Talents of Health Commission of Henan Province (51282 project, 100 to D.S.) 5451 Project of Henan Provincial Commission of Health and Family Planning (2015002 to D.S.). Additional support from the University-College Joint Cultivation Fund of Zheng Zhou University (2016-BSTDJJ-19), Henan Province’s Key Laboratory of Cardiac Injury and Repair. Declaration of Interests: All authors have no competing interests to declare, financial or otherwise. Ethics Approval Statement: All experimental protocols were approved by the Animal Research Center of Zheng Zhou University and conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 8523, revised 1996).