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Updated: Feb 25, 2026

Transverse Aortic Constriction in Mice
08:25

Transverse Aortic Constriction in Mice

Published on: April 21, 2010

69.3K

G protein-coupled receptor kinase 2 promotes cardiac hypertrophy

Philipp Schlegel1,2, Julia Reinkober1, Eric Meinhardt1

  • 1Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany.

Plos One
|August 1, 2017
PubMed

Insights

Increased G-protein coupled receptor kinase 2 (GRK2) drives cardiac hypertrophy by activating the Akt-GSK3β-NFAT pathway. Inhibiting GRK2 or its downstream effectors mitigates this hypertrophic response in heart failure models.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Upregulation of G-protein coupled receptor kinase 2 (GRK2) is a key feature of cardiac stress and heart failure.
  • GRK2 inhibition has shown promise in improving cardiac function and reducing adverse remodeling in preclinical models.

Purpose of the Study:

  • To investigate the role of GRK2 in cardiac hypertrophy.
  • To elucidate the molecular mechanisms by which GRK2 influences cardiac hypertrophy.

Main Methods:

  • Utilized mouse models with transverse aortic constriction (TAC) to induce cardiac stress.
  • Employed conditional GRK2 knockout mice and in vitro neonatal rat ventricular cardiac myocytes.
  • Investigated signaling pathways involving Akt, GSK3β, NFAT, and PI3Kγ.

Main Results:

  • TAC increased GRK2 expression in mice.
  • GRK2 knockout attenuated cardiac hypertrophy and preserved ventricular geometry post-TAC.
  • GRK2 overexpression in myocytes enhanced Akt signaling, inhibited GSK3β, and promoted NFAT activation.
  • GRK2 interacted with PI3Kγ, and inhibiting either PI3Kγ or GRK2 blocked Akt activation and NFAT signaling, reducing hypertrophy.

Conclusions:

  • Enhanced GRK2 expression initiates cardiac hypertrophy.
  • The GRK2-PI3Kγ interaction mediates Akt phosphorylation, leading to GSK3β inactivation and subsequent NFAT activation.
  • Targeting the GRK2 pathway offers a potential therapeutic strategy for cardiac hypertrophy.

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