Downregulated endogenous sulfur dioxide/aspartate aminotransferase pathway is involved in angiotensin II-stimulated cardiomyocyte autophagy and myocardial hypertrophy in mice

Abstract Background The study was designed to investigate if endogenous sulfur dioxide (SO 2 ) was involved in cardiomyocyte autophagy and myocardial hypertrophy stimulated by angiotensin II (Ang II). Methods Thirty-two C57 mice were randomly divided into control, SO 2 , Ang II and Ang II+SO 2 groups. Human myocardial cell line H9c2 was divided into four groups including control, SO 2 , Ang II and Ang II+SO 2 groups. Blood pressure and myocardial hypertrophy of the mice were measured two weeks after Ang II administration. LC3 II/I ratio, and Beclin1, Atg4B and p62 expressions were determined both in vivo and in vitro . Autophagosome was observed in H9c2 cells with confocal microscope. Endogenous SO 2 generation and aspartate aminotransferase (AAT) expression were measured. Results In animal studies, hypertension and myocardial hypertrophy developed two weeks after Ang II administration. LC3 II/I ratio and Beclin1 and Atg4B expressions were markedly elevated ( P all P in vivo and in vitro . Compared with control group, endogenous SO 2 levels, AAT activity and AAT2 expression were obviously down-regulated ( P all 2 donor significantly reduced Ang II-induced myocardial hypertrophy in mice. LC3 II/I ratio and Beclin1 and Atg4B expressions were down-regulated ( P all P 2 both in vivo and in vitro . Conclusion Down-regulated endogenous SO 2 /AAT2 pathway might be involved in the pathogenesis of myocardial hypertrophy. SO 2 prevented Ang II -induced myocardial hypertrophy accompanied by down-regulating cardiomyocyte autophagy.