Mechanism of over-expression of SEL1L in alleviating cardiac structural and functional damage caused by transverse aortic constriction in mice

  AIM  To investigate the effect of over-expression of suppressor/enhancer of Lin12-like (SEL1L) on cardiac structural and functional damage caused by transverse aortic constriction (TAC) and its underlying mechanism.

  METHODS  Myocardial hypertrophy model was established by TAC operation. Forty male C57BL/6 mice were randomly divided into 4 groups: Sham group, TAC group, TAC+AAV9-Ctrl group and TAC+AAV9-SEL1L group. Mice in TAC+AAV9-Ctrl group and TAC+AAV9-SEL1L group underwent TAC surgery 4 weeks after intramuscular spot injection of 10¹¹ units of AAV9-Ctrl and AAV9-SEL1L virus particles. Cardiac functions were detected, myocardial hypertrophy, myocardial fibrosis and myocardial apoptosis were determined, and myocardial endoplasmic reticulum stress and oxidative stress were observed.

  RESULTS  Compared with those in Sham group, mRNA and protein expressions of SEL1L in TAC group were significantly decreased, cardiac functions were significantly impaired, cardiomyocytes and heart were significantly enlarged, myocardial fibrosis was significantly aggravated, and cardiomyocyte apoptosis was significantly increased. Besides, the levels of endoplasmic reticulum stress and oxidative stress were significantly up-regulated in TAC group (all P<0.05). Compared with those in TAC group, mRNA and protein expressions of SEL1L in TAC+AAV9-SEL1L group were significantly increased, cardiac functions were significantly improved, cardiomyocytes and cardiac hypertrophy were significantly alleviated, myocardial fibrosis was significantly mitigated, and cardiomyocyte apoptosis was significantly inhibited. Additionally, the levels of endoplasmic reticulum stress and oxidative stress were significantly down-regulated in TAC+AAV9-SEL1L group (all P<0.05). But the above indexes in TAC+AAV9-Ctrl group had no significant difference compared with those in TAC group.

  CONCLUSION  Over-expression of SEL1L reduces cardiac structural and functional damage caused by transverse aortic constriction in mice through inhibiting endoplasmic reticulum stress and oxidative stress.