Hypoxia preconditioned mesenchymal stem cells prevent cardiac fibroblast activation and collagen production via leptin

Aims: Activation of cardiac fibroblasts into myofibroblasts constitutes a key step in cardiac remodeling after myocardial infarction (MI), due to interstitial fibrosis. Mesenchymal stem cells (MSCs) have been shown to improve post-MI remodeling an effect that is enhanced by hypoxia preconditioning (HPC). Leptin has been shown to promote cardiac fibrosis. The expression of leptin is significantly increased in MSCs after HPC, but it is unknown whether leptin contributes to MSC therapy or the fibrosis process. The objective of this study was to determine whether leptin secreted from MSCs modulates cardiac fibrosis.
Methods: Cardiac fibroblast (CF) activation was induced by hypoxia (0.5% O2). The effects of MSCs on fibroblast activation were analyzed by co-culturing MSCs with CFs and detecting the expression of a-SMA, SM22a, and collagen IaI in CFs by western blot, immunofluorescence and Sirius red staining. In vivo MSCs antifibrotic effects on left ventricular remodeling were investigated ...