AMPKα1 deletion in myofibroblasts exacerbates post-myocardial infarction fibrosis by a connexin 43 mechanism

Bruxelles Woluwe

A study from IREC Cardiovascular Research Pole (Sandrine Horman, Cécile Dufeys), in collaboration with Cliniques Universitaires Saint-Luc and KU Leuven, published in Basic Research Cardiology, 2021

The study highlights the crucial role of AMPKα1 in controlling myofibroblast (MF) properties, scar formation, and LV remodelling after myocardial infarction (MI). Mice with MF-specific deletion of AMPKα1 develop a more tightly-packed collagen scar after MI with a hyperproliferative fibroblast response, and suffer from adverse LV remodelling and functional impairment in the first months after MI. Downregulation of Connexin 43 (Cx43) probably contributes to the pro-fibrotic response. Mechanistically, AMPKα1 mainly influences Cx43 expression by a transcriptional mechanism. In addition, a microRNA, miR-125b-5p, can play a fine-tuning role to silence Cx43 and serve as a positive regulator in the fibrotic remodelling process.

This work adds momentum to the emerging notion that dampening MF in a timely fashion, that does not interfere with its role in cardiac repair, may be a new therapeutic strategy in heart failure prevention. AMPKα1 — as a novel central regulator of cardiac fibroblast activity — might constitute a potential target for pharmacological anti-fibrotic applications.

The full article is available to download here below.

Publié le 25 février 2021