81 Development of adverse cardiac remodelling in experimental diabetes is regulated by endothelial NOX4 nadph oxidase

BackgroundThe characteristic structural and functional cardiac abnormalities which occur in diabetes, including fibrosis, inflammation and microvascular remodelling, and result in increased susceptibility to cardiovascular stress are largely mediated by reactive oxygen species (ROS) generation. In this study we aimed to investigate the specific contribution of endothelial Nox4 NADPH oxidase, a major source of cardiovascular ROS, to adverse cardiac remodelling in experimental diabetes.MethodsDiabetes was induced in gene-modified mice with endothelial-specific Nox4 overexpression (Tg) and wild-type (WT) littermate controls (10–12 weeks old; n=8–12 per group) by streptozotocin injection (STZ, 50 mg/kg i.p. for 5 consecutive days). After 6 months, analyses of cardiac function (echocardiography), glucose metabolism (blood glucose, HbA1c) and myocardial gene expression (qPCR) were performed.ResultsEndothelial Nox4 overexpression had no effect on blood glucose or HbA1c levels in control or diabetic Tg animals. Tg control mice demonstrated impaired basal diastolic function (E/A ratio: WT 1.6±0.09 vs Tg 1.4±0.08, p