Abstract
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 (H2S) 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 H2S 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 H2S. Our findings showed that H2S could protect against cardiac hypertrophy by attenuating oxidative stress. The antioxidant roles of H2S 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, H2S may exert antioxidant effect on cardiac hypertrophy via PI3K/Akt-dependent activation of Nrf2 pathway.
Highlights
Cardiac hypertrophy, which is characterized by myocardial fibrosis, capillary rarefaction, inflammatory reaction, and cellular dysfunction, results in maladaptive ventricular remodeling and heart failure
Cardiac hypertrophy is a critical component of phenotype in the failing heart
Our results showed that PI3K siRNA-transfected cells exposed to Angiotensin II (Ang-II) and NaHS exhibited reduced expression of phosphorylated Akt and nuclear NF-E2-related factor 2 (Nrf2) and increased production of ROS compared with cells not transfected with PI3K siRNA (Figure 7A-7D)
Summary
Cardiac hypertrophy, which is characterized by myocardial fibrosis, capillary rarefaction, inflammatory reaction, and cellular dysfunction, results in maladaptive ventricular remodeling and heart failure. The mechanical stress and neurohumoral stimulation are primary triggering events of myocardial hypertrophy. Ventricular function is initially maintained by cardiac hypertrophy induced by pressure overload, and this is known as the adaptive phase. Hydrogen sulphide (H2S) has been recognized as a new gaseous signaling molecule aside from nitric oxide and carbon monoxide. It has multiple physiological and pharmacological properties such as cardioprotection, vasorelaxation, antioxidant and antiinflammatory effects [4]. We generated a mouse model of transverse aortic constriction (TAC) to investigate whether H2S has protective effect against cardiac hypertrophy
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