Endothelial nitric oxide synthase affects both early and late collateral arterial adaptation and blood flow recovery after induction of hind limb ischemia in mice.

Endothelial nitric oxide synthase affects both early and late collateral arterial adaptation and blood flow recovery after induction of hind limb ischemia in mice.
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DOI:
10.1016/j.jvs.2009.08.045
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发表时间:
2010-01
影响因子:
4.3
通讯作者:
Messina, Louis M.
Messina, Louis M.
中科院分区:
医学2区
文献类型:
--
作者:
Park, Brian;Hoffman, Ari;Yang, Yagai;Yan, Jinglian;Tie, Guodong;Bagshahi, Hossein;Nowicki, Philip T.;Messina, Louis M.

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本研究的目的是确定内皮一氧化氮合酶(eNOS)是否影响严重肢体缺血后早期和晚期侧支动脉适应和血流恢复,并确定eNOS衍生的NO是否是招募CXCR 4 + VEGFR 1+血管细胞所必需的。缺血部位。进行了两项研究。在第一项研究中,在3组中通过单侧股动脉切除诱导后肢缺血:C57 B1 6(野生型)、eNOS-/-和C57 B1/6小鼠,从切除前1天到切除后3天(早期L-NAME组)用L-NAME处理。在诱导缺血后第3天对这3组进行研究。在第二项研究中,在2组中诱导后肢缺血:C57 B1/6小鼠(野生型)和在诱导缺血后第3天至第28天用L-NAME处理的C57 B1/6小鼠。两组均于缺血后第28天进行观察。因变量包括后肢灌注,侧支动脉直径,缺血后肢内血管细胞的数量和位置。在第一项研究中,eNOS-/-和早期L-NAME治疗组在缺血的第2天发生脚趾坏疽。与野生型组相比,这些组表现出较少的血流恢复和较小的侧支动脉直径。血管细胞存在于野生型组侧支动脉的外膜内,但在eNOS-/-和早期L-NAME治疗组中仅以随机模式稀疏存在。在第二项研究中,晚期L-NAME组在缺血的第28天表现出比野生型组更少的血流恢复和更小的侧支动脉直径。在野生型组中,血管细胞呈毛细血管周围分布,但在晚期L-NAME治疗组中仅稀疏存在。eNOS衍生的NO对于后肢缺血的早期(第3天)和晚期(第28天)适应性反应都是必需的。NO是正常血管细胞募集到缺血组织所必需的。
The goals of this study were to determine if endothelial nitric oxide synthase (eNOS) affects both early and late collateral arterial adaptation and blood flow recovery after severe limb ischemia, and to determine if eNOS-derived NO was necessary for recruitment of CXCR4+ VEGFR1+ hemangiocytes to the site of ischemia. Two studies were carried out. In the first study, hindlimb ischemia was induced by unilateral femoral artery excision in 3 groups: C57Bl6 (wild type), eNOS-/-, and C57Bl/6 mice treated with L-NAME from 1 day prior to excision through day 3 after excision (early L-NAME group). These 3 groups were studied on the 3rd day after induction of ischemia. In the second study, hindlimb ischemia was induced in 2 groups: C57Bl/6 mice (wild type) and C57Bl/6 mice treated with L-NAME from the 3rd through the 28th day after induction of ischemia. These 2 groups were studied on the 28th day after induction of ischemia. Dependent variables included hindlimb perfusion, collateral artery diameter, and the number and location of hemangiocytes within the ischemic hindlimb. In the first study, the eNOS-/- and early L-NAME treatment groups developed toe gangrene by the 2nd day of ischemia. These groups demonstrated less blood flow recovery and smaller collateral artery diameter than the wild type group. Hemangiocytes were present within the adventitia of collateral arteries in the wild type group, but were only sparsely present, in a random pattern, in the eNOS-/- and early L-NAME treatment groups. In the second study, the late L-NAME group showed less blood flow recovery and smaller collateral artery diameter on the 28th day of ischemia than the wild type group. Hemangiocytes were present in a peri-capillary distribution in the wild type group, but present only sparsely in the late L-NAME treatment group. eNOS-derived NO is necessary for both the early (day 3) and late (day 28) adaptive responses to hindlimb ischemia. NO is necessary for normal hemangiocyte recruitment to the ischemic tissue.
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发表时间: 1997-04-15
期刊: CIRCULATION
影响因子: 37.8
作者:
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发表时间: 2003-11-01
期刊: NATURE MEDICINE
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发表时间: 2003-10-01
影响因子: 4.3
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影响因子: 4.3
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