Protective effect of hydrogen sulphide against myocardial hypertrophy in mice

Cardiac hypertrophy is a critical component of phenotype in the failing heart. Recently, increasing evidence has demonstrated that oxidative stress plays an important role in the pathogenesis of myocardial hypertrophy. In the present study, we generated a mouse model of transverse aortic constriction (TAC) to investigate whether hydrogen sulfide (H(2)S) has protective effects against cardiac hypertrophy. Left ventricular structure was analyzed by two-dimensional echocardiography. Oxidative stress was evaluated by measuring malondialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen specie in the myocardium. Angiotensin II (Ang-II) was used to induce cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes pretreated with H(2)S donor sodium hydrosulfide prior to Ang-II exposure were used to determine the involvement of Nrf2 and PI3K/Akt pathway in the antioxidant effects of H(2)S. Our findings showed that H(2)S could protect against cardiac hypertrophy by attenuating oxidative stress. The antioxidant roles of H(2)S in myocardial hypertrophy probably depend on the activation of PI3K/Akt signaling, which consequently increases Nrf2 activity and HO-1 and GCLM expression. In summary, H(2)S may exert antioxidant effect on cardiac hypertrophy via PI3K/Akt-dependent activation of Nrf2 pathway.