Work

Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

Year: 2026

Type: article

Abstract: ABSTRACT Aim The aim of this study is to determine whether Angiotensin‐(1–7) [Ang‐(1–7)] alleviates isoproterenol (ISO)–induced cardiac hypertrophy by suppressing excessive autophagy and apoptosis through coordinated Mas receptor (MasR) and angiotensin II type‐2 receptor (AT 2 R) signaling, and to elucidate the underlying mechanisms. Methods ISO‐induced hypertrophy was established in mice and assessed by echocardiography, histology, and hypertrophic markers. H9c2 cardiomyocytes were exposed to ISO and treated separately with A‐779 (MasR antagonist), PD123319 (AT 2 R antagonist), and a combination of both receptor antagonists. Receptor interplay was examined using pharmacological blockade and co‐immunoprecipitation. Autophagy and apoptosis were evaluated by transmission electron microscopy and TUNEL. Results Ang‐(1–7) attenuated ventricular dysfunction, myocardial enlargement, and upregulation of hypertrophic markers in mice with ISO‐induced hypertrophy. Pharmacological inhibition with A‐779 and PD123319 revealed that Ang‐(1–7) actions require reciprocal regulation between MasR and AT 2 R. Both receptors synergistically contributed to the anti‐apoptotic effect, while the anti‐autophagic response was mediated predominantly by MasR. Transmission electron microscopy and TUNEL staining confirmed that Ang‐(1–7) treatment alleviated excessive autophagy and apoptosis in cardiomyocytes. Furthermore, experiments with dual receptor antagonists and co‐immunoprecipitation showed an interaction between MasR and AT 2 R, supporting their coordinated signaling role in cardiac protection. Conclusion Ang‐(1–7) ameliorates ISO‐induced cardiac hypertrophy by suppressing excessive autophagy and apoptosis via synergistic MasR–AT 2 R signaling. Receptor crosstalk may represent a therapeutic entry point for pathological hypertrophy.

Source: Acta Physiologica

DOI: 10.1111/apha.70200