Cx37 deletion enhances vascular growth and facilitates ischemic limb recovery
Cx37 deletion enhances vascular growth and facilitates ischemic limb recovery
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DOI：
10.1152/ajpheart.00683.2011
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发表时间：
2011-11-01
影响因子：
4.8
通讯作者：
Burt, Janis M.
中科院分区：
文献类型：
--
作者：
Fang, Jennifer S.;Angelov, Stoyan N.;Burt, Janis M.
方俊山，Angelov SN，Simon AM，Burt JM。Cx37缺失可促进血管生长，促进缺血肢体恢复。Am J Physiol心圈Physiol 301：H1872-H1881,2011。2011年8月19日首次出版；doi：10.1152/ajpheart.00683.2011。-连接蛋白(Cx)37和Cx40是在血管内皮细胞中共同表达的缝隙连接形成蛋白，对组织从缺血损伤中恢复的独特贡献尚不清楚。我们最近报道，Cx37缺陷(Cx37(-/-))动物比野生型(WT)或Cx40(-/-)动物更快、更大程度地恢复缺血的后肢功能，这表明Cx37限制了WT动物的恢复。在这里，我们测试了一种假说，即增强血管生成、动脉生成和血管生成有助于改善Cx37(-/-)动物缺血后后肢的恢复。WT或Cx37(-/-)小鼠单侧后肢缺血(异氟醚麻醉)。在恢复期间记录术后肢体的外观、使用和灌注，并确定大血管和小血管的数量(和大小)。主要在胚胎发育(血管生成)期间建立的天然侧支数目也在软脑膜循环中确定。与WT组相比，Cx37(-/-)组缺血肢体腓肠肌(血管生成区)的微血管密度和股薄肌血管系统(动脉形成区)的大血管数目和弯曲程度均增加。Cx37(-/-)小鼠的软脑膜循环中侧支血管数量也增加(与WT相比)。这些结果表明，在Cx37(-/-)动物中，改善缺血后肢的恢复涉及增强血管生成，导致后肢侧支数量增加(和软膜循环)，以及更广泛的侧支重构和血管生成。这些结果与Cx37在血管系统中发挥的生长抑制效应是一致的，该效应限制了胚胎血管生成以及成年动物对缺血损伤的动脉生成和血管生成反应。
Fang JS, Angelov SN, Simon AM, Burt JM. Cx37 deletion enhances vascular growth and facilitates ischemic limb recovery. Am J Physiol Heart Circ Physiol 301: H1872-H1881, 2011. First published August 19, 2011; doi:10.1152/ajpheart.00683.2011.-The unique contributions of connexin (Cx)37 and Cx40, gap junction-forming proteins that are coexpressed in vascular endothelium, to the recovery of tissues from ischemic injury are unknown. We recently reported that Cx37-deficient (Cx37(-/-)) animals recovered ischemic hindlimb function more quickly and to a greater extent than wild-type (WT) or Cx40(-/-) animals, suggesting that Cx37 limits recovery in the WT animal. Here, we tested the hypothesis that enhanced angiogenesis, arteriogenesis, and vasculogenesis contribute to improved postischemic hindlimb recovery in Cx37(-/-) animals. Ischemia was induced unilaterally in the hindlimbs of WT or Cx37(-/-) mice (isoflurane anesthesia). Postsurgical limb appearance, use, and perfusion were documented during recovery, and the number (and size) of large and small vessels was determined. Native collateral number, predominantly established during embryonic development (vasculogenesis), was also determined in the pial circulation. Both microvascular density in the gastrocnemius of the ischemic limb (an angiogenic field) and the number and tortuosity of larger vessels in the gracilis vasculature (an arteriogenic field) were increased in Cx37(-/-) animals compared with WT animals. Cx37(-/-) mice also had an increased (vs. WT) number of collateral vessels in the pial circulation. These findings suggest that in Cx37(-/-) animals, improved recovery of the ischemic hindlimb involves enhanced vasculogenesis, resulting in increased numbers of collaterals in the hindlimb (and pial circulations) and more extensive collateral remodeling and angiogenesis. These results are consistent with Cx37 exerting a growth-suppressive effect in the vasculature that limits embryonic vasculogenesis as well as arteriogenic and angiogenic responses to ischemic injury in the adult animal.