Characterization of smooth muscle-like cells in circulating human peripheral blood


      Smooth muscle cells play an important role in human vascular diseases. Several lines of evidence demonstrate that circulating smooth muscle precursor cells contribute to intimal hyperplasia in animal models. We obtained large spindle cells expressing alpha-smooth muscle actin (α-SMA), denoted here as “smooth muscle-like cells” (SMLC), from human peripheral blood mononuclear cells (PBMC). SMLC derived from human PBMC proliferated readily and expressed pro-inflammatory genes during early culture. After long-term culture, SMLC could contract and express characteristic smooth muscle cell markers. We found peripheral blood mononuclear cell expressing α-smooth muscle actin in the circulating blood that bore CD14 and CD105. Sorted CD14/CD105 double-positive PBMC could differentiate into SMLC. The number of CD14–CD105-bearing PBMC increased significantly in patients with coronary artery disease compared to patients without coronary artery disease. These results support the novel concept that smooth muscle precursor cells exist in circulating human blood and may contribute to the pathogenesis of vascular diseases.


      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 Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Libby P.
        Inflammation in atherosclerosis.
        Nature. 2002; 420: 868-874
        • Libby P.
        The molecular bases of the acute coronary syndromes.
        Circulation. 1995; 91: 2844-2850
        • Stary H.C.
        • Chandler A.B.
        • Dinsmore R.E.
        • et al.
        A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the committee on vascular lesions of the council on arteriosclerosis, American Heart Association.
        Circulation. 1995; 92: 1355-1374
        • Ross R.
        • Glomset J.A.
        • Atherosclerosis
        The arterial smooth muscle cells.
        Science. 1973; 180: 1332-1339
        • Lafont A.
        • Libby P.
        The smooth muscle cell: sinner or saint in restenosis and the acute coronary syndromes?.
        J Am Coll Cardiol. 1998; 32: 283-285
        • Ross R.
        The pathogenesis of atherosclerosis—an update.
        New Engl J Med. 1986; 314: 488-500
        • Schwartz S.M.
        • deBlois D.
        • O’Brien E.R.
        The intima. Soil for atherosclerosis and restenosis.
        Circ Res. 1995; 77: 445-465
        • Shanahan C.M.
        • Weissberg P.L.
        Smooth muscle cell heterogeneity: patterns of gene expression in vascular smooth muscle cells in vitro and in vivo.
        Arterioscler Thromb Vasc Biol. 1998; 18: 333-338
        • Han C.I.
        • Campbell G.R.
        • Campbell J.H.
        Circulating bone marrow cells can contribute to neointimal formation.
        J Vasc Res. 2001; 38: 113-119
        • Shimizu K.
        • Sugiyama S.
        • Aikawa M.
        • et al.
        Host bone-marrow cells are a source of donor intimal smooth-muscle-like cells in murine aortic transplant arteriopathy.
        Nat Med. 2001; 7: 738-741
        • Sata M.
        • Saiura A.
        • Kunisato A.
        • et al.
        Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis.
        Nat Med. 2002; 8: 403-409
        • Quaini F.
        • Urbanek K.
        • Beltrami A.P.
        • et al.
        Chimerism of the transplanted heart.
        N Engl J Med. 2002; 346: 5-15
        • Caplice N.M.
        • Bunch T.J.
        • Stalboerger P.G.
        • et al.
        Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation.
        Proc Natl Acad Sci USA. 2003; 100: 4754-4759
        • Sugiyama S.
        • Okada Y.
        • Sukhova G.K.
        • et al.
        Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes.
        Am J Pathol. 2001; 158: 879-891
        • Skalli O.
        • Ropraz P.
        • Trzeciak A.
        • et al.
        A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation.
        J Cell Biol. 1986; 103: 2787-2796
        • Aikawa M.
        • Sivam P.N.
        • Kuro-o M.
        • et al.
        Human smooth muscle myosin heavy chain isoforms as molecular markers for vascular development and atherosclerosis.
        Circ Res. 1993; 73: 1000-1012
        • Ross R.
        • Kariya B.
        Morphogenesis of vascular smooth muscle in atherosclerosis and cell structure.
        in: Bohr D.F. Somlyo A.P. Sparks H.Y. Handbook of physiology: the cardiovascular system, Section 2. American Physiological Society, Bethesda1980: 66-91
        • Owens G.K.
        Regulation of differentiation of vascular smooth muscle cells.
        Physiol Rev. 1995; 75: 487-517
        • Sibinga N.E.
        • Foster L.C.
        • Hsieh C.M.
        • et al.
        Collagen VIII is expressed by vascular smooth muscle cells in response to vascular injury.
        Circ Res. 1997; 80: 532-541
        • Aikawa M.
        • Sakomura Y.
        • Ueda M.
        • et al.
        Redifferentiation of smooth muscle cells after coronary angioplasty determined via myosin heavy chain expression.
        Circulation. 1997; 96: 82-90
        • Mallat Z.
        • Corbaz A.
        • Scoazec A.
        • et al.
        Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability.
        Circulation. 2001; 104: 1598-1603
        • Gerdes N.
        • Sukhova G.K.
        • Libby P.
        • et al.
        Expression of interleukin (IL)-18 and functional IL-18 receptor on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for atherogenesis.
        J Exp Med. 2002; 195: 245-257
        • Sorescu D.
        • Weiss D.
        • Lassegue B.
        • et al.
        Superoxide production and expression of nox family proteins in human atherosclerosis.
        Circulation. 2002; 105: 1429-1435
        • Ravalli S.
        • Albala A.
        • Ming M.
        • et al.
        Inducible nitric oxide synthase expression in smooth muscle cells and macrophages of human transplant coronary artery disease.
        Circulation. 1998; 97: 2338-2345
        • Kalinina N.
        • Agrotis A.
        • Tararak E.
        • et al.
        Cytochrome b558-dependent NAD(P)H oxidase-phox units in smooth muscle and macrophages of atherosclerotic lesions.
        Arterioscler Thromb Vasc Biol. 2002; 22: 2037-2043
        • Campbell G.R.
        • Ryan G.B.
        Origin of myofibroblasts in the avascular capsule around free-floating intraperitoneal blood clots.
        Pathology. 1983; 15: 253-264
        • Bucala R.
        • Spiegel L.A.
        • Chesney J.
        • et al.
        Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair.
        Mol Med. 1994; 1: 71-81
        • Chapuis F.
        • Rosenzwajg M.
        • Yagello M.
        • et al.
        Differentiation of human dendritic cells from monocytes in vitro.
        Eur J Immunol. 1997; 27: 431-441
        • Fernandez Pujol B.
        • Lucibello F.C.
        • Gehling U.M.
        • et al.
        Endothelial-like cells derived from human CD14 positive monocytes.
        Differentiation. 2000; 65: 287-300
        • Yang L.
        • Scott P.G.
        • Giuffre J.
        • et al.
        Peripheral blood fibrocytes from burn patients: identification and quantification of fibrocytes in adherent cells cultured from peripheral blood mononuclear cells.
        Lab Invest. 2002; 82: 1183-1192
        • Conley B.A.
        • Smith J.D.
        • Guerrero-Esteo M.
        • et al.
        Endoglin, a TGF-beta receptor-associated protein, is expressed by smooth muscle cells in human atherosclerotic plaques.
        Atherosclerosis. 2000; 153: 323-335
        • Li D.Y.
        • Sorensen L.K.
        • Brooke B.S.
        • et al.
        Defective angiogenesis in mice lacking endoglin.
        Science. 1999; 284: 1534-1537
        • Barry F.P.
        • Boynton R.E.
        • Haynesworth S.
        • et al.
        The monoclonal antibody SH-2, raised against human mesenchymal stem cells, recognizes an epitope on endoglin (CD105).
        Biochem Biophys Res Commun. 1999; 265: 134-139
        • Zvaifler N.J.
        • Marinova-Mutafchieva L.
        • Adams G.
        • et al.
        Mesenchymal precursor cells in the blood of normal individuals.
        Arthritis Res. 2000; 2: 477-488
        • Simper D.
        • Stalboerger P.G.
        • Panetta C.J.
        • et al.
        Smooth muscle progenitor cells in human blood.
        Circulation. 2002; 106: 1199-1204