Role of endothelial progenitor cells in restenosis and progression of coronary atherosclerosis after percutaneous coronary intervention: a prospective study.

OBJECTIVES: We prospectively investigated the relationship of circulating endothelial progenitor cells at time of percutaneous coronary intervention to the subsequent development of in-stent restenosis or progression of coronary atherosclerosis.
BACKGROUND: Endothelial progenitor cells provide an endogenous repair mechanism of the dysfunctional endothelium and therefore can play a pathogenic role in coronary atherosclerosis.
METHODS: We studied 155 consecutive stable angina patients (92 men, age 60 +/- 11 years). All patients had flow cytometry the day before elective percutaneous coronary intervention in order to derive subpopulations of endothelial progenitor cells. A control group of 20 normal subjects was considered for comparison.
RESULTS: At 8-month control angiography, 30 patients showed in-stent restenosis (restenosis group), 22 patients showed progression of coronary atherosclerosis (progression group), whereas the remaining 103 patients had neither in-stent restenosis nor progression of coronary atherosclerosis (stable group). Comparison of the 3 groups did not show any difference in risk factors, cardiac morphology and function, extension of coronary artery disease, and treatment. Absolute numbers of CD34+/KDR+/CD45- cells (i.e., progenitors of endothelial lineage) measured in the restenosis group (1.41 +/- 0.64 cells/microl) were significantly higher than in the progression, stable, and control groups (1.03 +/- 0.53 cells/microl, 1.07 +/- 0.46 cells/microl, and 0.95 +/- 0.44 cells/microl, respectively, p < 0.05). Similarly, CD133+/KDR+/CD45- cells (i.e., progenitors of endothelial cells at an earlier stage) were significantly higher in the restenosis (0.63 +/- 0.23 cells/microl) compared with progression, stable, and control groups (0.33 +/- 0.19 cells/microl, 0.41 +/- 0.32 cells/microl, and 0.36 +/- 0.15 cells/microl, respectively, p < 0.001). Also, numbers of CD14+/CD45+ cells (i.e., which have a role in angiogenesis via a paracrine effect) were significantly different among the restenosis, progression, stable, and control groups (0.72 +/- 0.56 cells/microl vs. 0.51 +/- 0.52 cells/microl vs. 0.28 +/- 0.54 cells/microl vs. 0.62 +/- 0.67 cells/microl, respectively, p < 0.05), whereas CD105+/CD45-/CD34- cells (i.e., which have a receptor for transforming growth factor-beta) were similar among groups.
CONCLUSIONS: Patients with restenosis have higher numbers of subpopulations of endothelial progenitor cells that incorporate into endothelial cells or play a role in arteriogenesis compared with controls and patients with either progression of coronary atherosclerosis or stable disease. Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.