Cho Hyun-Jai, Kim Hyo-Soo, Lee Myoung-Mook, Kim Dae-Hee, Yang Hyun-Ju, Hur Jin, Hwang Kyoung-Kook, Oh Seil, Choi Young-Jin, Chae In-Ho, Oh Byung-Hee, Choi Yun-Shik, Walsh Kenneth, Park Young-Bae
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Korea.
Circulation. 2003 Dec 9;108(23):2918-25. doi: 10.1161/01.CIR.0000097001.79750.78. Epub 2003 Oct 20.
Endothelial progenitor cells (EPCs) play a pivotal role in repair and regeneration of damaged vessels. We investigated the role of mobilized EPCs in the healing process after intravascular radiation therapy.
One iliac artery of hypercholesterolemic rabbits was subjected to balloon injury and intravascular radiation with a Re-188 balloon and the contralateral iliac artery to balloon injury only. Rabbits received granulocyte-macrophage colony-stimulating factor (recombinant human GM-CSF) (60 microg/d subcutaneously) daily for 1 week, either 7 days before the angioplasty or at the time of angioplasty. Control rabbits received human albumin. GM-CSF significantly increased the double-positive (CD31+ and KDR+) fraction in peripheral blood monocytes and showed a higher number of EPCs than albumin after culture and, furthermore, enhanced migration and incorporation of EPCs. In the albumin group, intravascular radiation therapy reduced neointimal hyperplasia but delayed reendothelialization and aggravated monocyte infiltration. GM-CSF treatment significantly accelerated the reendothelialization and inhibited monocyte infiltration (reendothelialization index, 81+/-13% in the GM-CSF radiation [n=7] versus 30+/-11% in the control radiation [n=9] at 2 weeks, P<0.01). GM-CSF treatment produced an additional significant reduction in neointimal formation at 14 and 28 days after injury in the intravascular radiation groups (intima to media ratio, 0.14+/-0.11 in the GM-CSF radiation [n=5] versus 0.36+/-0.07 in the control radiation [n=5] at 4 weeks, P<0.01).
GM-CSF treatment mobilizes EPCs, accelerates reendothelialization, and reduces monocytes infiltration after intravascular radiation therapy, suggesting that stem cell mobilization is a promising strategy for enhancing the vascular healing process after cytotoxic angioplasty.
内皮祖细胞（EPCs）在受损血管的修复和再生中起关键作用。我们研究了动员的EPCs在血管内放射治疗后愈合过程中的作用。
对高胆固醇血症兔的一侧髂动脉进行球囊损伤并用Re-188球囊进行血管内放射治疗，对侧髂动脉仅进行球囊损伤。兔子在血管成形术前7天或血管成形术时每天皮下注射粒细胞巨噬细胞集落刺激因子（重组人GM-CSF）（60μg/d），持续1周。对照兔注射人白蛋白。GM-CSF显著增加外周血单核细胞中双阳性（CD31+和KDR+）比例，培养后显示出比白蛋白组更多的EPCs，此外，还增强了EPCs的迁移和整合。在白蛋白组中，血管内放射治疗减少了内膜增生，但延迟了内皮再形成并加重了单核细胞浸润。GM-CSF治疗显著加速了内皮再形成并抑制了单核细胞浸润（2周时，GM-CSF放射组的内皮再形成指数为81±13%[n=7]，对照放射组为30±11%[n=9]，P<0.01）。在血管内放射组中，GM-CSF治疗在损伤后14天和28天内膜形成有额外显著减少（4周时，GM-CSF放射组的内膜中膜比为0.14±0.11[n=5]，对照放射组为0.36±0.07[n=5]，P<0.01）。
GM-CSF治疗可动员EPCs，加速血管内放射治疗后的内皮再形成并减少单核细胞浸润，提示干细胞动员是增强细胞毒性血管成形术后血管愈合过程的一种有前景的策略。
