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Circulating Osteogenic Progenitor Cells in Mild, Moderate, and Severe Aortic Valve Stenosis


      The aim of this study was to characterize endothelial progenitor cells with osteoblastic phenotype (EPC-OCNs) and their role in individuals with varying degrees of aortic stenosis (AS). Peripheral blood mononuclear cells retrieved from blood samples of individuals with mild (n=40), moderate (n=35), or severe (n=103) AS from September 16, 2008, through March 30, 2015, were analyzed by flow cytometry for the EPC surface markers CD34, CD133, and kinase insert domain receptor (KDR) and the osteoblastic cell surface marker OCN. Levels of EPC-OCNs were correlated with AS severity and calcifications. Patients with severe AS had significantly elevated numbers of total circulating EPC-OCNs, including the EPC-OCN subtypes CD133+/OCN+, CD34+/CD133+/OCN+, and CD133+/KDR+/OCN+, compared with those with mild AS. Individuals with moderate AS also had significantly increased numbers of the circulating progenitor cell CD133+/OCN+ compared with patients with mild AS. There was a significant association between total circulating EPC-OCN levels and aortic valve (AV) calcification, AV mean gradient, and AV area measured by echocardiography. In summary, this study found the presence of circulating EPC-OCNs in patients with progressive AV stenosis. These findings might support the potential role for EPC-OCNs in the progression of AV stenosis and calcification.

      Abbreviations and Acronyms:

      AS (aortic stenosis), AV (aortic valve), AVC (aortic valve calcification), CAD (coronary artery disease), EPC (endothelial progenitor cell), EPC-OCN (endothelial progenitor cell with osteoblastic phenotype), KDR (kinase insert domain receptor), TVI (time-velocity integral), VEGF (vascular endothelial growth factor), VIC (valvular interstitial cells)
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