Role of NO-sensitive guanylyl cyclase in angiogenesis and arteriogenesis

Abstract

Background As the main receptor for nitric oxide (NO), NO-sensitive guanylyl cyclase (NO-GC) is involved in the regulation of different physiological processes such as the regulation of blood pressure. cGMP synthesis increases upon NO generation by the endothelial NO synthase (eNOS) and mediates vascular smooth muscle relaxation. NO synthesis can be stimulated by the vascular endothelial growth factor (VEGF) which is an important stimulator of angiogenesis. The interconnection between the VEGF and the NO/ cGMP pathways is still unclear. In this project, we investigated the role of NO/cGMP signaling in angiogenesis and arteriogenesis using NO-GC-deficient mice. To investigate VEGF-mediated angiogenesis, the aortic ring assay was employed. Endothelial sprouting was measured in aortic rings from global NO-GC knockout mice (GCKO) and WT animals (see Figure 1). We also used the oxygen-induced retinopathy model (OIR) to monitor vessel loss and regrowth in vivo dependent on the presence of NO-GC (see figure 2). To determine a