Arteriolar remodeling following ischemic injury extends from capillary to large arteriole in the microcirculation

Arteriolar remodeling following ischemic injury extends from capillary to large arteriole in the microcirculation
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DOI:
10.1080/10739680701708436
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发表时间:
2008-01-01
期刊:
影响因子:
2.4
通讯作者:
Peirce, Shayn M.
Peirce, Shayn M.
中科院分区:
医学4区
文献类型:
--
作者:
Bailey, Alexander M.;O'Neill, Thomas J.;Peirce, Shayn M.

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目的:骨骼肌血管在失血后通过动脉生成来恢复组织的灌注和功能。尽管最近的研究表明,这一过程也可能发生在微循环中,但这一过程已被证明发生在缺血后的大血管中。我们在毛细血管到直径35微米以下的小动脉尺度上验证了缺血诱导骨骼肌微循环微血管重构的假说。方法:在C57BL/6小鼠上,将供血小动脉与棘斜方肌尾半部结扎。5天后,用活体和整体共聚焦显微镜对微血管重塑反应进行量化。免疫组织化学染色显示血管、结合的白细胞和缺氧区。结果:缺血组织发生了局部的微血管重构,包括明显的血管曲折。在开放的微血管(直径15-35微米)中,我们观察到血管密度(38%)、分支(90%)和侧支发育(36.5%)增加。新的微动脉(直径6~35微米)的形成增加了24.3%,而所有组织均未出现慢性缺氧。结论:缺血损伤可诱导骨骼肌微循环中的动脉生成。此外,这种手术模型能够以单细胞分辨率进行微循环适应的面部分析,并可以为研究人员提供微尺度的形态测量数据,这是使用其他模型难以实现的。
Objective: Skeletal muscle vasculature undergoes arteriogenesis to restore tissue perfusion and function following loss of blood flow. This process has been shown to occur in large vessels following ischemia, although recent studies suggest this may occur in the microcirculation as well. We tested the hypothesis that ischemia induces microvascular remodeling in the skeletal muscle microcirculation on the scale of capillary to sub-35 mu m diameter arterioles.Methods: Ligations of a feeding arteriole to the caudal-half of the spinotrapezius muscle were performed on C57BL/6 mice. At 5 days, microvascular remodeling responses were quantified using intravital and whole-mount confocal microscopy. Immunohistochemistry was performed to visualize vessels, incorporated leukocytes, and regions of hypoxia.Results: Ischemic tissue underwent localized microvascular remodeling characteristic of arteriogenesis, including pronounced vessel tortuosity. In patent microvessels (diameters 15-35 mu m), we observed increases in vascular density (38%), branching (90%) and collateral development (36.5%). The formation of new arterioles (diameters 6-35 mu m) increased by 24.3%, while chronic hypoxia was absent from all tissues.Conclusions: Ischemic injury induces arteriogenesis in skeletal muscle microcirculation. Furthermore, this surgical model enables en face analysis of microcirculatory adaptations with single-cell resolution and can provide investigators with morphometric data on a microscale that is difficult to achieve using other models.