G-Protein-Coupled Receptors in Heart Disease

Circ Res. 2018 Aug 31;123(6):716-735. doi: 10.1161/CIRCRESAHA.118.311403.


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.

Keywords: GPCR; arrestin; bias; coronary artery disease; heart failure; hypertension.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cardiovascular Agents / therapeutic use
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Heart Failure / drug therapy
  • Heart Failure / metabolism*
  • Heart Failure / pathology
  • Heart Failure / physiopathology
  • Heart Ventricles / drug effects
  • Heart Ventricles / metabolism*
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Humans
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Receptors, G-Protein-Coupled / drug effects
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction* / drug effects
  • Ventricular Function* / drug effects
  • Ventricular Remodeling


  • Cardiovascular Agents
  • Receptors, G-Protein-Coupled