CD44-v6 Expression in Smooth Muscle Cells in the Postnatal Remodeling Process of Ductus Arteriosus

Published:February 17, 2006DOI:
      Closure of the ductus arteriosus (DA) is due to functional constriction followed by wall remodeling, with neointimal formation caused by proliferation and migration of smooth muscle cells (SMCs) from the media to subendothelium. CD44 is a surface cell proteoglycan family. Its isoform, CD44-v6, is only minimally expressed in SMCs in the media of normal arteries, but is highly expressed in SMCs in the intima and media of injured arteries (e.g., atherosclerosis). Twenty-two autopsy DA specimens, 11 from full-term babies (age range 2 days to 5 months) and 11 from premature babies (age range 3 days to 5 months), with varying degrees of ductal wall remodeling, were evaluated by immunohistochemistry using antiactin, antifibronectin-extradomain A, anti-leukocyte common antigen, anti-CD44, and anti-CD44-v6. In DA with wall remodeling, synthetic antifibronectin-extradomain A–positive SMCs were evident at the neointimal mounds, and the SMCs were highly positive for the CD44-v6 isoform, irrespective of gestational age at birth. Conversely, SMCs of either closed DAs or persistently patent DAs were CD44-v6 negative. In conclusion, the present data provide evidence that closure of DA involves synthetic SMCs highly positive for CD44-v6, and patent or closed DAs are populated by CD44-v6–negative SMCs.
      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 to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Jain M.
        • He Q.
        • Lee W.S.
        • Kashiki S.
        • Foster L.C.
        • Tsai J.C.
        • Lee M.E.
        • Haber E.
        Role of CD44 in the reaction of vascular smooth muscle cells to arterial wall injury.
        J Clin Invest. 1996; 97: 596-603
        • Günthert U.
        in: Dunon D. Mackay C.R. Imhof B.A. Adhesion in Leukocyte Homing and Differentiation. Springer-Verlag, New York1993: 47-63
        • Lazaar A.L.
        • Albelda S.M.
        • Pilewski J.M.
        • Brennan B.
        • Pure E.
        • Panettieri Jr, R.A.
        T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis.
        J Exp Med. 1994; 180: 807-816
        • Shi C.
        • Russell M.E.
        • Bianchi C.
        • Newell J.B.
        • Haber E.
        Murine model of accelerated transplant arteriosclerosis.
        Circ Res. 1994; 75: 199-207
        • Clyman R.I.
        • Chan C.Y.
        • Mauray F.
        • Chen Y.Q.
        • Cox W.
        • Seidner S.R.
        • Lord E.M.
        • Weiss H.
        • Waleh N.
        • Evans S.M.
        • Koch C.J.
        Permanent anatomic closure of the ductus arteriosus in newborn baboons.
        Pediatr Res. 1999; 45: 19-29
        • Svee K.
        • White J.
        • Vaillant P.
        • Jessurun J.
        • Roongta U.
        • Krumwiede M.
        • Johnson D.
        • Henke C.
        Acute lung injury fibroblast migration and invasion of a fibrin matrix is mediated by CD44.
        J Clin Invest. 1996; 98: 1713-1727
        • Newby A.C.
        • Zaltsman A.B.
        Molecular mechanisms in intimal hyperplasia.
        J Pathol. 2000; 190: 300-309
        • Zwolak R.M.
        • Adams M.C.
        • Clowes A.W.
        Kinetics of vein graft hyperplasia.
        J Vasc Surg. 1987; 5: 126-136
        • Schwartz S.M.
        • Heimark R.L.
        • Majesky M.W.
        Developmental mechanisms underlying pathology of arteries.
        Physiol Rev. 1990; 70: 1177-1209
        • Clowes A.W.
        • Reidy M.A.
        • Clowes M.M.
        Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium.
        Lab Invest. 1983; 49: 327-333
        • Raines E.W.
        • Ross R.
        Smooth muscle cells and the pathogenesis of the lesions of atherosclerosis.
        Br Heart J. 1993; 69: S30-S37
        • Waleh N.
        • Seidner S.
        • McCurnin D.
        • Yoder B.
        • Liu B.M.
        • Roman C.
        • Mauray F.
        • Clyman R.I.
        The role of monocyte-derived cells and inflammation in baboon ductus arteriosus remodeling.
        Pediatr Res. 2005; 57: 254-262
        • Slomp J.
        • Gittenberger-de Groot A.C.
        • Glukhova M.A.
        • Conny van Munsteren J.
        • Kockx M.M.
        • Schwartz S.M.
        • Koteliansky V.E.
        Differentiation, dedifferentiation, and apoptosis of smooth muscle cells during the development of the human ductus arteriosus.
        Arterioscler Thromb Vasc Biol. 1997; 17: 1003-1009
        • Travis J.A.
        • Hughes M.G.
        • Wong J.M.
        • Wagner W.D.
        • Geary R.L.
        Hyaluronan enhances contraction of collagen by smooth muscle cells and adventitial fibroblasts.
        Circ Res. 2001; 88: 77-83