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Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 6 Ameliorates Pressure Overload-Induced Cardiac Hypertrophy

Mengmeng Zhao1,2,3, Jianfang Liu1,2,3, Shanshan Peng1,2,3

  • 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 11, 2025
PubMed

Insights

Leucine-rich repeat-containing G protein-coupled receptor 6 (Lgr6) counteracts pathological cardiac hypertrophy by regulating cardiomyocyte metabolism. Targeting Lgr6 offers a potential therapeutic strategy for heart disease.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Metabolic Regulation

Background:

  • Pathological cardiac hypertrophy involves significant metabolic reprogramming.
  • Leucine-rich repeat-containing G protein-coupled receptor 6 (Lgr6) is implicated in cardiovascular diseases.

Purpose of the Study:

  • To investigate the role of Lgr6 in counteracting pressure overload-induced cardiac hypertrophy.
  • To elucidate the underlying molecular mechanisms of Lgr6 action.

Main Methods:

  • Established a cardiac hypertrophy model using transverse aortic constriction (TAC) in vivo.
  • Utilized viral vectors for Lgr6 knockdown and overexpression in cardiomyocytes.
  • Employed RNA sequencing and chromatin immunoprecipitation to analyze molecular effects.

Main Results:

  • Lgr6 expression was downregulated in response to TAC and phenylephrine.
  • Lgr6 deficiency exacerbated TAC-induced cardiac hypertrophy and dysfunction.
  • Lgr6 overexpression inhibited cardiac hypertrophy and dysfunction post-TAC.

Conclusions:

  • Lgr6 plays a protective role against cardiac hypertrophy.
  • Lgr6 modulates ubiquitin specific protease 4 (USP4) and peroxisome proliferator-activated receptor alpha (PPARα) expression via the cGMP/PKG/CREB1 pathway.
  • Targeting Lgr6 presents a potential therapeutic avenue for pathological cardiac hypertrophy.

Keywords:
Lgr6PPARαUSP4cardiac hypertrophymetabolic reprogramming

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