Inhibition of matrix metalloproteinases improves left ventricular function in mice lacking osteopontin after myocardial infarction

摘要: Osteopontin (OPN) plays an important role in left ventricular (LV) remodeling after myocardial infarction (MI) by promoting collagen synthesis and accumulation. This study tested the hypothesis that MMP inhibition modulates post-MI LV mice lacking OPN. Wild-type (WT) OPN knockout (KO) were treated daily with inhibitor (PD166793, 30 mg/kg/day) starting 3 days post-MI. functional structural was measured 14 Infarct size similar WT KO groups or without inhibition. M-mode echocardiography showed greater increase end-diastolic (LVEDD) end-systolic diameters (LVESD) decrease percent fractional shortening (%FS) ejection fraction KO-MI versus WT-MI. decreased LVEDD LVESD, increased %FS both groups. Interestingly, effect more pronounced group WT-MI (P < 0.01). significantly dilation as Langendorff-perfusion analysis. improved developed pressures MI However, improvement higher 0.05). heart weight-to-body weight ratio, myocyte cross-sectional area, fibrosis septal wall thickness only KO-MI. Percent apoptotic myocytes non-infarct area not different between treatment Expression activity of MMP-2 MMP-9 reduced no on expression TIMP-2 TIMP-4 Thus, activation MMPs contributes to dysfunction