Bruce Anthony C, Kelly-Goss Molly R, Heuslein Joshua L, Meisner Joshua K, Price Richard J, Peirce Shayn M
From the Department of Biomedical Engineering, University of Virginia, Charlottesville.
Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):2012-22. doi: 10.1161/ATVBAHA.114.303399. Epub 2014 Jun 26.
Chronic arterial occlusion results in arteriogenesis of collateral blood vessels. This process has been shown to be dependent on the recruitment of growth-promoting macrophages to remodeling collaterals. However, the potential role of venules in monocyte recruitment during microvascular arteriogenesis is not well demonstrated. First, we aim to document that arteriogenesis occurs in the mouse spinotrapezius ligation model. Then, we investigate the temporal and spatial distribution, as well as proliferation, of monocytes/macrophages recruited to collateral arterioles in response to elevated fluid shear stress.
Laser speckle flowmetry confirmed a postligation increase in blood velocity within collateral arterioles but not within venules. After 72 hours post ligation, collateral arteriole diameters were increased, proliferating cells were identified in vessel walls of shear-activated collaterals, and perivascular CD206(+) macrophages demonstrated proliferation. A 5-ethynyl-2'-deoxyuridine assay identified proliferation. CD68(+)CD206(+) cells around collaterals were increased 96%, whereas CX3CR1((+/GFP)) cells were increased 126% in ligated versus sham groups after 72 hours. CX3CR1((+/GFP)) cells were predominately venule associated at 6 hours after ligation; and CX3CR1((+/GFP hi)) cells shifted from venule to arteriole associated between 6 and 72 hours after surgery exclusively in ligated muscle. We report accumulation and extravasation of adhered CX3CR1((+/GFP)) cells in and from venules, but not from arterioles, after ligation.
Our results demonstrate that arteriogenesis occurs in the murine spinotrapezius ligation model and implicate postcapillary venules as the site of tissue entry for circulating monocytes. Local proliferation of macrophages is also documented. These data open up questions about the role of arteriole-venule communication during monocyte recruitment.
慢性动脉闭塞会导致侧支血管的动脉生成。这一过程已被证明依赖于招募促进生长的巨噬细胞至重塑的侧支血管。然而，在微血管动脉生成过程中，小静脉在单核细胞招募中的潜在作用尚未得到充分证实。首先，我们旨在证明在小鼠斜方肌结扎模型中发生了动脉生成。然后，我们研究响应于升高的流体剪切应力而招募到侧支小动脉的单核细胞/巨噬细胞的时间和空间分布以及增殖情况。
激光散斑血流仪证实结扎后侧支小动脉内的血流速度增加，但小静脉内未增加。结扎后72小时，侧支小动脉直径增加，在剪切激活的侧支血管壁中鉴定出增殖细胞，并且血管周围CD206(+)巨噬细胞显示出增殖。5-乙炔基-2'-脱氧尿苷检测确定了增殖情况。与假手术组相比，结扎后72小时，侧支周围的CD68(+)CD206(+)细胞增加了96%，而CX3CR1((+/GFP))细胞增加了126%。结扎后6小时，CX3CR1((+/GFP))细胞主要与小静脉相关；而CX3CR1((+/GFP hi))细胞在手术后6至72小时之间从小静脉转移至仅在结扎肌肉中的与小动脉相关。我们报告结扎后，黏附的CX3CR1((+/GFP))细胞在小静脉中积聚并从小静脉外渗，但不是从小动脉外渗。
我们的结果表明在小鼠斜方肌结扎模型中发生了动脉生成，并表明毛细血管后小静脉是循环单核细胞进入组织的部位。还记录了巨噬细胞的局部增殖。这些数据引发了关于在单核细胞招募过程中动脉-静脉通讯作用的问题。
