Role of circulating osteogenic progenitor cells in calcific aortic stenosis

Mario Gössl, Sundeep Khosla, Xin Zhang, Nara Higano, Kyra L. Jordan, Darrell Loeffler, Maurice E Sarano, Ryan J. Lennon, Lilach O Lerman, Amir Lerman

Research output: Contribution to journalArticle

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Abstract

Objectives: The purpose of this study was to determine the role of circulating endothelial progenitor cells with osteoblastic phenotype (EPC-OCN) in human aortic valve calcification (AVC). Background: Recent evidence suggests that rather than passive mineralization, AVC is an active atherosclerotic process with an osteoblastic component resembling coronary calcification. We have recently identified circulating EPCs with osteogenic properties carrying both endothelial progenitor (CD34, KDR) and osteoblastic (osteocalcin [OCN]) cell surface markers. Methods: Blood samples from controls (n = 22) and patients with mild to moderate calcific aortic stenosis (mi-moAS, n = 17), severe calcific AS (sAS, n = 26), and both sAS and severe coronary artery disease (sCAD) (n = 33) were collected during diagnostic coronary angiography. By using flow cytometry, peripheral blood mononuclear cells were analyzed for CD34, KDR, and OCN. Resected normal and calcified aortic valves were analyzed histologically. Results: Patients with mi-moAS and patients with sAS/sCAD had significantly less EPCs (CD34+/KDR+/OCN-) than controls. Patients with sAS showed significantly higher numbers of EPC-OCN (CD34+/KDR+/OCN+) than controls. In addition, the percentage of EPC costaining for OCN was higher in all disease groups compared with controls. A subgroup analysis of younger patients with bicuspid sAS showed a similar pattern of significantly lower EPCs but a high percentage of coexpression of OCN. Immunofluorescence showed colocalization of nuclear factor kappa-B and OCN in diseased and normal valves. CD34+/OCN+ cells were abundant in the endothelial and deeper cell layers of calcific aortic valve tissue but not in normal aortic valve tissue. Conclusions: Circulating EPC-OCN may play a significant role in the pathogenesis and as markers of prognostication of calcific AS.

Original languageEnglish (US)
Pages (from-to)1945-1953
Number of pages9
JournalJournal of the American College of Cardiology
Volume60
Issue number19
DOIs
StatePublished - Nov 6 2012

Fingerprint

Osteocalcin
Stem Cells
Aortic Valve
Phenotype
Coronary Artery Disease
Calcification of Aortic Valve
NF-kappa B
Bicuspid
Coronary Angiography
Fluorescent Antibody Technique
Blood Cells
Flow Cytometry
Endothelial Cells
erucylphosphocholine

Keywords

  • bicuspid aortic valve disease
  • calcific aortic valve stenosis
  • endothelial progenitor cells
  • osteocalcin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Role of circulating osteogenic progenitor cells in calcific aortic stenosis. / Gössl, Mario; Khosla, Sundeep; Zhang, Xin; Higano, Nara; Jordan, Kyra L.; Loeffler, Darrell; Sarano, Maurice E; Lennon, Ryan J.; Lerman, Lilach O; Lerman, Amir.

In: Journal of the American College of Cardiology, Vol. 60, No. 19, 06.11.2012, p. 1945-1953.

Research output: Contribution to journalArticle

Gössl, Mario ; Khosla, Sundeep ; Zhang, Xin ; Higano, Nara ; Jordan, Kyra L. ; Loeffler, Darrell ; Sarano, Maurice E ; Lennon, Ryan J. ; Lerman, Lilach O ; Lerman, Amir. / Role of circulating osteogenic progenitor cells in calcific aortic stenosis. In: Journal of the American College of Cardiology. 2012 ; Vol. 60, No. 19. pp. 1945-1953.
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AU - Gössl, Mario

AU - Khosla, Sundeep

AU - Zhang, Xin

AU - Higano, Nara

AU - Jordan, Kyra L.

AU - Loeffler, Darrell

AU - Sarano, Maurice E

AU - Lennon, Ryan J.

AU - Lerman, Lilach O

AU - Lerman, Amir

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KW - bicuspid aortic valve disease

KW - calcific aortic valve stenosis

KW - endothelial progenitor cells

KW - osteocalcin

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