Westvik Tormod S, Fitzgerald Tamara N, Muto Akihito, Maloney Stephen P, Pimiento Jose M, Fancher Tiffany T, Magri Dania, Westvik Hilde H, Nishibe Toshiya, Velazquez Omaida C, Dardik Alan
Departments of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8089, USA.
J Vasc Surg. 2009 Feb;49(2):464-73. doi: 10.1016/j.jvs.2008.08.077. Epub 2008 Nov 22.
Older patients are thought to tolerate acute ischemia more poorly than younger patients. Since aging may depress both angiogenesis and arteriogenesis, we determined the effects of age on both angiogenesis and arteriogenesis in a model of severe acute limb ischemia.
Young adult (3-months-old) and aged (18-months-old) C57BL/6 mice underwent right common iliac artery and vein ligation and transection. Data were collected on days 0, 7, and 14. Perfusion was measured with a laser Doppler scan and compared to the contralateral limb. Functional deficits were evaluated with the Tarlov scale. Capillary density and endothelial progenitor cell (EPC) number were determined by direct counting lectin-positive/alpha-actin-negative cells and VEGFR2/CXCR4 dually-positive cells, respectively; angiography was performed to directly assess arteriogenesis.
Young adult and aged mice had a similar degree of decreased perfusion after iliac ligation (young, n = 15: 20.4 +/- 1.9%, vs aged, n = 20: 19.6 +/- 1.3%; P = .72, analysis of variance [ANOVA]); however, young mice recovered faster and to a greater degree than aged mice (day 7, 35 +/- 6% vs 17 +/- 4%, P = .046; day 14, 60 +/- 5% vs 27 +/- 7%, P = .0014). Aged mice had worse functional recovery by day 14 compared to young mice (2.3 +/- 0.3 vs 4.3 +/- 0.4; P = .0021). Aged mice had increased capillary density (day 7, 12.9 +/- 4.4 vs 2.8 +/- 0.3 capillaries/hpf; P = .02) and increased number of EPC incorporated into the ischemic muscle (day 7, 8.1 +/- 0.9 vs 2.5 +/- 1.9 cells; P = .007) compared to young mice, but diminished numbers of collateral vessels to the ischemic limb (1 vs 9; P = .01), as seen on angiography.
After severe hind limb ischemia, aged animals become ischemic to a similar degree as young animals, but aged animals have significantly impaired arteriogenesis and functional recovery compared to younger animals. These results suggest that strategies to stimulate arteriogenesis may complement those that increase angiogenesis, and may result in improved relief of ischemia.
一般认为老年患者对急性缺血的耐受性比年轻患者差。由于衰老可能会抑制血管生成和动脉生成，我们在严重急性肢体缺血模型中确定了年龄对血管生成和动脉生成的影响。
对年轻成年（3个月大）和老年（18个月大）的C57BL/6小鼠进行右髂总动脉和静脉结扎及横断。在第0、7和14天收集数据。用激光多普勒扫描测量灌注，并与对侧肢体进行比较。用塔尔洛夫量表评估功能缺陷。分别通过直接计数凝集素阳性/α-肌动蛋白阴性细胞和VEGFR2/CXCR4双阳性细胞来确定毛细血管密度和内皮祖细胞（EPC）数量；进行血管造影以直接评估动脉生成。
年轻成年小鼠和老年小鼠在髂动脉结扎后灌注降低的程度相似（年轻组，n = 15：20.4 +/- 1.9%，老年组，n = 20：19.6 +/- 1.3%；P = 0.72，方差分析[ANOVA]）；然而，年轻小鼠恢复得更快且程度更大（第7天，35 +/- 6%对17 +/- 4%，P = 0.046；第14天，60 +/- 5%对27 +/- 7%，P = 0.0014）。与年轻小鼠相比，老年小鼠在第14天时功能恢复更差（2.3 +/- 0.3对4.3 +/- 0.4；P = 0.0021）。与年轻小鼠相比，老年小鼠的毛细血管密度增加（第7天，12.9 +/- 4.4对2.8 +/- 0.3条毛细血管/高倍视野；P = 0.02），且缺血肌肉中整合的EPC数量增加（第7天，8.1 +/- 0.9对2.5 +/- 1.9个细胞；P = 0.007），但如血管造影所见，缺血肢体的侧支血管数量减少（1对9；P = 0.01）。
在严重后肢缺血后，老年动物缺血程度与年轻动物相似，但与年轻动物相比，老年动物的动脉生成和功能恢复明显受损。这些结果表明，刺激动脉生成的策略可能补充增加血管生成的策略，并可能改善缺血缓解情况。
