Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve
| Autor: | Takahisa Murata, Bruno Escalante, Katalin Kauser, Mary Drinane, Hu Sheng Qian, Zhenwu Zhuang, Jun Yu, Ebo D. deMuinck, William C. Sessa, Gabor M. Rubanyi |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Nitric Oxide Synthase Type III Angiogenesis Gene Expression Nitric Oxide Synthase Type II Endothelial progenitor cell Mural cell Mice Mice Congenic chemistry.chemical_compound Ischemia Enos medicine Animals Muscle Skeletal Mice Knockout Multidisciplinary Neovascularization Pathologic biology Gene Transfer Techniques Extremities Biological Sciences biology.organism_classification Cell biology Mice Inbred C57BL Vascular endothelial growth factor Nitric oxide synthase medicine.anatomical_structure chemistry Regional Blood Flow Immunology biology.protein Pericyte Arteriogenesis Nitric Oxide Synthase Pericytes |
| Zdroj: | Proceedings of the National Academy of Sciences. 102:10999-11004 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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