Pharmacological and Activated Fibroblast Targeting of Gβγ-GRK2 After Myocardial Ischemia Attenuates Heart Failure Progression.

ABSTRACT:

Background

Cardiac fibroblasts are a critical cell population responsible for myocardial extracellular matrix homeostasis. Upon injury or pathological stimulation, these cells transform to an activated myofibroblast state and play a fundamental role in myocardial fibrosis and remodeling. Chronic sympathetic overstimulation, a hallmark of heart failure (HF), induces pathological signaling through G protein βγ (Gβγ) subunits and their interaction with G protein-coupled receptor kinase 2 (GRK2).

Objectives

This study investigated the hypothesis that Gβγ-GRK2 inhibition and/or ablation after myocardial injury would attenuate pathological myofibroblast activation and cardiac remodeling.

Methods

The therapeutic potential of small molecule Gβγ-GRK2 inhibition, alone or in co

SUBMITTER: Travers JG 

PROVIDER: S-EPMC5564231 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature