Role of endothelial progenitor cells in restenosis and progression of coronary atherosclerosis after percutaneous coronary intervention: a prospective study.
OBJECTIVE
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.
Department of Cardiovascular Diseases, San Filippo Neri Hospital, Rome, Italy.
Francesco
F
Pelliccia
Cinzia
C
Cianfrocca
Giuseppe
G
Rosano
Giuseppe
G
Mercuro
Giulio
G
Speciale
Vincenzo
V
Pasceri
D000071916:AC133 Antigen; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D019070:Cell Lineage; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D023903:Coronary Restenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D018450:Disease Progression; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D011446:Prospective Studies; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood
D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D040301:Vascular Endothelial Growth Factor Receptor-2; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human