Osteocalcin positive CD133+/CD34-/KDR+ progenitor cells as an independent marker for unstable atherosclerosis

Andreas J. Flammer, Mario Gössl, Robert Jay Widmer, Martin Reriani, Ryan Lennon, Darrell Loeffler, Sarah Shonyo, Robert D. Simari, Lilach O Lerman, Sundeep Khosla, Amir Lerman

Research output: Contribution to journalArticle

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Abstract

Aims For the characterization of endothelial progenitor cells (EPCs), commonly the markers CD34 and KDR have been used. CD133+/CD34-/KDR+ cells may represent more immature 'early' progenitors. In patients with coronary artery disease (CAD), a large fraction of EPCs carry the osteoblastic marker osteocalcin (OCN), which may mediate vascular calcification and abnormal repair. The aim of this study was to evaluate the expression of OCN+ 'early' EPCs in patients with risk factors (RFs) and a history of stable (history of stenting/coronary artery bypass grafting) or unstable CAD (myocardial infarction). Methods and resultsMedical history and blood samples from 282 patients (age 58 ± 16 years) with CAD or at least one RF (mean 2.5 ± 1.5) were analysed. For the analysis of EPC markers (CD133, CD34, KDR) and OCN, the flow cytometry of peripheral blood mononuclear cells was performed. Circulating OCN+/CD133+/CD34-/KDR+ cells (median counts [interquartile range] per 100 000 events) were 15 [4-41] in patients with RF (n = 199), 26 [1-136] in those with a history of stable (n = 57), and 246 [105-308] in those with a history of unstable CAD (n = 26; P < 0.001). The association with unstable CAD remained highly significant even after multivariate adjusting for RFs and the different characteristics of the groups. Osteocalcin positive 'early' EPCs trend to predict further events [HR for each doubling of the cell number: 1.20 (95% CI: 1.00-1.46), P = 0.06].ConclusionCirculating OCN+ 'early' EPCs are strongly associated with unstable CAD. Therefore, this particular subset of EPCs could mediate abnormal vascular repair and may help identifying patients with a more unstable phenotype of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)2963-2969
Number of pages7
JournalEuropean Heart Journal
Volume33
Issue number23
DOIs
StatePublished - Dec 2012

Fingerprint

Osteocalcin
Atherosclerosis
Stem Cells
Coronary Artery Disease
Cell Count
Vascular Calcification
Endothelial Progenitor Cells
Coronary Artery Bypass
Blood Vessels
Blood Cells
Flow Cytometry
History
Myocardial Infarction
Phenotype

Keywords

  • Arthrosclerosis
  • Coronary artery disease
  • Endothelial progenitor cells
  • Marker
  • Osteocalcin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Osteocalcin positive CD133+/CD34-/KDR+ progenitor cells as an independent marker for unstable atherosclerosis. / Flammer, Andreas J.; Gössl, Mario; Widmer, Robert Jay; Reriani, Martin; Lennon, Ryan; Loeffler, Darrell; Shonyo, Sarah; Simari, Robert D.; Lerman, Lilach O; Khosla, Sundeep; Lerman, Amir.

In: European Heart Journal, Vol. 33, No. 23, 12.2012, p. 2963-2969.

Research output: Contribution to journalArticle

Flammer, AJ, Gössl, M, Widmer, RJ, Reriani, M, Lennon, R, Loeffler, D, Shonyo, S, Simari, RD, Lerman, LO, Khosla, S & Lerman, A 2012, 'Osteocalcin positive CD133+/CD34-/KDR+ progenitor cells as an independent marker for unstable atherosclerosis', European Heart Journal, vol. 33, no. 23, pp. 2963-2969. https://doi.org/10.1093/eurheartj/ehs234
Flammer, Andreas J. ; Gössl, Mario ; Widmer, Robert Jay ; Reriani, Martin ; Lennon, Ryan ; Loeffler, Darrell ; Shonyo, Sarah ; Simari, Robert D. ; Lerman, Lilach O ; Khosla, Sundeep ; Lerman, Amir. / Osteocalcin positive CD133+/CD34-/KDR+ progenitor cells as an independent marker for unstable atherosclerosis. In: European Heart Journal. 2012 ; Vol. 33, No. 23. pp. 2963-2969.
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abstract = "Aims For the characterization of endothelial progenitor cells (EPCs), commonly the markers CD34 and KDR have been used. CD133+/CD34-/KDR+ cells may represent more immature 'early' progenitors. In patients with coronary artery disease (CAD), a large fraction of EPCs carry the osteoblastic marker osteocalcin (OCN), which may mediate vascular calcification and abnormal repair. The aim of this study was to evaluate the expression of OCN+ 'early' EPCs in patients with risk factors (RFs) and a history of stable (history of stenting/coronary artery bypass grafting) or unstable CAD (myocardial infarction). Methods and resultsMedical history and blood samples from 282 patients (age 58 ± 16 years) with CAD or at least one RF (mean 2.5 ± 1.5) were analysed. For the analysis of EPC markers (CD133, CD34, KDR) and OCN, the flow cytometry of peripheral blood mononuclear cells was performed. Circulating OCN+/CD133+/CD34-/KDR+ cells (median counts [interquartile range] per 100 000 events) were 15 [4-41] in patients with RF (n = 199), 26 [1-136] in those with a history of stable (n = 57), and 246 [105-308] in those with a history of unstable CAD (n = 26; P < 0.001). The association with unstable CAD remained highly significant even after multivariate adjusting for RFs and the different characteristics of the groups. Osteocalcin positive 'early' EPCs trend to predict further events [HR for each doubling of the cell number: 1.20 (95{\%} CI: 1.00-1.46), P = 0.06].ConclusionCirculating OCN+ 'early' EPCs are strongly associated with unstable CAD. Therefore, this particular subset of EPCs could mediate abnormal vascular repair and may help identifying patients with a more unstable phenotype of atherosclerosis.",
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AU - Flammer, Andreas J.

AU - Gössl, Mario

AU - Widmer, Robert Jay

AU - Reriani, Martin

AU - Lennon, Ryan

AU - Loeffler, Darrell

AU - Shonyo, Sarah

AU - Simari, Robert D.

AU - Lerman, Lilach O

AU - Khosla, Sundeep

AU - Lerman, Amir

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N2 - Aims For the characterization of endothelial progenitor cells (EPCs), commonly the markers CD34 and KDR have been used. CD133+/CD34-/KDR+ cells may represent more immature 'early' progenitors. In patients with coronary artery disease (CAD), a large fraction of EPCs carry the osteoblastic marker osteocalcin (OCN), which may mediate vascular calcification and abnormal repair. The aim of this study was to evaluate the expression of OCN+ 'early' EPCs in patients with risk factors (RFs) and a history of stable (history of stenting/coronary artery bypass grafting) or unstable CAD (myocardial infarction). Methods and resultsMedical history and blood samples from 282 patients (age 58 ± 16 years) with CAD or at least one RF (mean 2.5 ± 1.5) were analysed. For the analysis of EPC markers (CD133, CD34, KDR) and OCN, the flow cytometry of peripheral blood mononuclear cells was performed. Circulating OCN+/CD133+/CD34-/KDR+ cells (median counts [interquartile range] per 100 000 events) were 15 [4-41] in patients with RF (n = 199), 26 [1-136] in those with a history of stable (n = 57), and 246 [105-308] in those with a history of unstable CAD (n = 26; P < 0.001). The association with unstable CAD remained highly significant even after multivariate adjusting for RFs and the different characteristics of the groups. Osteocalcin positive 'early' EPCs trend to predict further events [HR for each doubling of the cell number: 1.20 (95% CI: 1.00-1.46), P = 0.06].ConclusionCirculating OCN+ 'early' EPCs are strongly associated with unstable CAD. Therefore, this particular subset of EPCs could mediate abnormal vascular repair and may help identifying patients with a more unstable phenotype of atherosclerosis.

AB - Aims For the characterization of endothelial progenitor cells (EPCs), commonly the markers CD34 and KDR have been used. CD133+/CD34-/KDR+ cells may represent more immature 'early' progenitors. In patients with coronary artery disease (CAD), a large fraction of EPCs carry the osteoblastic marker osteocalcin (OCN), which may mediate vascular calcification and abnormal repair. The aim of this study was to evaluate the expression of OCN+ 'early' EPCs in patients with risk factors (RFs) and a history of stable (history of stenting/coronary artery bypass grafting) or unstable CAD (myocardial infarction). Methods and resultsMedical history and blood samples from 282 patients (age 58 ± 16 years) with CAD or at least one RF (mean 2.5 ± 1.5) were analysed. For the analysis of EPC markers (CD133, CD34, KDR) and OCN, the flow cytometry of peripheral blood mononuclear cells was performed. Circulating OCN+/CD133+/CD34-/KDR+ cells (median counts [interquartile range] per 100 000 events) were 15 [4-41] in patients with RF (n = 199), 26 [1-136] in those with a history of stable (n = 57), and 246 [105-308] in those with a history of unstable CAD (n = 26; P < 0.001). The association with unstable CAD remained highly significant even after multivariate adjusting for RFs and the different characteristics of the groups. Osteocalcin positive 'early' EPCs trend to predict further events [HR for each doubling of the cell number: 1.20 (95% CI: 1.00-1.46), P = 0.06].ConclusionCirculating OCN+ 'early' EPCs are strongly associated with unstable CAD. Therefore, this particular subset of EPCs could mediate abnormal vascular repair and may help identifying patients with a more unstable phenotype of atherosclerosis.

KW - Arthrosclerosis

KW - Coronary artery disease

KW - Endothelial progenitor cells

KW - Marker

KW - Osteocalcin

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