Expression profile of total VEGF, VEGF splice variants and VEGF receptors in the myocardium and arterial vasculature of diabetic and non-diabetic patients with coronary artery disease

Background: Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and is implicated in the development of diabetic microvascular and macrovascular disease. Methods: The expression of total VEGF, VEGF splice variants (VEGF121, VEGF145, VEGF148, VEGF165, VEGF183 and VEGF189), VEGFR-1 and VEGFR-2, was investigated in biopsies from the right atrium and left internal mammary artery (LIMA) of 32 non-diabetic and 20 diabetic patients undergoing coronary artery bypass grafting. Results: Diabetes was independently negatively correlated to total VEGF mRNA expression in atrium. Total VEGF, VEGF121 and VEGF165 mRNA levels were upregulated in the LIMA of diabetics vs. non-diabetics. The expression of VEGF receptors in atrium and LIMA was similar between these groups. VEGF121 and VEGF165 were the major variants expressed, followed by VEGF189 and VEGF183, while VEGF148 and VEGF145 were detected in small amounts. The expression profile of VEGF splice variants displayed significant heterogeneity between the examined tissues. Conclusions: This is the first study to quantify VEGF splice variants expression in cardiac and vascular tissue. Our results could help elucidate the role of VEGF splice variants in diabetic complications.