Abstract 645: Circulating Hematopoietic Progenitor Cells are Reduced in Coronary Endothelial Dysfunction
Endothelial dysfunction is an early manifestation of vascular disease and a marker of atherosclerotic risk burden. There is growing evidence that bone marrow-derived hematopoietic stem cells may have a diagnostic and reparative role in vascular disease and may be a source of endothelial progenitors. Recent studies have shown depleted numbers of these cells both in established vascular disease and in patients with increased burden of cardiovascular risk. We hypothesized that hematopoietic stem cell numbers in circulating blood would be altered in the setting of coronary endothelial dysfunction (CED) in the absence of overt coronary disease.
Methods: Fifty consecutive patients having undergone diagnostic coronary angiography for evaluation of chest pain and without significant coronary disease were enrolled. Presence of coronary endothelial dysfunction was determined by response to intracoronary acetylcholine. Five ml of whole blood was obtained from each patient at the time of cardiac catheterization and analyzed by flow cytometry for CD34 and CD133 using ISHAGE criteria. A group of twelve patients had 50ml of whole blood drawn at the time of cardiac catheterization and buffy coat was extracted using density gradient centrifugation. This was subjected to flow cytometric analysis for CD34 and CD133 and plated on fibronectin coated wells for colony forming units (CFUs) assay analysis at 7 days.
Results: Thirty-one patients were determined to have CED as assessed by intracoronary acetylcholine challenge testing. Decreased numbers of CD34+ (whole blood, 10±1 vs 17±3 cells/100μL; buffy coat, 40±7 vs 81±11 cells/100μL, p<0.05) and CD133+ cells (33±5 vs 66±6 cells/100μL buffy coat, p<0.001), were found in patients with abnormal coronary endothelial function compared to normal respectively. The double positive CD34+/CD133+ cell count (24±6vs 47±5 cells/100μL buffy coat) and total CFU count (3±1 vs. 13±4 CFUs) were also significantly lower in patients with CED (p<0.05).
Conclusion: This is the first study to demonstrate that circulating hematopoietic progenitor cells are reduced in patients with CED. These data suggest the possibility of a mechanistic or diagnostic role for these cells in patients with this condition.