GRK2 as negative modulator of NO bioavailability: Implications for cardiovascular disease

Cell Signal. 2018 Jan:41:33-40. doi: 10.1016/j.cellsig.2017.01.014. Epub 2017 Jan 7.

Abstract

Nitric oxide (NO), initially identified as endothelium-derived relaxing factor (EDRF), is a gaso-transmitter with important regulatory roles in the cardiovascular, nervous and immune systems. In the former, this diatomic molecule and free radical gas controls vascular tone and cardiac mechanics, among others. In the cardiovascular system, it is now understood that β-adrenergic receptor (βAR) activation is a key modulator of NO generation. Therefore, it is not surprising that the up-regulation of G protein-coupled receptor kinases (GRKs), in particular GRK2, that restrains βAR activity contributes to impaired cardiovascular functions via alteration of NO bioavailability. This review, will explore the specific interrelation between βARs, GRK2 and NO in the cardiovascular system and their inter-relationship for the pathogenesis of the onset of disease. Last, we will update the readers on the current status of GRK2 inhibitors as a potential therapeutic strategy for heart failure with an emphasis on their ability of rescuing NO bioavailability.

Keywords: Cardiovascular system; G protein-coupled receptor kinase; Nitric oxide; β-adrenergic receptor.

Publication types

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

MeSH terms

  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism*
  • G-Protein-Coupled Receptor Kinase 2 / antagonists & inhibitors
  • G-Protein-Coupled Receptor Kinase 2 / metabolism*
  • Humans
  • Models, Animal
  • Nitric Oxide / metabolism*
  • Protein Kinase Inhibitors / therapeutic use
  • Receptors, Adrenergic, beta / metabolism
  • Up-Regulation

Substances

  • Protein Kinase Inhibitors
  • Receptors, Adrenergic, beta
  • Nitric Oxide
  • G-Protein-Coupled Receptor Kinase 2