Cardiac hypertrophy is an independent risk factor for heart failure. However, the underlying mechanisms of cardiac hypertrophy are still unclear. Nintedanib is a Food and Drug Administration (FDA) approved therapeutic agent for the treatment of progressive fibrosing lung diseases.

Material and methods:
In this study, we examined the effects of nintedanib on cardiac hypertrophy using an in vivo murine model with the transverse aortic constriction (TAC) operation and an in vitro cardiomyocytes model stimulated with Ang II.

Nintedanib has a protective effect on cardiac function in TAC mice with decreased heart rates, heart weight/body weight (HW/BW), and reduced plasma levels of creatine kinase-MB (CK-MB) and aspartate aminotransferase (AST). Wheat germ agglutinin (WGA) staining proved that the increased cardiomyocytes sizes in TAC mice were restored by nintedanib treatment. Nintedanib also reversed the decreased plasma levels of oxidative markers nuclear factor erythroid-2-related factor 2 (Nrf2), lipid peroxidation products thiobarbituric acid reactive substances (TBARS), and GSH, as well the increased homocysteine (Hcy) levels in TAC mice. In the in vitro cardiomyocytes model, cells were treated with nintedanib, followed by Ang II stimulation. Nintedanib improved Ang II induction-caused cell injury and oxidative stress in H9C2 cells, as shown by the decreased release of lactate dehydrogenase (LDH), and elevated mRNA levels of GPX1 and HO-1. Mechanistically, we prove that the protective effect of nintedanib is mediated by SIRT1.

In conclusion, this study demonstrates the protective effects of nintedanib on cardiac hypertrophy both in vivo and in vitro, which was attributed to its anti-oxidative activity through regulating SIRT1 expression.

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