Suppressed hindlimb perfusion in Rac2-/- and Nox2-/- mice does not result from impaired collateral growth
Suppressed hindlimb perfusion in Rac2-/- and Nox2-/- mice does not result from impaired collateral growth
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DOI：
10.1152/ajpheart.00772.2008
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发表时间：
2009-03-01
影响因子：
4.8
通讯作者：
Unthank, Joseph L.
中科院分区：
文献类型：
--
作者：
Distasi, Matthew R.;Case, Jamie;Unthank, Joseph L.
Distasi MR，Case J，齐格勒MA，Dinauer MC，Yoder MC，Haneline LS，Dalsing MC，米勒SJ，Labelre CA，Murphy MP，Ingram DA，Unthank JL. Rac 2（-/-）和Nox 2（-/-）小鼠的后肢灌注受抑制并非由侧枝生长受损所致。Am J Physiol Heart Circ Physiol 296：H877-H886，2009。首次发表于2009年1月16日; doi：10.1152/ajpheart.00772.2008。虽然在NADPH氧化酶2（Nox 2）-null（Nox 2（-/-））小鼠中，急性股动脉闭塞后的组织灌注和血管生成受到抑制，但研究尚未确定Nox 2在侧支动脉扩张中的作用。Rac 2是一种小的GT3，它结合Nox 2并激活基于Nox 2的NAD（P）H氧化酶，但与Nox 2不同，Rac 2主要限于骨髓来源的细胞。在这项研究中，我们使用Rac 2-null（Rac 2（-/-））和Nox 2（-/-）小鼠与一种新的方法，确定主要后肢侧支研究的假设，侧支生长需要这些分子。当采用股动脉结扎进行的初始实验表明Rac 2（-/-）和野生型C57 BL/6 J（BL 6）小鼠的灌注和侧支生长相似时，随后采用更严重的缺血模型（股动脉切除）进行了实验。股骨切除后，相对于BL 6小鼠，Rac 2（-/-）小鼠的组织灌注受到抑制。包括坏死和再生肌纤维以及脂质和胶原沉积在内的缺血性损伤的组织学评估表明Rac 2（-/-）小鼠的损伤更大。在BL 6和Rac 2（-/-）小鼠中，用活体显微镜在Microfil注射期间鉴定的原发侧支直径扩大到相似的程度。两种品系的侧支横截面中的内膜细胞数量增加，并且为CD 31阳性和CD 45阴性。Rac 2（-/-）动物的循环白细胞和CD 11b（+）细胞增加幅度大于BL 6动物。在Nox 2（-/-）小鼠中进行的实验验证了与侧枝生长相关的非预期结果并非Rac 2（-/-）小鼠所独有，得到了等效结果。数据表明，急性股动脉切除后，Rac 2（-/-）和Nox 2（-/-）小鼠的灌注恢复受损，但侧支管腔扩张和内膜细胞募集/增殖正常。这些新的结果表明，侧支管腔扩张和内膜细胞募集/增殖不是由Rac 2和Nox 2介导的。
Distasi MR, Case J, Ziegler MA, Dinauer MC, Yoder MC, Haneline LS, Dalsing MC, Miller SJ, Labarrere CA, Murphy MP, Ingram DA, Unthank JL. Suppressed hindlimb perfusion in Rac2(-/-) and Nox2(-/-) mice does not result from impaired collateral growth. Am J Physiol Heart Circ Physiol 296: H877-H886, 2009. First published January 16, 2009; doi:10.1152/ajpheart.00772.2008.-While tissue perfusion and angiogenesis subsequent to acute femoral artery occlusion are suppressed in NADPH oxidase 2 (Nox2)-null (Nox2(-/-)) mice, studies have not established the role of Nox2 in collateral artery enlargement. Rac2 is a small GTPase that binds Nox2 and activates Nox2-based NAD(P) H oxidase but, unlike Nox2, is primarily restricted to bone marrow-derived cells. In this study, we used Rac2-null (Rac2(-/-)) and Nox2(-/-) mice with a novel method of identifying primary hindlimb collaterals to investigate the hypothesis that collateral growth requires these molecules. When initial experiments performed with femoral ligation demonstrated similar perfusion and collateral growth in Rac2(-/-) and wild-type C57BL/6J (BL6) mice, subsequent experiments were performed with a more severe ischemia model, femoral artery excision. After femoral excision, tissue perfusion was suppressed in Rac2(-/-) mice relative to BL6 mice. Histological assessment of ischemic injury including necrotic and regenerated muscle fibers and lipid and collagen deposition demonstrated greater injury in Rac2(-/-) mice. The diameters of primary collaterals identified during Microfil injection with intravital microscopy were enlarged to a similar extent in BL6 and Rac2(-/-) mice. Intimal cells in collateral cross sections were increased in number in both strains and were CD31 positive and CD45 negative. Circulating leukocytes and CD11b(+) cells were increased more in Rac2(-/-) than BL6 animals. Experiments performed in Nox2(-/-) mice to verify that the unexpected results related to collateral growth were not unique to Rac2(-/-) mice gave equivalent results. The data demonstrate that, subsequent to acute femoral artery excision, perfusion recovery is impaired in Rac2(-/-) and Nox2(-/-) mice but that collateral luminal expansion and intimal cell recruitment/proliferation are normal. These novel results indicate that collateral luminal expansion and intimal cell recruitment/proliferation are not mediated by Rac2 and Nox2.