Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve

Murata, Takahisa (author): Yale University School of Medicine, New Haven, CT, USA

Escalante, Bruno (author): Centro de Investigación y de Estudios Avanzados del Instituto Politecnico Nacional, Mexico

Sessa, William C (author): Yale University School of Medicine, New Haven, CT, USA

(creator_code:org_t)

2005-07-25
2005
English.
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 102:31, s. 10999-11004

Related links:: https://europepmc.or...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

The genetic loss of endothelial-derived nitric oxide synthase (eNOS) in mice impairs vascular endothelial growth factor (VEGF) and ischemia-initiated blood flow recovery resulting in critical limb ischemia. This result may occur through impaired arteriogenesis, angiogenesis, or mobilization of stem and progenitor cells. Here, we show that after ischemic challenge, eNOS knockout mice [eNOS (-/-)] have defects in arteriogenesis and functional blood flow reserve after muscle stimulation and pericyte recruitment, but no impairment in endothelial progenitor cell recruitment. More importantly, the defects in blood flow recovery, clinical manifestations of ischemia, ischemic reserve capacity, and pericyte recruitment into the growing neovasculature can be rescued by local intramuscular delivery of an adenovirus encoding a constitutively active allele of eNOS, eNOS S1179D, but not a control virus. Collectively, our data suggest that endogenous eNOS-derived NO exerts direct effects in preserving blood flow, thereby promoting arteriogenesis, angiogenesis, and mural cell recruitment to immature angiogenic sprouts.

By the author/editor: Yu, Jun; de Muinck, Ebo D ...; Zhuang, Zhenwu; Drinane, Mary; Kauser, Katalin; Rubanyi, Gabor M ...; show more...; Qian, Hu Sheng; Murata, Takahisa; Escalante, Bruno; Sessa, William C; show less...

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