Arteriolar genesis and angiogenesis induced by endothelial nitric oxide synthase overexpression results in a mature vasculature

A V Benest, O A Stone, W H Millar, C J Glover, JB Uney, A H Baker, S J Harper, DO Bates

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

BACKGROUND: Generation of physiologically active vascular beds by delivery of combinations of growth factors offers promise for vascular gene therapy. METHODS AND RESULTS: In a mesenteric model of physiological angiogenesis, combining endothelial nitric oxide synthase (eNOS) (and hence NO production) with VEGF and angiopoietin-1 overexpression resulted in a more functional vascular phenotype than growth factor administration alone. eNOS gene delivery upregulated eNOS, VEGF, and Ang-1 to similar levels as gene transfer with VEGF or Ang-1. eNOS overexpression resulted in neovascularization to a similar extent as VEGF and Ang-1 combined, but not by sprouting angiogenesis. Whereas combining Ang-1 and VEGF increased both exchange vessels and conduit vessels, neither growth factor nor eNOS alone resulted in vessels with smooth muscle cell (SMC) coverage. In contrast, combining all three generated microvessels with SMCs (arteriolar genesis) and further increased functional vessels. Use of a vasodilator, prazosin, in combination with Ang1 and VEGF, but not alone, also generated SMC-positive vessels. CONCLUSIONS: Coexpression of eNOS, VEGF, and Ang-1 results in a more mature vascularization of connective tissue, and generates new arterioles as well as new capillaries, and provides a more physiological therapeutic approach than single growth factor administration, by combining hemodynamic forces with growth factors.
Translated title of the contributionArteriolar genesis and angiogenesis induced by endothelial nitric oxide synthase overexpression results in a mature vasculature
Original languageEnglish
Pages (from-to)1462 - 1468
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume8
DOIs
Publication statusPublished - Aug 2008

Fingerprint Dive into the research topics of 'Arteriolar genesis and angiogenesis induced by endothelial nitric oxide synthase overexpression results in a mature vasculature'. Together they form a unique fingerprint.

Cite this