AMP‐activated protein kinase activation is associated with an inhibition of fibrotic properties of cardiac fibroblasts

Abstract

PurposeWe asked whether cardiac fibroblast (CF) function might be regulated by AMP‐activated protein kinase (AMPK). We also investigated cardiac fibrosis in AMPK knockout mice (KO) after myocardial infarction.MethodsCF were treated by Transforming growth factor‐beta‐1 (TGF‐beta‐1), serum or platelet derived growth factor (PDGF‐BB) to stimulate myodifferentiation, proliferation and migration respectively. AMPK was activated prior to the different treatments with thienopyridone derivative A‐769662. For in vivo studies, KO mice and their wild‐type (WT) littermate were submitted to a ligation of the coronary artery to mimic myocardial infarction. Gene expression in the left ventricule was measured by qRT‐PCR.ResultsA‐769662 compound dose‐dependently prevented TGF‐beta‐ 1‐induced myodifferentiation. In addition, it decreased by 50% proliferation and completely prevented PDGF‐induced migration of CF, without affecting their mortality. Studies in KO mice show that RNA expression for collagen I and III was significantly increased in the infarct area of KO mice compared to WT mice, after myocardial infarction.ConclusionOur data indicate that AMPK could be a negative regulator of CF function, and by this way decrease the fibrotic component of ventricular remodelling which takes place after myocardial infarction.