ALK1 Deficiency Impairs the Wound-Healing Process and Increases Mortality in Murine Model of Myocardial Infarction

AbstractThe functional role of TGF β type I receptor, activin-like kinase (ALK)-1 in post-myocardial infarction (MI) cardiac remodeling is unknown. We hypothesize that reduced ALK1 activity reduces survival and promotes cardiac fibrosis after MI. MI was induced in wild-type (WT), and ALK+/ − mice by left coronary ligation. After 14 days ALK1+/ − mice had reduced survival with a higher rate of cardiac rupture compared to WT mice. ALK1+/ − left ventricles (LVs) had increased volumes at the end of systole and at the end of diastole. After MI ALK1+/ − LVs had increased profibrotic SMAD3 signaling, type 1 collagen, and fibrosis as well as increased levels of TGF β1 co-receptor, endoglin, VEGF, and ALK1 ligands BMP9 and BMP10. ALK1+/ − LVs had decreased levels of stromal-derived factor 1 α. These data identify the critical role of ALK1 in post-MI survival and cardiac remodeling and implicate ALK1 as a potential therapeutic target to improve survival after MI.Graphical abstract
Source: Journal of Cardiovascular Translational Research - Category: Cardiology Source Type: research