on October 20, 2003
Published online before print October 20, 2003, doi: 10.1161/01.CIR.0000097001.79750.78
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Submitted on January 27, 2003
From the Department of Internal Medicine (H.-J.C., H.-S.K., M.-M.L., D.-H.K., K.-K.H., S.O., I.-H.C., B.-H.O., Y.-S.C., Y.-B.P.), Seoul National University College of Medicine; Department of Internal Medicine (Y.-J.C.), Hallym University College of Medicine; and Cardiovascular Research Laboratory (J.-J.C., H.-S.K., M.-M.L., D.-H.K., H.-J.Y., J.H., K.-K.H., S.O., I.-H.C., B.-H.O., Y.-S.C. Y.-B.P.), Clinical Research Institute, Seoul National University Hospital, Korea; and Whitaker Cardiovascular Institute (H.-S.K., K.W.), Boston University School of Medicine, Boston, Mass. * To whom correspondence should be addressed. E-mail: hyosoo{at}snu.ac.kr.
Background--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. Methods and Results--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 µg/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). Conclusions--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.
Revised on July 29, 2003
Accepted on July 30, 2003
Mobilized Endothelial Progenitor Cells by Granulocyte-Macrophage Colony-Stimulating Factor Accelerate Reendothelialization and Reduce Vascular Inflammation After Intravascular Radiation
Hyun-Jai Cho MD,
Key words: endothelium • angioplasty • restenosis • radioisotopes
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