Autophagy fine-tuning by angiotensin-(1-9) in cultured rat cardiomyocytes.

Background: The renin-angiotensin system (RAS) plays a pivotal role in regulating blood volume, systemic vascular resistance, and electrolyte balance, serving as a key component of cardiovascular health. Recent findings highlight the role of angiotensin II (Ang II) in inducing autophagy through angiotensin II receptor type 1 (AT1R). Autophagy, a process of self-degradation and turnover of cellular components, is a homeostatic response that eliminates superfluous materials. Abnormal autophagy promotes cardiomyocyte loss and is critical in hypertrophy and heart failure progression. The RAS's non-canonical axis, which includes the angiotensin 1-9 peptide [Ang-(1-9)], has an anti-hypertrophic effect in cardiomyocytes via an unknown mechanism Methods: We Results: Our findings show that CQ leads to a reduction in autophagy markers, such as microtubule-associated protein 1 light chain 3-II (LC3-II) and total LC3, suggesting Ang-(1-9)'s regulatory role in basal autophagy levels. Furthermore, Ang-(1-9) opposes Ang-II-induced autophagy and induces the phosphorylation of the S234 residue of Beclin-1 (BCN1) via an angiotensin II receptor type 2 (AT2R)/Akt-dependent pathway. Conclusions: This reduction of Ang-II-induced autophagy by Ang-(1-9) unveils a novel aspect of its action, potentially contributing to its cardioprotective effects.