Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve
Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve
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DOI：
10.1073/pnas.0501444102
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发表时间：
2005-08-02
影响因子：
11.1
通讯作者：
Sessa, WC
中科院分区：
文献类型：
--
作者：
Yu, J;deMuinck, ED;Sessa, WC
小鼠内皮源性一氧化氮合酶（eNOS）的遗传缺失会损害血管内皮生长因子（VEGF）和缺血引发的血流恢复，导致严重肢体缺血。这种结果可能是由于动脉生成、血管生成或干细胞和祖细胞的动员受损所致。在这里，我们发现缺血刺激后，eNOS敲除小鼠[eNOS(-/-)]在肌肉刺激和周细胞募集后的动脉生成和功能性血流储备方面存在缺陷，但内皮祖细胞募集方面没有损伤。更重要的是，通过局部肌内递送一种腺病毒（编码eNOS S1179D构成型活性等位基因），而不是对照病毒，可以挽救血流恢复缺陷、缺血临床表现、缺血储备能力和周细胞募集到生长中的新血管中。总的来说，我们的数据表明，内源性enos衍生的NO在保持血流方面具有直接作用，从而促进动脉生成、血管生成和壁细胞向未成熟血管生成芽的募集。
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.