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

JACC Cardiovasc Interv. 2010 Jan;3(1):78-86. doi: 10.1016/j.jcin.2009.10.020.

Abstract

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.

MeSH terms

  • AC133 Antigen
  • Aged
  • Angioplasty, Balloon, Coronary* / adverse effects
  • Antigens, CD / blood
  • Biomarkers / blood
  • Case-Control Studies
  • Cell Lineage
  • Coronary Angiography
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / pathology
  • Coronary Artery Disease / therapy*
  • Coronary Restenosis / blood
  • Coronary Restenosis / diagnostic imaging
  • Coronary Restenosis / etiology
  • Coronary Restenosis / pathology*
  • Disease Progression
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Female
  • Flow Cytometry
  • Glycoproteins / blood
  • Humans
  • Leukocyte Common Antigens / blood
  • Male
  • Middle Aged
  • Peptides / blood
  • Prospective Studies
  • Stem Cells / immunology
  • Stem Cells / metabolism
  • Stem Cells / pathology*
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor Receptor-2 / blood

Substances

  • AC133 Antigen
  • Antigens, CD
  • Biomarkers
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Vascular Endothelial Growth Factor Receptor-2
  • Leukocyte Common Antigens
  • PTPRC protein, human