Anti-angiogenic isoform of vascular endothelial growth factor-A in cardiovascular and renal disease

Abstract

Accumulating evidence suggests that pathologic interactions between the heart and the kidney can contribute to the progressive dysfunction of both organs. Recently, there has been an increase in the prevalence of cardiovascular disease (CVD) and chronic kidney disease (CKD) due to increasing obesity rates. It has been reported that obesity causes various heart and renal disorders and appears to accelerate their progression. Vascular endothelial growth factor-A (VEGF-A) is a major regulator of angiogenesis and vessel permeability, and is associated with CVD and CKD. It is now recognized that alternative VEGF-A gene splicing generates VEGF-A isoforms that differ in their biological actions. Proximal splicing that includes an exon 8a sequence results in pro-angiogenic VEGF-A165a, whereas distal splicing inclusive of exon 8b yields the anti-angiogenic isoform of VEGF-A (VEGF-A165b). This review highlights several recent preclinical and clinical studies on the role of VEGF-A165b in CVD and CKD as a novel function of VEGF-A. This review also discusses potential therapeutic approaches of the use of VEGF-A in clinical settings as a potential circulating biomarker for CVD and CKD.