087 Blockade of VEGF-B Improves Cardiac Function after Myocardial Infarction in Insulin-Resistant Mice

Abstract

Anti-vascular endothelial growth factor B (VEGF-B) strategies have recently been shown to reduce toxic lipid accumulation in heart and to improve cardiac glucose uptake in rodents. We now investigate whether anti-VEGF-B treatment improves heart function following acute myocardial ischaemia-reperfusion in the setting of type 2 diabetes where cardiac insulin responsiveness and glucose uptake are impaired. Insulin-resistant (High fat diet, HFD) mice were treated with anti-VEGF-B or control antibody (20 mg/kg, ip) twice weekly for 5 weeks including three weeks before and two weeks after surgically-induced myocardial infarction (MI). One hour post-reperfusion, cardiac glucose uptake was assessed by FDG-PET/CT and two weeks later left ventricular (LV) function was measured by echocardiography Two weeks post-myocardial infarction (MI) and in comparison with control, anti-VEGF-B treatment reduced infarct size by 29±6% (mean±SEM) and enhanced left ventricular systolic function as measured by a 19±4% increase in ejection fraction and a 38±6% increase in fractional shortening (p<0.05 for all). Anti-VEGF-B treatment also trended to limit post-ischemic left ventricular dilatation by reducing both end diastolic and end systolic volumes. This was aligned with the finding of lower heart mass after myocardial infarction after treatment with anti-VEGF-B antibody compared to control (p<0.05). However, anti-VEGF-B treatment did not significantly modulate cardiac glucose uptake of HFD mice one hour after myocardial infarction This study demonstrates that anti-VEGF-B therapy improves the left ventricular systolic function of insulin-resistant mice after myocardial infarction. The mechanisms underlying this effect remain to be determined.