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Role of Endothelial Progenitor Cells in Restenosis and Progression of Coronary Atherosclerosis After Percutaneous Coronary Intervention

A Prospective Study

Francesco Pelliccia, MD, PhD^_*,, Cinzia Cianfrocca, MD^_*,, Giuseppe Rosano, MD, PhD, Giuseppe Mercuro, MD, Giulio Speciale, MD^_*, Vincenzo Pasceri, MD, PhD^_*,_*

^_* Department of Cardiovascular Diseases, San Filippo Neri Hospital, Rome, Italy
Department of Medical Sciences, Istituto di Ricovero Cura a Carrettere Scientifico San Raffaele Pisana, Rome, Italy
Department of Cardiovascular and Neurologic Diseases, University of Cagliari, Cagliari, Italy

^_* Reprint requests and correspondence: Dr. Vincenzo Pasceri, Cardiovascular Department, San Filippo Neri Hospital, Via G. Martinotti 20, 00135 Rome, Italy (Email: vpasceri{at}hotmail.com).

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/µl) were significantly higher than in the progression, stable, and control groups (1.03 ± 0.53 cells/µl, 1.07 ± 0.46 cells/µl, and 0.95 ± 0.44 cells/µl, 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/µl) compared with progression, stable, and control groups (0.33 ± 0.19 cells/µl, 0.41 ± 0.32 cells/µl, and 0.36 ± 0.15 cells/µl, 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/µl vs. 0.51 ± 0.52 cells/µl vs. 0.28 ± 0.54 cells/µl vs. 0.62 ± 0.67 cells/µl, 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.

Key Words: angiogenesis • endothelial progenitor cells • percutaneous coronary intervention • restenosis • stem cells

Abbreviations and Acronyms   EPC = endothelial progenitor cell   PCI = percutaneous coronary intervention

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Robbert J. De Winter and Margo Klomp
J. Am. Coll. Cardiol. Intv. 2010 3: 87-89. [Full Text] [PDF]

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