Advertisement
Mayo Clinic Proceedings Home

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

      Abstract

      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)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Nkomo V.T.
        • Gardin J.M.
        • Skelton T.N.
        • Gottdiener J.S.
        • Scott C.G.
        • Enriquez-Sarano M.
        Burden of valvular heart diseases: a population-based study.
        Lancet. 2006; 368: 1005-1011
        • Yutzey K.E.
        • Demer L.L.
        • Body S.C.
        • et al.
        Calcific aortic valve disease: a consensus summary from the alliance of investigators on calcific aortic valve disease.
        Arterioscler Thromb Vasc Biol. 2014; 34: 2387-2393
        • Rajamannan N.M.
        • Evans F.J.
        • Aikawa E.
        • et al.
        Calcific aortic valve disease: not simply a degenerative process: a review and agenda for research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group: executive summary: calcific aortic valve disease-2011 update.
        Circulation. 2011; 124: 1783-1791
        • Liu A.C.
        • Joag V.R.
        • Gotlieb A.I.
        The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology.
        Am J Pathol. 2007; 171: 1407-1418
        • Leopold J.A.
        Cellular mechanisms of aortic valve calcification.
        Circ Cardiovasc Interv. 2012; 5: 605-614
        • Kaden J.J.
        • Dempfle C.E.
        • Grobholz R.
        • et al.
        Inflammatory regulation of extracellular matrix remodeling in calcific aortic valve stenosis.
        Cardiovasc Pathol. 2005; 14: 80-87
        • Chalajour F.
        • Treede H.
        • Gehling U.M.
        • et al.
        Identification and characterization of cells with high angiogenic potential and transitional phenotype in calcific aortic valve.
        Exp Cell Res. 2007; 313: 2326-2335
        • Gossl M.
        • Khosla S.
        • Zhang X.
        • et al.
        Role of circulating osteogenic progenitor cells in calcific aortic stenosis.
        J Am Coll Cardiol. 2012; 60: 1945-1953
        • Flammer A.J.
        • Gossl M.
        • Widmer R.J.
        • et al.
        Osteocalcin positive cd133+/cd34-/kdr+ progenitor cells as an independent marker for unstable atherosclerosis.
        Eur Heart J. 2012; 33: 2963-2969
        • Gossl M.
        • Modder U.I.
        • Gulati R.
        • et al.
        Coronary endothelial dysfunction in humans is associated with coronary retention of osteogenic endothelial progenitor cells.
        Eur Heart J. 2010; 31: 2909-2914
        • Hristov M.
        • Erl W.
        • Weber P.C.
        Endothelial progenitor cells: mobilization, differentiation, and homing.
        Arterioscler Thromb Vasc Biol. 2003; 23: 1185-1189
        • Yin A.H.
        • Miraglia S.
        • Zanjani E.D.
        • et al.
        AC133, a novel marker for human hematopoietic stem and progenitor cells.
        Blood. 1997; 90: 5002-5012
        • Quirici N.
        • Soligo D.
        • Caneva L.
        • Servida F.
        • Bossolasco P.
        • Deliliers G.L.
        Differentiation and expansion of endothelial cells from human bone marrow CD133+ cells.
        Br J Haematol. 2001; 115: 186-194
        • Nishimura R.A.
        • Otto C.M.
        • Bonow R.O.
        • et al.
        2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2014; 63: e57-e185
        • Gössl M.
        • Mödder U.
        • Atkinson E.
        • Lerman A.
        • Khosla S.
        Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.
        J Am Coll Cardiol. 2008; 52: 1314-1325
        • Collin J.
        • Gössl M.
        • Matsuo Y.
        • et al.
        Osteogenic monocytes within the coronary circulation and their association with plaque vulnerability in patients with early atherosclerosis.
        Int J Cardiol. 2015; 181: 57-64
        • Nagy E.
        • Eriksson P.
        • Yousry M.
        • et al.
        Valvular osteoclasts in calcification and aortic valve stenosis severity.
        Int J Cardiol. 2013; 168: 2264-2271
        • Yousry M.
        • Rickenlund A.
        • Petrini J.
        • et al.
        Real-time imaging required for optimal echocardiographic assessment of aortic valve calcification.
        Clin Physiol Funct Imaging. 2012; 32: 470-475
        • Rajamannan N.M.
        • Subramaniam M.
        • Rickard D.
        • et al.
        Human aortic valve calcification is associated with an osteoblast phenotype.
        Circulation. 2003; 107: 2181-2184
        • Mohler III, E.R.
        • Gannon F.
        • Reynolds C.
        • Zimmerman R.
        • Keane M.G.
        • Kaplan F.S.
        Bone formation and inflammation in cardiac valves.
        Circulation. 2001; 103: 1522-1528
        • Mazzone A.
        • Epistolato M.C.
        • De Caterina R.
        • et al.
        Neoangiogenesis, T-lymphocyte infiltration, and heat shock protein-60 are biological hallmarks of an immunomediated inflammatory process in end-stage calcified aortic valve stenosis.
        J Am Coll Cardiol. 2004; 43: 1670-1676
        • Matsumoto Y.
        • Adams V.
        • Walther C.
        • et al.
        Reduced number and function of endothelial progenitor cells in patients with aortic valve stenosis: a novel concept for valvular endothelial cell repair.
        Eur Heart J. 2009; 30: 346-355