Cited by 305Receptor Mechanisms and SignalingCardiac electrophysiology and arrhythmiasCardiovascular, Neuropeptides, and Oxidative Stress Research

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G-Protein–Coupled Receptors in Heart Disease

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Wang, Jialu, Gareri, Clarice, Rockman, Howard A.·2018·Circulation Research

DOI 10.1161/circresaha.118.311403PMC PMC6205195

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Abstract

GPCRs (G-protein [guanine nucleotide-binding protein]–coupled receptors) play a central physiological role in the regulation of cardiac function in both health and disease and thus represent one of the largest class of surface receptors targeted by drugs. Several antagonists of GPCRs, such as βARs (β-adrenergic receptors) and Ang II (angiotensin II) receptors, are now considered standard of therapy for a wide range of cardiovascular disease, such as hypertension, coronary artery disease, and heart failure. Although the mechanism of action for GPCRs was thought to be largely worked out in the 80s and 90s, recent discoveries have brought to the fore new and previously unappreciated mechanisms for GPCR activation and subsequent downstream signaling. In this review, we focus on GPCRs most relevant to the cardiovascular system and discuss traditional components of GPCR signaling and highlight evolving concepts in the field, such as ligand bias, β-arrestin–mediated signaling, and conformational heterogeneity.

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Authors: Wang, J., Gareri, C., & Rockman, H. A.
Affiliations: From the Department of Medicine (J.W., C.G., H.A.R.)
Duke University (US)
ORCID: Wang, Jialu
Gareri, Clarice
Rockman, Howard A.
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2018-08-31
Volume: 123
Issue: 6
Pages: 716-735
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/circresaha.118.311403
PMC: PMC6205195
OpenAlex: W2889986213
Cited by: 303
References: 259
Citations by year: 2026: 28 · 2025: 32 · 2024: 57 · 2023: 49 · 2022: 47 · 2021: 45 · 2020: 31 · 2019: 14
FWCI: 2.21
Type: journal article
Language: en
Update notices: correction (2018-10-25)
Open access: bronze
doi.org
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (P01HL075443, R01HL056687)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
Keywords: G protein-coupled receptors, heart disease, cardiac function, beta-adrenergic receptors, angiotensin II receptor, G protein-coupled receptor signaling, ligand bias, β-arrestin signaling, conformational heterogeneity, heart failure, hypertension, coronary artery disease, cardiovascular drug targets
MeSH terms: Animals, Cardiovascular Agents, Fibroblasts, Heart Failure, Heart Ventricles, Humans, Signal Transduction, Ventricular Function, Ventricular Remodeling, Myocytes, Cardiac, Myocytes, Smooth Muscle, Endothelial Cells, Receptors, G-Protein-Coupled

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