Thomas G Nührenberg1, Min Zhao2, Christian Stratz2, Michael Amann2, Christian M Valina2, Michael Gick2, Dietmar Trenk2, Harald Binder3, Heinz Joachim Büttner2, Franz-Josef Neumann2. 1. Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany. Electronic address: thomas.nuehrenberg@universitaets-herzzentrum.de. 2. Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany. 3. Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre Johannes Gutenberg University Mainz, D-55101 Mainz, Germany.
Abstract
OBJECTIVES: This study assessed whether different subsets of circulating endothelial and putative endothelial progenitor cells (CEC and EPC) correlate with stent strut coverage (SSC) using second generation optical coherence tomography (OCT). BACKGROUND: Due to the lack of imaging modalities with a resolution down to the magnitude of a few cells, the influence of EPC on endothelialisation of drug-eluting stents has not been assessed in patients. METHODS: In 37 patients, SSC of everolimus-eluting stents was assessed by OCT 5-7months after stent implantation. Different subsets of EPC (CD34(+)KDR(+), CD34(+)KDR(+)CD45(dim), CD133(+), CD3(+)CD31(+)), CEC (CD31(+)CD45(-)CD146(+)), and CD31(+)CD45(-)CD146(-) representing large platelets were analysed by flow cytometry, including viability analyses with 7-AAD. Statistical analysis comprised univariate regression analysis and multivariable models integrating OCT and flow cytometry data as well as clinical variables. RESULTS: SSC and frequency of different cell types were highly comparable with previously published data. EPC defined in part by KDR expression were mostly non-viable. On univariate and in multivariable models, no association between EPC counts and strut coverage was detected. For CD31(+)CD45(-)CD146(-) counts, representing large platelets, an inverse relationship with strut coverage was identified by a multivariable regression model adjusting for age, sex, diabetes mellitus, NYHA and CCS class, CRP, serum triglycerides, glucose and creatinine (beta=-9.42, p=0.006). CONCLUSIONS: There was no significant association between EPC or CEC and healing after drug-eluting stent implantation. Yet, CD31(+)CD45(-)CD146(-) cells were associated with low SSC. These data suggest that large platelets may represent a more important mediator of late stent endothelialisation than EPC.
OBJECTIVES: This study assessed whether different subsets of circulating endothelial and putative endothelial progenitor cells (CEC and EPC) correlate with stent strut coverage (SSC) using second generation optical coherence tomography (OCT). BACKGROUND: Due to the lack of imaging modalities with a resolution down to the magnitude of a few cells, the influence of EPC on endothelialisation of drug-eluting stents has not been assessed in patients. METHODS: In 37 patients, SSC of everolimus-eluting stents was assessed by OCT 5-7months after stent implantation. Different subsets of EPC (CD34(+)KDR(+), CD34(+)KDR(+)CD45(dim), CD133(+), CD3(+)CD31(+)), CEC (CD31(+)CD45(-)CD146(+)), and CD31(+)CD45(-)CD146(-) representing large platelets were analysed by flow cytometry, including viability analyses with 7-AAD. Statistical analysis comprised univariate regression analysis and multivariable models integrating OCT and flow cytometry data as well as clinical variables. RESULTS: SSC and frequency of different cell types were highly comparable with previously published data. EPC defined in part by KDR expression were mostly non-viable. On univariate and in multivariable models, no association between EPC counts and strut coverage was detected. For CD31(+)CD45(-)CD146(-) counts, representing large platelets, an inverse relationship with strut coverage was identified by a multivariable regression model adjusting for age, sex, diabetes mellitus, NYHA and CCS class, CRP, serum triglycerides, glucose and creatinine (beta=-9.42, p=0.006). CONCLUSIONS: There was no significant association between EPC or CEC and healing after drug-eluting stent implantation. Yet, CD31(+)CD45(-)CD146(-) cells were associated with low SSC. These data suggest that large platelets may represent a more important mediator of late stent endothelialisation than EPC.
Authors: Santiago Roura; Carolina Gálvez-Montón; Marco A Fernández; Josep Lupón; Antoni Bayes-Genis Journal: J Cardiovasc Transl Res Date: 2016-01-06 Impact factor: 4.132