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Musashi-1 expression in atherosclerotic arteries and its relevance to the origin of arterial smooth muscle cells: Histopathological findings and speculations

  • Yuri V. Bobryshev
    Correspondence
    Corresponding author at: Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia. Tel.: +61 2 9385 1217; fax: +61 2 9385 1217.
    Affiliations
    Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia

    St. Vincent's Centre for Applied Medical Research and Department of Surgery, St Vincent's Hospital, University of New South Wales, Sydney, Australia
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  • Dinh Tran
    Affiliations
    Division of Anatomical Pathology, St. Vincent's Hospital, Sydney, Australia
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  • Natalia K. Botelho
    Affiliations
    St. Vincent's Centre for Applied Medical Research and Department of Surgery, St Vincent's Hospital, University of New South Wales, Sydney, Australia
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  • Reginald V.N. Lord
    Affiliations
    St. Vincent's Centre for Applied Medical Research and Department of Surgery, St Vincent's Hospital, University of New South Wales, Sydney, Australia
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  • Alexander N. Orekhov
    Affiliations
    Institute for Atherosclerosis Research, Russian Academy of Natural Sciences, Moscow, Russia

    Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia
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      Abstract

      The origin of smooth muscle cells in developing atherosclerotic lesions is a controversial topic with accumulating evidence indicating that at least some arterial smooth muscle cells might originate from bone marrow-derived smooth muscle cell precursors circulating in the blood. The stem cell markers currently used for the identification of stem cells in the arterial intima can be expressed by a number of different cell types residing in the arterial wall, such as mast cells, endothelial cells and dendritic cells, which can make interpretation of the data obtained somewhat ambiguous. In the present study we examined whether the putative intestinal stem cell marker Musashi-1 is expressed in the arterial wall. Using a multiplexed tandem polymerase chain reaction method (MT-PCR) and immunohistochemistry, Musashi-1 expression was revealed in human coronary arterial wall tissue segments, and this finding was followed by the demonstration of significantly higher expression levels of Musashi-1 in atherosclerotic plaques compared with those in undiseased intimal sites. Double immunohistochemistry demonstrated that in the arterial wall Musashi-1 positive cells either did not display any specific markers of cells that are known to reside in the arterial intima or Musashi-1 was co-expressed by smooth muscle α-actin positive cells. Some Musashi-1 positive cells were found along the luminal surface of arteries as well as within microvessels formed in atherosclerotic plaques by neovascularization, which supports the possibility that Musashi-1 positive cells might intrude into the arterial wall from the blood and might even represent circulating smooth muscle cell precursors.

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      References

        • Ross R.
        Atherosclerosis—an inflammatory disease.
        N Engl J Med. 1999; 340: 115-126
        • Hansson G.K.
        Atherosclerosis—an immune disease: The Anitschkov Lecture 2007.
        Atherosclerosis. 2009; 202: 2-10
        • Vanderlaan P.A.
        • Reardon C.A.
        The unusual suspects: an overview of the minor leukocyte populations in atherosclerosis.
        J Lipid Res. 2005; 46: 829-838
        • Galkina E.
        • Ley K.
        Leukocyte influx in atherosclerosis.
        Curr Drug Targets. 2007; 8: 1239-1248
        • Weber C.
        • Zernecke A.
        • Libby P.
        The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models.
        Nat Rev Immunol. 2008; 8: 802-815
        • Bobryshev Y.V.
        Dendritic cells and their role in atherogenesis.
        Lab Invest. 2010; 90: 970-984
        • McNeill E.
        • Channon K.M.
        • Greaves D.R.
        Inflammatory cell recruitment in cardiovascular disease: murine models and potential clinical applications.
        Clin Sci (Lond). 2010; 118: 641-655
        • 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
        • Kashiwakura Y.
        • Katoh Y.
        • Tamayose K.
        • et al.
        Isolation of bone marrow stromal cell-derived smooth muscle cells by a human SM22alpha promoter: in vitro differentiation of putative smooth muscle progenitor cells of bone marrow.
        Circulation. 2003; 107: 2078-2081
        • Hillebrands J.L.
        • Klatter F.A.
        • Rozing J.
        Origin of vascular smooth muscle cells and the role of circulating stem cells in transplant arteriosclerosis.
        Arterioscler Thromb Vasc Biol. 2003; 23: 380-387
        • Liu C.
        • Nath K.A.
        • Katusic Z.S.
        • Caplice N.M.
        Smooth muscle progenitor cells in vascular disease.
        Trends Cardiovasc Med. 2004; 14: 288-293
        • Sata M.
        Role of circulating vascular progenitors in angiogenesis, vascular healing, and pulmonary hypertension: lessons from animal models.
        Arterioscler Thromb Vasc Biol. 2006; 26: 1008-1014
        • Xiao Q.
        • Kiechl S.
        • Patel S.
        • et al.
        Endothelial progenitor cells, cardiovascular risk factors, cytokine levels and atherosclerosis-results from a large population-based study.
        PLoS One. 2007; 2: e975
        • Hristov M.
        • Zernecke A.
        • Schober A.
        • Weber C.
        Adult progenitor cells in vascular remodeling during atherosclerosis.
        Biol Chem. 2008; 389: 837-844
        • Hristov M.
        • Weber C.
        Ambivalence of progenitor cells in vascular repair and plaque stability.
        Curr Opin Lipidol. 2008; 19: 491-497
        • Liu C.
        • Wang S.
        • Metharom P.
        • Caplice N.M.
        Myeloid lineage of human endothelial outgrowth cells circulating in blood and vasculogenic endothelial-like cells in the diseased vessel wall.
        J Vasc Res. 2009; 46: 581-591
        • Hao H.
        • Gabbiani G.
        • Bochaton-Piallat M.L.
        Arterial smooth muscle cell heterogeneity: implications for atherosclerosis and restenosis development.
        Arterioscler Thromb Vasc Biol. 2003; 23: 1510-1520
        • Hristov M.
        • Weber C.
        Progenitor cell trafficking in the vascular wall.
        J Thromb Haemost. 2009; 7: 31-34
        • Simper D.
        • Stalboerger P.G.
        • Panetta C.J.
        • Wang S.
        • Caplice N.M.
        Smooth muscle progenitor cells in human blood.
        Circulation. 2002; 106: 1199-1204
        • Zoll J.
        • Fontaine V.
        • Gourdy P.
        • et al.
        Role of human smooth muscle cell progenitors in atherosclerotic plaque development and composition.
        Cardiovasc Res. 2008; 77: 471-480
        • Metharom P.
        • Liu C.
        • Wang S.
        • et al.
        Myeloid lineage of high proliferative potential human smooth muscle outgrowth cells circulating in blood and vasculogenic smooth muscle-like cells in vivo.
        Atherosclerosis. 2008; 198: 29-38
        • Tillmanns J.
        • Rota M.
        • Hosoda T.
        • et al.
        Formation of large coronary arteries by cardiac progenitor cells.
        Proc Natl Acad Sci USA. 2008; 105: 1668-1673
        • Metharom P.
        • Kumar A.H.
        • Weiss S.
        • Caplice N.M.
        A specific subset of mouse bone marrow cells has smooth muscle cell differentiation capacity-brief report.
        Arterioscler Thromb Vasc Biol. 2010; 30: 533-535
        • Metharom P.
        • Caplice N.M.
        Vascular disease: a new progenitor biology.
        Curr Vasc Pharmacol. 2007; 5: 61-68
        • Iwata H.
        • Sata M.
        Potential contribution of bone marrow-derived precursors to vascular repair and lesion formation: lessons from animal models of vascular diseases.
        Front Biosci. 2007; 12: 4157-4167
        • Tanaka K.
        • Sata M.
        Contribution of circulating vascular progenitors in lesion formation and vascular healing: lessons from animal models.
        Curr Opin Lipidol. 2008; 19: 498-504
        • Iwata H.
        • Sata M.
        Origin of cells that contribute to neointima growth.
        Circulation. 2008; 117: 3060-3061
        • Tanaka K.
        • Sata M.
        Role of vascular progenitor cells in cardiovascular disease.
        Curr Pharm Des. 2009; 15: 2760-2768
        • van Oostrom O.
        • Fledderus J.O.
        • de Kleijn D.
        • Pasterkamp G.
        • Verhaar M.C.
        Smooth muscle progenitor cells: friend or foe in vascular disease?.
        Curr Stem Cell Res Ther. 2009; 4: 131-140
        • Sirker A.A.
        • Astroulakis Z.M.
        • Hill J.M.
        Vascular progenitor cells and translational research: the role of endothelial and smooth muscle progenitor cells in endogenous arterial remodelling in the adult.
        Clin Sci (Lond). 2009; 116: 283-299
        • Hu Y.
        • Davison F.
        • Ludewig B.
        • et al.
        Smooth muscle cells in transplant atherosclerotic lesions are originated from recipients, but not bone marrow progenitor cells.
        Circulation. 2002; 106: 1834-1839
        • Bentzon J.F.
        • Weile C.
        • Sondergaard C.S.
        • et al.
        Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in ApoE knockout mice.
        Arterioscler Thromb Vasc Biol. 2006; 26: 2696-2702
        • Bentzon J.F.
        • Sondergaard C.S.
        • Kassem M.
        • Falk E.
        Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice.
        Circulation. 2007; 116: 2053-2061
        • Bentzon J.F.
        • Falk E.
        Circulating smooth muscle progenitor cells in atherosclerosis and plaque rupture: current perspective and methods of analysis.
        Vascul Pharmacol. 2010; 52: 11-20
        • Bachelet I.
        • Levi-Schaffer F.
        Mast cells as effector cells: a co-stimulating question.
        Trends Immunol. 2007; 28: 360-365
        • Le Bras A.
        • Vijayaraj P.
        • Oettgen P
        Molecular mechanisms of endothelial differentiation.
        Vasc Med. 2010; (Epub ahead of print: PMID: 20621955)
        • Auffray C.
        • Sieweke M.H.
        • Geissmann F.
        Blood monocytes: development, heterogeneity, and relationship with dendritic cells.
        Annu Rev Immunol. 2009; 27: 669-692
        • Okano H.
        • Kawahara H.
        • Toriya M.
        • et al.
        Function of RNA-binding protein Musashi-1 in stem cells.
        Exp Cell Res. 2005; 306: 349-356
        • Potten C.S.
        • Booth C.
        • Tudor G.L.
        • et al.
        Identification of a putative intestinal stem cell and early lineage marker: Musashi-1.
        Differentiation. 2003; 7: 128-141
        • Montgomery R.K.
        • Breault D.T.
        Small intestinal stem cell markers.
        J Anat. 2008; 213: 52-58
        • Yen T.H.
        • Wright N.A.
        The gastrointestinal tract stem cell niche.
        Stem Cell Rev. 2006; 2: 203-212
        • Schulenburg A.
        • Cech P.
        • Herbacek I.
        • et al.
        CD44-positive colorectal adenoma cells express the potential stem cell markers musashi antigen (msi1) and ephrin B2 receptor (EphB2).
        J Pathol. 2007; 213: 152-160
        • Fan L.F.
        • Dong W.G.
        • Jiang C.Q.
        • et al.
        Expression of putative stem cell genes Musashi-1 and beta1-integrin in human colorectal adenomas and adenocarcinomas.
        Int J Colorectal Dis. 2010; 25: 17-23
        • Bobryshev Y.V.
        • Freeman A.K.
        • Botelho N.K.
        • et al.
        Expression of the putative stem cell marker Musashi-1 in Barrett's esophagus and esophageal adenocarcinoma.
        Dis Esophagus. 2010; 23: 580-589
        • Götte M.
        • Wolf M.
        • Staebler A.
        • et al.
        Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma.
        J Pathol. 2008; 215: 317-329
        • Moreira A.L.
        • Gonen M.
        • Rekhtman N.
        • Downey R.J.
        Progenitor stem cell marker expression by pulmonary carcinomas.
        Mod Pathol. 2010; 23: 889-895
        • Bobryshev Y.V.
        • Lord R.S.
        Mapping of vascular dendritic cells in atherosclerotic arteries suggests their involvement in local immune-inflammatory reactions.
        Cardiovasc Res. 1998; 37: 799-810
        • Bobryshev Y.V.
        • Cherian S.M.
        • Inder S.J.
        • Lord R.S.
        Neovascular expression of VE-cadherin in human atherosclerotic arteries and its relation to intimal inflammation.
        Cardiovasc Res. 1999; 43: 1003-1017
        • Grant K.
        • Jerome W.G.
        Laser capture microdissection as an aid to ultrastructural analysis.
        Microsc Microanal. 2002; 8: 170-175
        • Bobryshev Y.V.
        Intracellular localization of oxidized low-density lipoproteins in atherosclerotic plaque cells revealed by electron microscopy combined with laser capture microdissection.
        J Histochem Cytochem. 2005; 53: 793-797
        • Keita M.
        • Magy L.
        • Richard L.
        • Piaser M.
        • Vallat J.M.
        LR white post-embedding colloidal gold method to immunostain MBP, P0, NF and S100 in glutaraldehyde-fixed peripheral nerve tissue.
        J Peripher Nerv Syst. 2002; 7: 128-133
        • Simmons S.R.
        • Sims P.A.
        • Albrecht R.M.
        Alpha IIb beta 3 redistribution triggered by receptor cross-linking.
        Arterioscler Thromb Vasc Biol. 1997; 17: 3311-3320
        • Bobryshev Y.V.
        Transdifferentiation of smooth muscle cells into chondrocytes in atherosclerotic arteries in situ: implications for diffuse intimal calcification.
        J Pathol. 2005; 205: 641-650
        • Stanley K.K.
        • Szewczuk E.
        Multiplexed tandem PCR: gene profiling from small amounts of RNA using SYBR Green detection.
        Nucleic Acids Res. 2005; 33: e180
        • Babaev V.R.
        • Bobryshev Y.V.
        • Stenina O.V.
        • Tararak E.M.
        • Gabbiani G.
        Heterogeneity of smooth muscle cells in atheromatous plaque of human aorta.
        Am J Pathol. 1990; 136: 1031-1042
        • Bobryshev Y.V.
        • Killingsworth M.C.
        • Lord R.S.
        • Grabs A.J.
        Matrix vesicles in the fibrous cap of atherosclerotic plaque: possible contribution to plaque rupture.
        J Cell Mol Med. 2008; 12: 2073-2082
        • Bochaton-Piallat M.L.
        • Gabbiani G.
        Modulation of smooth muscle cell proliferation and migration: role of smooth muscle cell heterogeneity.
        Handb Exp Pharmacol. 2005; 170: 645-663
        • Majesky M.W.
        Vascular smooth muscle diversity: insights from developmental biology.
        Curr Atheroscler Rep. 2003; 5: 208-213
        • Owens G.K.
        Molecular control of vascular smooth muscle cell differentiation and phenotypic plasticity.
        Novartis Found Symp. 2007; 283: 174-191
        • McDonald O.G.
        • Owens G.K.
        Programming smooth muscle plasticity with chromatin dynamics.
        Circ Res. 2007; 100: 1428-1441
        • Bobryshev Y.V.
        • Killingsworth M.C.
        • Lord R.S.
        Spatial distribution of osteoblast-specific transcription factor Cbfa1 and bone formation in atherosclerotic arteries.
        Cell Tissue Res. 2008; 333: 225-235
        • Hruska K.A.
        Vascular smooth muscle cells in the pathogenesis of vascular calcification.
        Circ Res. 2009; 104: 710-711
        • Speer M.Y.
        • Yang H.Y.
        • Brabb T.
        • et al.
        Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries.
        Circ Res. 2009; 104: 733-741
        • 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