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Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
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Targeting GPCRs to treat cardiac fibrosis

Hao Zhang1, Lu Ren1, Rabindra Vishwadev Shivnaraine2

  • 1Department of Medicine, Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University, Stanford, CA, United States.

Frontiers in Cardiovascular Medicine
|October 24, 2022
PubMed

Insights

Cardiac fibrosis, a key factor in heart failure, lacks targeted therapies. This review explores G protein-coupled receptors (GPCRs) as novel therapeutic targets to combat cardiac fibrosis and improve heart function.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Pharmacology

Background:

  • Cardiac fibrosis is a significant contributor to myocardial stiffness and heart failure progression across various conditions like ischemic heart failure, cardiomyopathies, diabetes, and aging.
  • Despite identified anti-fibrotic targets such as TGF-β, no FDA-approved drugs specifically address cardiac fibrosis, highlighting a critical unmet medical need.
  • G protein-coupled receptors (GPCRs), with their diverse and cell-specific expression, represent promising, yet largely untapped, therapeutic targets for cardiac fibrosis.

Purpose of the Study:

  • To review the emerging roles of specific G protein-coupled receptors (GPCRs) in the development of cardiac fibrosis.
  • To explore the downstream signaling pathways of these GPCRs that are critical in myofibroblast activation and fibrosis progression.
  • To discuss the challenges in developing anti-fibrotic therapies and propose strategies to overcome them.

Main Methods:

  • Literature review focusing on G protein-coupled receptors (GPCRs) implicated in cardiac fibrosis.
  • Analysis of GPCR expression on cardiac fibroblasts and their role in myofibroblast activation.
  • Examination of indirect crosstalk mechanisms through which GPCRs contribute to cardiac fibrosis.

Main Results:

  • Several GPCRs are identified as key players in cardiac fibroblast activation and myofibroblast differentiation.
  • Both direct and indirect mechanisms involving GPCRs significantly contribute to the fibrotic process in the heart.
  • Understanding GPCR signaling pathways offers new avenues for therapeutic intervention.

Conclusions:

  • G protein-coupled receptors (GPCRs) present a novel and promising class of targets for anti-fibrotic therapies in the heart.
  • Targeting specific GPCRs and their downstream pathways could lead to effective treatments for cardiac fibrosis, mitigating heart failure progression.
  • Addressing the challenges in drug development is crucial for realizing the therapeutic potential of GPCRs in cardiac fibrosis.
Keywords:
G proteinGPCRantifibrotic therapycardiac fibrosiscrosstalkfibroblast

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