Regulation of retinal angiogenesis by endothelial nitric oxide synthase signaling pathway

Abstract

Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and vascular smooth muscle cell coverage to blood vessels were attenuated in mice lacking eNOS. Taken together, we suggest that the endothelial cell function and blood vessel maturation are regulated by eNOS during retinal angiogenesis.

Angiogenesis in the atherosclerotic plaque

“…In addition to its vasodilator effect and its role in the regulation of arterial blood pressure, NO synthesized by endothelial cells could be involved in vascular remodeling and angiogenesis [179] , [180] . eNOS regulates endothelial cell proliferation and sprouting, and pericytes recruitement for blood vessel stabilization [181] . NO-induced vasodilatation and a cross talk between eNOS and the VEGF pathway may explain the angiogenic potential of NO [182] .…”

mTORc1 activity is necessary and sufficient for phosphorylation of eNOSS1177

“…eNOS, the predominant isoform expressed within the vasculature, is responsible for most of the NO production contributing to vascular tone, angiogenesis, and vascular permeability (Nathan and Xie 1994). Its importance in regulating vascular function is underscored by the array of phenotypes exhibited in eNOS-knockout mice, for example hypertension (Huang et al 1995), increased vascular smooth muscle cell proliferation in response to injury (Moroi et al 1998), increased leukocyte-endothelial interactions (Lefer et al 1999), hypercoagulability (Freedman et al 1999), and exacerbated atherosclerosis within diet-induced models (Chen et al 2001;Kuhlencordt et al 2001), as well as an essential role in retinal angiogenesis (Ha et al 2016).…”

Platelet‐derived growth factor‐AA is a substantial factor in the ability of adipose‐derived stem cells and endothelial progenitor cells to enhance wound healing

“…Numerous studies have shown that eNOS may regulate antiproliferative and antiapoptotic effects and maintain the proper basal vasodilator tone of blood vessels during tissue repair (38)(39)(40)(41)(42). Previous studies have shown a severe impairment of angiogenesis in eNOS-deficient mice and that blood vessel maturation and endothelial cell function are regulated by eNOS during angiogenesis (38,40). In the present study, we have demonstrated that the PI3K/AKT/ eNOS pathway is a downstream effector of PDGF-AA and provided direct evidence that PI3K/AKT/eNOS expression is downregulated by the loss of PDGF-AA function in ASCs.…”