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Studies have shown that transgenic mice with G\u03b1q receptor blockade exhibit reduced hypertrophy under induced pressure overload. GQ262, a novel G\u03b1q\/11 inhibitor, has demonstrated good biocompatibility and specific inhibitory effects on G\u03b1q\/11 compared to other inhibitors. However, its role in cardiac remodeling remains unclear. This study aims to explore the anti-cardiac remodeling effects and mechanisms of GQ262 both in vitro and in vivo, providing data and theoretical support for its potential use in treating cardiac remodeling diseases. Cardiac hypertrophy was induced in mice via transverse aortic constriction (TAC) for 4 weeks and in H9C2 cells through phenylephrine (PE) induction, confirmed with WGA and H&amp;E staining. We found that GQ262 improved cardiac function, inhibited the protein and mRNA expression of hypertrophy markers, and reduced the levels of apoptosis and fibrosis. Furthermore, GQ262 inhibited the Akt\/mTOR signaling pathway activation induced by TAC or PE, with its therapeutic effects disappearing upon the addition of the Akt inhibitor ARQ092. These findings reveal that GQ262 inhibits cardiomyocyte hypertrophy and apoptosis through the Akt\/mTOR signaling pathway, thereby reducing fibrosis levels and mitigating cardiac remodeling.<\/jats:p>","DOI":"10.3390\/ijms251910297","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T04:01:24Z","timestamp":1727236884000},"page":"10297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["GQ262 Attenuates Pathological Cardiac Remodeling by Downregulating the Akt\/mTOR Signaling Pathway"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0529-5368","authenticated-orcid":false,"given":"Haoyue","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China"},{"name":"State Key Laboratory of Vascular 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