What is the clinical evidence from this study?

Study design: Other. Population: Cardiac fibrosis. Intervention: Angiotensin-(1-7) and ACE2 over-expression vs. Control, LPS, Sham, AF-Control, AF-EGFP. Primary outcome: Cardiac fibrosis and fibroblast proliferation (p=<0.05).

What question did this study set out to answer?

The research aims to explore how Angiotensin-(1-7) impacts cardiac fibrosis through Rac1 and Rad GTPase regulation.

April 12, 2026

ACE2 Mediated Cardiac Fibrosis Alleviation Through Angiotensin‐(1‐7)/Mas Axis Regulation of the Renin‐Angiotensin System/Rac Signaling Pathway

Q: What are the key findings of this study?

ACE2 over-expression and Ang-(1-7) application alleviated cardiac fibrosis and inhibited fibroblast proliferation by modulating the Ang(1-7)/Mas signaling pathway (p < 0.05).

Q: What does this research mean for the field?

ACE2 over-expression and Ang-(1-7) application alleviate cardiac fibrosis and inhibit fibroblast proliferation by modulating the Ang(1-7)/Mas signaling pathway. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

The research aims to explore how Angiotensin-(1-7) impacts cardiac fibrosis through Rac1 and Rad GTPase regulation.

Key Result

ACE2 over-expression and Ang-(1-7) application alleviated cardiac fibrosis and inhibited fibroblast proliferation by modulating the Ang(1-7)/Mas signaling pathway (p < 0.05).

Key Points

The research aims to explore how Angiotensin-(1-7) impacts cardiac fibrosis through Rac1 and Rad GTPase regulation.
Isolated cardiac fibroblasts from Sprague-Dawley rats and treated with Ang-(1-7) and LPS.
Performed histopathological evaluations and immunoperoxidase staining to assess fibrosis and protein expression.
Conducted ELISA to measure Ang II and Ang-(1-7) levels in canine atrial tissue.
Used western blot analysis to detect protein expression related to fibrosis and signaling pathways.
LPS increased fibroblast proliferation, which Ang-(1-7) inhibited (p < 0.05).
In LPS-induced CFs, protein levels of iNOS, COX2, and α-SMA were significantly up-regulated and reversed by Ang-(1-7).
ACE2 over-expression in canine models increased Ang-(1-7) levels and reduced Ang II and AT1R expressions (p < 0.05).
In the AF-ACE2 group, Rac1 was down-regulated and Rad GTPase up-regulated, along with decreased fibrosis markers.

Structured PICO

Does Angiotensin-(1-7) and ACE2 over-expression alleviate cardiac fibrosis in rat cardiac fibroblasts and canine atrial rapid pacing models?

Population

Rat cardiac fibroblasts (CFs) from 1-3 day-old Sprague-Dawley rats and mongrel dogs with atrial rapid pacing (AF) models

Intervention

Angiotensin-(1-7) application (in vitro) and ACE2 over-expression (in vivo)

Comparator

Control and LPS groups (in vitro); Sham, AF-Control, and AF-EGFP groups (in vivo)

Outcome

Cardiac fibrosis extent, cell proliferation, and expression of Rac1, Rad GTPase, and RAS componentssurrogate

ACE2 over-expression and Ang-(1-7) alleviate cardiac fibrosis through the Ang(1-7)/Mas signaling pathway and regulation of Rac1/Rad GTPase in preclinical models of atrial fibrillation.

Main Result

p-value: p=<0.05

Abstract

This study aimed at investigating whether Angiotensin-(1-7) Ang-(1-7) could alleviate cardiac fibrosis by modulating the expression of Rac1 and Rad GTPase and evaluating the specific mechanism in rat cardiac fibroblasts (CFs) and in canine atrial rapid pacing models. Fresh CFs were isolated from ventricles of 1 ~ 3 day-old Sprague-Dawley rats, and were randomly divided into control group, LPS group, Ang-(1-7) group and LPS+Ang-(1-7) group. CCK8 was used to detect cell proliferation. qRT-PCR was to detect the mRNA expression of ACE2. Mongrel dogs were randomized into four groups: Sham-operated (Sham), AF-Control, AF-EGFP and AF-ACE2 groups. Immunoperoxidase staining was used to test Rac1 and Gem expression. Collagen fibers in heart were stained a red color and extent of cardiac fibrosis was evaluated. Histopathology was to observe actin,α-smooth. Enzyme-Linked Immunosorbent Assay was to detect Ang II and Ang-(1-7) expression in canine atrial tissue. And western blot analysis was to detect the protein expression of iNOS, COX2, α-SMA, Rac1, ACE, and AT1R in cells and tissues. Cellular experiments showed LPS promoted proliferation of fibroblasts, which could be inhibited by Ang-(1-7) (p < 0.05). Compared with control group, LPS-induced CFs showed a significant increase in protein expression of iNOS, COX2, and α-SMA, which promoted cell proliferation. However, the application of Ang-(1-7) reversed these effects and suppressed the ACE/AT1R signaling pathway in LPS-induced CFs. In animal experiments, ACE2 over-expression would up-regulate atrial Ang-(1-7) and AT2R and reduce atrial angiotensin II (Ang II) and AT1R expressions (p < 0.05). In AF-ACE2 group, Rac1 was down-regulated and Rad GTPase was up-regulated, in comparison with AF-Control and AF-EGFP groups, associated with reductions of CTGF, fibrosis-related factors α-SMA and N-cadherin. ACE2 was found to alleviate cardiac fibrosis through the Ang(1-7)/Mas signaling pathway in animal experiments.

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