Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia

Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia
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DOI:
10.1152/ajpheart.00004.2011
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发表时间:
2011-06-01
影响因子:
4.8
通讯作者:
Burnett, Mary Susan
Burnett, Mary Susan
中科院分区:
医学2区
文献类型:
--
作者:
Peng, XinZhi;Wang, Jinsong;Burnett, Mary Susan

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彭新,王杰,lassence - soares RM, Najafi AH, ood S, Aghili N, Alderman LO, Panza JA, Faber JE, Wang S, Epstein SE, Burnett MS.性别差异对小鼠后肢缺血模型血流恢复的影响。[J] .中国生物医学工程学报,2011,31(2):557 - 557。首次发表于2011年3月11日;doi: 10.1152 / ajpheart.00004.2011。-缺血组织血流恢复受多种危险因素影响。本研究的目的是研究性别对小鼠后肢缺血模型动脉生成和血管生成的影响。C57BL/6J小鼠单侧后肢缺血。女性血流恢复较少,后肢使用障碍较大。尽管术后7天女性内收肌区中点的α -平滑肌肌动蛋白阳性血管较少,但在基线时血管数量没有发现性别差异。女性后肢血管阻力较高,对血管扩张剂反应较差,对结扎后血管收缩剂更敏感。Western blotting显示,雌性犊牛的血管内皮生长因子(VEGF)和内皮型一氧化氮合酶(eNOS)基线水平较高,而结扎后7天雄性犊牛的VEGF、eNOS和磷酸化血管扩张剂刺激磷酸化蛋白水平较高。在体外基质塞实验中,女性血管生成较少,内皮细胞增殖较少。女性血流恢复受损,这一发现可能是由多种因素引起的,包括侧支重塑减少、血管生成减少、血管舒张反应受损和血管收缩活性增加;我们的结果还表明,新的侧枝形成的可能性,从毛细血管,是受损的女性。
Peng X, Wang J, Lassance-Soares RM, Najafi AH, Sood S, Aghili N, Alderman LO, Panza JA, Faber JE, Wang S, Epstein SE, Burnett MS. Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia. Am J Physiol Heart Circ Physiol 300: H2027-H2034, 2011. First published March 11, 2011; doi: 10.1152/ajpheart.00004.2011.-Blood flow restoration to ischemic tissue is affected by various risk factors. The aim of this study was to examine gender effects on arteriogenesis and angiogenesis in a mouse ischemic hindlimb model. C57BL/6J mice were subjected to unilateral hindlimb ischemia. Flow recovery was less and hindlimb use impairment was greater in females. No gender difference in vessel number was found at baseline, although 7 days postsurgery females had fewer alpha-smooth muscle actin-positive vessels in the midpoint of the adductor region. Females had higher hindlimb vascular resistance, were less responsive to vasodilators, and were more sensitive to vasoconstrictors postligation. Western blotting showed that females had higher baseline levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in the calf, while 7 days postligation males had higher levels of VEGF, eNOS, and phosphorylated vasodilator stimulated phosphoprotein. Females had less angiogenesis in a Matrigel plug assay and less endothelial cell proliferation in vitro. Females have impaired recovery of flow, a finding presumably caused by multiple factors including decreased collateral remodeling, less angiogenesis, impaired vasodilator response, and increased vasoconstrictor activity; our results also suggest the possibility that new collateral formation, from capillaries, is impaired in females.