Abstract 216: Cathepsin-L Contributes to Ventricular Repair and Function Following Infarction through Enhanced Angiogenesis and Bone Marrow Cell Mobilization
Introduction: Cathepsin L (CTSL) is a member of the lysozomal protease family that facilitates cell migration in response to stress. Cardiac repair/remodeling following myocardial infarction (MI) requires inflammatory cell mobilization, angiogenesis and myofibroblast accumulation. We sought to determine whether CTSL influences cardiac repair/remodeling following MI.
Methods: MI was created in wild type (WT) and CTSL−/− knockout (KO) mice by LAD ligation. At day 3, 7, 14 and 28 post-MI, we evaluated function, morphology and molecular endpoints of repair and remodeling,
Result: CTSL activity was significantly increased in WT mice at day 3 of infarct region after MI. At day 28 after MI, the CTSL KO mice exhibited significant cardiac dilatation and dysfunction when compared with WT mice. They shown the left ventricular (LV) end-systolic pressure (LVESP) significantly decreased (47%) , LV end-systolic volume (LVESV) increased significantly (391%) in CTSL KO mice compared with control, but a less significant decrease of LVESP (21.2%) and 241% increased in LVESV in CTSL WT mice. Stroke volume, positive dp/dt, negative dp/dt, and fraction factors were also considerable different. MCP-5 and IL-8 expression, as well as macrophage infiltration were less evident in CTSL KO mice than WT mice with MI. This was associated with a paucity of newly formed vessels in the CTSL KO mice, and decreased associated VEGF expression. Myofibroblasts appeared at day 3, became more prominent at day 7 and remained evident at the site of MI at day 28 in WT mice. However, fewer myofibroblasts were present at the infarcted heart in CTSL KO mice. This may associated lack of constracture resulting in cardiac dilatation and ventricular dysfunction in CTSL KO mice.
Conclusions: Cathepsin L contributes to cardiac repair post infarction with improved remodeling and enhanced function by stimulating inflammatory cell moblizastion, myofibroblast accumulation and angiogenesis. This may represent a novel favorable protective pathway in post MI cardiac repair.