{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:54:21Z","timestamp":1791431661046,"version":"4.3.3"},"reference-count":35,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Metabolic reprogramming is a pivotal mechanism in the pathogenesis of pathological cardiac hypertrophy. Leucine\u2010rich repeat\u2010containing G protein\u2010coupled receptor 6 (Lgr6) has emerged as a significant player in cardiovascular diseases. In this study, the potential of Lgr6 to counteract pressure overload (PO)\u2010induced cardiac hypertrophy is investigated, and the underlying mechanisms involved are elucidated. Transverse aortic constriction (TAC) is induced to establish an in vivo cardiac hypertrophy model. Adeno\u2010associated virus 9 and adenovirus vectors are utilized to knock down and overexpress Lgr6 in cardiomyocytes, respectively. The effects of Lgr6 and its downstream molecules are subsequently determined using RNA sequencing and chromatin immunoprecipitation. Significant downregulation of Lgr6 expression is observed in the heart after TAC and in cardiomyocytes treated with phenylephrine. Lgr6 deficiency accelerated and Lgr6 overexpression inhibits cardiac hypertrophy and dysfunction after TAC. Mechanistically, the in vivo and in vitro experiments suggest that Lgr6 regulates the expression of ubiquitin specific protease 4 (USP4)\u00a0and peroxisome proliferator\u2010activated receptor alpha (PPAR\u03b1) by activating the cGMP\/PKG\/CREB1 signalling pathway, thereby regulating cardiomyocyte metabolic reprogramming after PO. Targeting Lgr6 can be a potential therapeutic strategy to treat pathological cardiac hypertrophy.<\/jats:p>","DOI":"10.1002\/advs.202417597","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T04:20:28Z","timestamp":1744345228000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Leucine\u2010Rich Repeat\u2010Containing G Protein\u2010Coupled Receptor 6 Ameliorates Pressure Overload\u2010Induced Cardiac Hypertrophy by Regulating Cardiomyocyte Metabolic Reprogramming"],"prefix":"10.1002","volume":"12","author":[{"given":"Mengmeng","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan 430060 China"},{"name":"Cardiovascular Research Institute Wuhan University Wuhan 430060 China"},{"name":"Hubei Key Laboratory of Cardiology Wuhan 430060 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