Annexin A5 knockdown inhibits cardiomyocyte apoptosis and alleviates cardiac hypertrophy via activating the PI3K/AKT/Bcl-2 signaling pathway.

Annexin A5 (ANXA5) is a small calcium-dependent protein that binds specifically to negatively charged phosphatidylserine as a marker of apoptosis. Previous studies have shown that ANXA5 expression is elevated in hypertensive patients and is closely related to left ventricular systolic function in hypertensive patients, but its specific mechanism of action has not been clarified. GEO database analysis showed that ANXA5 expression was significantly upregulated in hypertensive myocardial hypertrophy. The expression of ANXA5 protein and mRNA was overexpressed, and knockdown of ANXA5 can effectively attenuate cardiomyocyte apoptosis and inflammatory response, ameliorate myocardial hypertrophy and cardiac dysfunction in ALD-induced hypertrophic cardiomyocytes and in SHR hypertrophic hearts. Mechanistically, ANXA5 has synergistic effect with intracellular calciumion level. In the meantime, ANXA5 knockdown inhibited cell apoptosis along with a decrease of Bax/Bcl-2 ratio, and induction of PI3K/AKT activation. It should be noted that LY290004 (PI3K/Akt signaling pathway inhibitor) can weaken the inhibitory effect of knockdown ANXA5 on cardiomyocyte apoptosis and myocardial protection. Therefore, ANXA5 knockdown improves hypertensive myocardial hypertrophy and cardiac function by inhibiting apoptosis and inflammatory response and activating PI3K/AKT/Bcl-2 pathway, ANXA5 may be a potential therapeutic direction for the treatment of hypertensive myocardial hypertrophy.