What question did this study set out to answer?

The research aims to explore how Angiotensin‐(1–7) mitigates cardiac hypertrophy caused by isoproterenol by affecting autophagy and apoptosis.

March 28, 2026Open Access

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

Key Result

Angiotensin-(1-7) attenuates isoproterenol-induced cardiac hypertrophy and ventricular dysfunction by suppressing excessive autophagy and apoptosis via synergistic MasR and AT2R signaling.

Key Points

The research aims to explore how Angiotensin‐(1–7) mitigates cardiac hypertrophy caused by isoproterenol by affecting autophagy and apoptosis.
Created ISO-induced hypertrophy models in mice for analysis.
Utilized echocardiography, histology, and hypertrophic markers to assess cardiac function.
Conducted cell experiments on H9c2 cardiomyocytes with various receptor antagonists.
Applied pharmacological blockade and co-immunoprecipitation to study receptor interactions.
Employed transmission electron microscopy and TUNEL to evaluate autophagy and apoptosis.
Ang‐(1–7) improved ventricular function and reduced myocardial enlargement in the ISO-treated mice.
Found that receptor antagonists A‐779 and PD123319 indicated a need for MasR and AT 2 R interaction for effect.
Confirmed Ang‐(1–7) inhibited excessive autophagy and apoptosis in cardiomyocytes.
Receptor crosstalk between MasR and AT 2 R was necessary for the protective effects against cardiac hypertrophy.

Structured PICO

Does Angiotensin-(1-7) alleviate isoproterenol-induced cardiac hypertrophy in preclinical models?

Population

Mice with isoproterenol (ISO)-induced cardiac hypertrophy and H9c2 cardiomyocytes exposed to ISO

Intervention

Angiotensin-(1-7)

Comparator

ISO alone or receptor antagonists (A-779, PD123319)

Outcome

Cardiac hypertrophy, ventricular dysfunction, autophagy, and apoptosissurrogate

Angiotensin-(1-7) protects against isoproterenol-induced cardiac hypertrophy by suppressing autophagy and apoptosis through coordinated MasR and AT2R signaling, suggesting a potential therapeutic target.

Main Result

Absolute Event Rate: 0% vs 0%

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.