Proportional Relationship Between Early Mobilization Of Bone Marrow Progenitor Cells And The Extent Of Vascular Injury During Coronary Stenting: Insights On The Role Of Systemic Mechanisms Of Vascular

Abstract Background The role of circulating progenitor cells (CPCs) on vascular repair after everolimus-eluting stent (EES) implantation is largely unknown. Objectives The aim of the study was to investigate the quantitative and temporal variations of CPCs levels after EES implantation, and its relationship with the degree of peri-procedural vascular damage, stent healing and neointimal hyperplasia, as measured by optical coherence tomography (OCT). Methods In a consecutive series of patients with stable coronary artery disease undergoing stent implantation CPC subpopulations (CD34+/CD45low, CD133+/CD45low, CD34/KDR/CD45low, CD133/KDR/CD45low) were evaluated using a flow cytometry technique at baseline, 1 and 4 weeks. OCT evaluation was performed immediately after stent implantation to quantify stenting-related injury, and at 9-month follow-up to assess mid-term vascular response. Results Twenty patients (mean age 66±9 years; 80%male) with 24 stenoses treated with EES were included in the study. Vascular injury score was associated with the increase of CD133+/KDR/CD45 low at 1-week (β0.28 [95% CI0.15; 0.41], p<0.001) and with the maximum neointimal thickness at 9-month follow-up (β0.008 [95% CI-0.0004; 0.002]:p=0.04). Mean neointimal area at 9-month was associated with the increase in the number of CD34+/CD45low at 1 week (β0.029 [95% CI0.025;-0.033]; p<0.0001). Inverse relationships between the number of uncoated and apposed struts at 9-month and the 1-week delta values of CD34/KDR/CD45low and CD133/KDR/CD45low (β-4.49 [95% CI-8.17;-0.82]; p=0.017 and β −12.53 [95% CI: −22.17; −2.90]; p=0.011, respectively) were also found. Conclusion Long-term vascular healing after EES implantation is modulated by early changes in levels of CPC subpopulations. This systemic response is proportional to the extent of vessel wall injury. Early mobilization of CPCs influences mid-term strut coverage and the development of neointimal hyperplasia. Acknowledgement/Funding Dr Jimenez-Quevedo is a recipient of the ISCIII (Instituto de Salud Carlos III) grant “Fondo de Investigaciόn Sanitaria” (PI11/00299) to perform this