Skip to main content
SpringerLink
Log in

Regulation and characteristics of vascular smooth muscle cell phenotypic diversity

  • review article
  • Published:
Netherlands Heart Journal Aims and scope Submit manuscript

Abstract

Vascular smooth muscle cells can perform both contractile and synthetic functions, which are associated with and characterised by changes in morphology, proliferation and migration rates, and the expression of different marker proteins. The resulting phenotypic diversity of smooth muscle cells appears to be a function of innate genetic programmes and environmental cues, which include biochemical factors, extracellular matrix components, and physical factors such as stretch and shear stress. Because of the diversity among smooth muscle cells, blood vessels attain the flexibility that is necessary to perform efficiently under different physiological and pathological conditions. In this review, we discuss recent literature demonstrating the extent and nature of smooth muscle cell diversity in the vascular wall and address the factors that affect smooth muscle cell phenotype. (Neth Heart J 2007;15:100-8.)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 2004;84:767-801.

    Google Scholar 

  • Gittenberger-de Groot AC, DeRuiter MC, Bergwerff M, et al. Smooth muscle cell origin and its relation to heterogeneity in development and disease. Arterioscler Thromb Vasc Biol 1999;19: 1589-94.

    Google Scholar 

  • Hao H, Gabbiani G, Bochaton-Piallat ML. Arterial smooth muscle cell heterogeneity: implications for atherosclerosis and restenosis development. Arterioscler Thromb Vasc Biol 2003;23:1510-0.

    Google Scholar 

  • Chamley-Campbell J, Campbell GR, Ross R. The smooth muscle cell in culture. Physiol Rev 1979;59:1-61.

    Google Scholar 

  • Miano JM. Serum response factor: toggling between disparate programs of gene expression. J Mol Cell Cardiol 2003;35:577-93.

    Google Scholar 

  • Christen T, Bochaton-Piallat ML, Neuville P, et al. Cultured porcine coronary artery smooth muscle cells. A new model with advanced differentiation. Circ Res 1999;85:99-107.

    Google Scholar 

  • Miano JM, Cserjesi P, Ligon KL, et al. Smooth muscle myosin heavy chain exclusively marks the smooth muscle lineage during mouse embryogenesis. Circ Res 1994;75:803-12.

    Google Scholar 

  • Christen T, Verin V, Bochaton-Piallat M, et al. Mechanisms of neointima formation and remodeling in the porcine coronary artery. Circulation 2001;103:882-8.

    Google Scholar 

  • Kuro-o M, Nagai R, Nakahara K, et al. cDNA cloning of a myosin heavy chain isoform in embryonic smooth muscle and its expression during vascular development and in arteriosclerosis. J Biol Chem 1991;266:3768-73.

    Google Scholar 

  • Neuville P, Geinoz A, Benzonana G, et al. Cellular retinol-binding protein-1 is expressed by distinct subsets of rat arterial smooth muscle cells in vitro and in vivo. Am J Pathol 1997;150:509-21.

    Google Scholar 

  • Glukhova MA, Kabakov AE, Frid MG, et al. Modulation of human aorta smooth muscle cell phenotype: a study of muscle-specific variants of vinculin, caldesmon, and actin expression. Proc Natl Acad Sci USA 1988;85:9542-6.

    Google Scholar 

  • Frid MG, Moiseeva EP, Stenmark KR. Multiple phenotypically distinct smooth muscle cell populations exist in the adult and developing bovine pulmonary arterial media in vivo. Circ Res 1994;75:669-81.

    Google Scholar 

  • Regan CP, Adam PJ, Madsen CS, et al. Molecular mechanisms of decreased smooth muscle differentiation marker expression after vascular injury. J Clin Invest 2000;106:1139-47.

    Google Scholar 

  • Bochaton-Piallat ML, Ropraz P, Gabbiani F, et al. Phenotypic heterogeneity of rat arterial smooth muscle cell clones. Implications for the development of experimental intimal thickening. Arterioscler Thromb Vasc Biol 1996;16:815-20.

    Google Scholar 

  • Hao H, Ropraz P, Verin V, et al. Heterogeneity of smooth muscle cell populations cultured from pig coronary artery. Arterioscler Thromb Vasc Biol 2002;22:1093-9.

    Google Scholar 

  • Moiseeva EP. Adhesion receptors of vascular smooth muscle cells and their functions. Cardiovasc Res 2001;52:372-86.

    Google Scholar 

  • Ko YS, Yeh HI, Haw M, et al. Differential expression of connexin43 and desmin defines two subpopulations of medial smooth muscle cells in the human internal mammary artery. Arterioscler Thromb Vasc Biol 1999;19:1669-80.

    Google Scholar 

  • Frid MG, Aldashev AA, Dempsey EC, et al. Smooth muscle cells isolated from discrete compartments of the mature vascular media exhibit unique phenotypes and distinct growth capabilities. Circ Res 1997;81:940-52.

    Google Scholar 

  • Li S, Fan YS, Chow LH, et al. Innate diversity of adult human arterial smooth muscle cells: cloning of distinct subtypes from the internal thoracic artery. Circ Res 2001;89:517-25.

    Google Scholar 

  • Li S, Sims S, Jiao Y, et al. Evidence from a novel human cell clone that adult vascular smooth muscle cells can convert reversibly between noncontractile and contractile phenotypes. Circ Res 1999; 85:338-48.

  • Bochaton-Piallat ML, Clowes AW, Clowes MM, et al. Cultured arterial smooth muscle cells maintain distinct phenotypes when implanted into carotid artery. Arterioscler Thromb Vasc Biol 2001; 21:949-54.

    Google Scholar 

  • Belaguli NS, Zhou W, Trinh TH, et al. Dominant negative murine serum response factor: alternative splicing within the activation domain inhibits transactivation of serum response factor binding targets. Mol Cell Biol 1999;19:4582-91.

    Google Scholar 

  • Wang D, Chang PS, Wang Z, et al. Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor. Cell 2001;105:851-62.

    Google Scholar 

  • Hellstrom M, Kalen M, Lindahl P, et al. Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 1999;126:3047-55.

    Google Scholar 

  • Schattemann GC, Loushin C, Li T, et al. PDGF-A is required for normal murine cardiovascular development. Dev Biol 1996;176: 133-42.

    Google Scholar 

  • Li X, Van Putten V, Zarinetchi F, et al. Suppression of smoothmuscle alpha-actin expression by platelet-derived growth factor in vascular smooth-muscle cells involves Ras and cytosolic phospholipase A2. Biochem J 1997;327(Pt 3):709-16.

    Google Scholar 

  • Kotani M, Fukuda N, Ando H, et al. Chimeric DNA-RNA hammerhead ribozyme targeting PDGF A-chain mRNA specifically inhibits neointima formation in rat carotid artery after balloon injury. Cardiovasc Res 2003;57:265-76.

    Google Scholar 

  • Deguchi J, Namba T, Hamada H, et al. Targeting endogenous platelet-derived growth factor B-chain by adenovirus-mediated gene transfer potently inhibits in vivo smooth muscle proliferation after arterial injury. Gene Ther 1999;6:956-65.

    Google Scholar 

  • Sanford LP, Ormsby I, Gittenberger-de Groot AC, et al. TGFbeta2 knockout mice have multiple developmental defects that are nonoverlapping with other TGFbeta knockout phenotypes. Development 1997;124:2659-70.

    Google Scholar 

  • Shah NM, Groves AK, Anderson DJ. Alternative neural crest cell fates are instructively promoted by TGFbeta superfamily members. Cell 199 6;85:331-43.

  • Sinha S, Hoofnagle MH, Kingston PA, et al. Transforming growth factor-{beta}1 signaling contributes to development of smooth muscle cells from embryonic stem cells. Am J Physiol Cell Physiol 2004;287:C1560-8.

    Google Scholar 

  • Hautmann MB, Madsen CS, Owens GK. A transforming growth factor beta (TGFbeta) control element drives TGFbeta-induced stimulation of smooth muscle alpha-actin gene expression in concert with two CArG elements. J Biol Chem 1997;272:10948-56.

    Google Scholar 

  • Moustakas A, Pardali K, Gaal A, et al. Mechanisms of TGF-beta signaling in regulation of cell growth and differentiation. Immunol Lett 2002;82:85-91.

    Google Scholar 

  • Hocevar BA, Howe PH. Analysis of TGF-beta-mediated synthesis of extracellular matrix components. Methods Mol Biol 2000;142: 55-65.

    Google Scholar 

  • Engelse MA, Lardenoye JH, Neele JM, et al. Adenoviral activin a expression prevents intimal hyperplasia in human and murine blood vessels by maintaining the contractile smooth muscle cell phenotype. Circ Res 2002;90:1128-34.

    Google Scholar 

  • Colbert MC, Kirby ML, Robbins J. Endogenous retinoic acid signaling colocalizes with advanced expression of the adult smooth muscle myosin heavy chain isoform during development of the ductus arteriosus. Circ Res 1996;78:790-8.

    Google Scholar 

  • Drab M, Haller H, Bychkov R, et al. From totipotent embryonic stem cells to spontaneously contracting smooth muscle cells: a retinoic acid and db-cAMP in vitro differentiation model. Faseb J 1997;11:905-15.

    Google Scholar 

  • Miano JM, Kelly LA, Artacho CA, et al. all-Trans-retinoic acid reduces neointimal formation and promotes favorable geometric remodeling of the rat carotid artery after balloon withdrawal injury. Circulation 1998;98:1219-27.

    Google Scholar 

  • Chen S, Gardner DG. Retinoic acid uses divergent mechanisms to activate or suppress mitogenesis in rat aortic smooth muscle cells. J Clin Invest 1998;102:653-62.

    Google Scholar 

  • Johst U, Betsch A, Wiskirchen J, et al. All-Trans and 9-cis Retinoid Acids Inhibit Proliferation, Migration, and Synthesis of Extracellular Matrix of Human Vascular Smooth Muscle Cells by Inducing Differentiation In Vitro. J Cardiovasc Pharmacol 2003;41:526-35.

    Google Scholar 

  • Wang Z, Rao PJ, Castresana MR, et al. TNF-alpha induces proliferation or apoptosis in human saphenous vein smooth muscle cells depending on phenotype. Am J Physiol Heart Circ Physiol 2005;288:H293-301.

    Google Scholar 

  • Bascands JL, Girolami JP, Troly M, et al. Angiotensin II induces phenotype-dependent apoptosis in vascular smooth muscle cells. Hypertension 2001;38:1294-9.

    Google Scholar 

  • Hayashi K, Shibata K, Morita T, et al. Insulin receptor substrate- 1/SHP-2 interaction, a phenotype-dependent switching machinery of insulin-like growth factor-I signaling in vascular smooth muscle cells. J Biol Chem 2004;279:40807-18.

    Google Scholar 

  • Tran PK, Tran-Lundmark K, Soininen R, et al. Increased intimal hyperplasia and smooth muscle cell proliferation in transgenic mice with heparan sulfate-deficient perlecan. Circ Res 2004;94:550-8.

    Google Scholar 

  • Koyama N, Kinsella MG, Wight TN, et al. Heparan sulfate proteoglycans mediate a potent inhibitory signal for migration of vascular smooth muscle cells. Circ Res 1998;83:305-13.

    Google Scholar 

  • Ichii T, Koyama H, Tanaka S, et al. Fibrillar collagen specifically regulates human vascular smooth muscle cell genes involved in cellular responses and the pericellular matrix environment. Circ Res 2001;88:460-7.

    Google Scholar 

  • Raines EW, Koyama H, Carragher NO. The extracellular matrix dynamically regulates smooth muscle cell responsiveness to PDGF. Ann N Y Acad Sci 2000;902:39-51; discussion 51-2.

    Google Scholar 

  • Li S, Chow LH, Pickering JG. Cell surface-bound collagenase-1 and focal substrate degradation stimulate the rear release of motile vascular smooth muscle cells. J Biol Chem 2000;275:35384-92.

    Google Scholar 

  • Thyberg J, Hultgardh-Nilsson A. Fibronectin and the basement membrane components laminin and collagen type IV influence the phenotypic properties of subcultured rat aortic smooth muscle cells differently. Cell Tissue Res 1994;276:263-71.

    Google Scholar 

  • Kingsley K, Huff JL, Rust WL, et al. ERK1/2 mediates PDGF-BB stimulated vascular smooth muscle cell proliferation and migration on laminin-5. Biochem Biophys Res Commun 2002;293:1000-6.

    Google Scholar 

  • Hedin U, Bottger BA, Forsberg E, et al. Diverse effects of fibronectin and laminin on phenotypic properties of cultured arterial smooth muscle cells. J Cell Biol 1988;107:307-19.

    Google Scholar 

  • Evanko SP, Angello JC, Wight TN. Formation of hyaluronan- and versican-rich pericellular matrix is required for proliferation and migration of vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1999;19:1004-13.

    Google Scholar 

  • Chai S, Chai Q, Danielsen CC, et al. Overexpression of hyaluronan in the tunica media promotes the development of atherosclerosis. Circ Res 2005;96:583-91.

    Google Scholar 

  • Li S, Lao J, Chen BP, et al. Genomic analysis of smooth muscle cells in 3-dimensional collagen matrix. Faseb J 2003;17:97-9.

    Google Scholar 

  • Stegemann JP, Nerem RM. Altered response of vascular smooth muscle cells to exogenous biochemical stimulation in two- and three-dimensional culture. Exp Cell Res 2003;283:146-55.

    Google Scholar 

  • O’Callaghan CJ, Williams B. Mechanical strain-induced extracellular matrix production by human vascular smooth muscle cells: role of TGF-beta(1). Hypertension 2000;36:319-24.

    Google Scholar 

  • Reusch HP, Chan G, Ives HE, et al. Activation of JNK/SAPK and ERK by mechanical strain in vascular smooth muscle cells depends on extracellular matrix composition. Biochem Biophys Res Commun 1997;237:239-44.

    Google Scholar 

  • Birukov KG, Bardy N, Lehoux S, et al. Intraluminal pressure is essential for the maintenance of smooth muscle caldesmon and filamin content in aortic organ culture. Arterioscler Thromb Vasc Biol 1998;18:922-7.

    Google Scholar 

  • Lehoux S, Tedgui A. Signal transduction of mechanical stresses in the vascular wall. Hypertension 1998;32:338-45.

    Google Scholar 

  • Reusch P, Wagdy H, Reusch R, et al. Mechanical strain increases smooth muscle and decreases nonmuscle myosin expression in rat vascular smooth muscle cells. Circ Res 1996;79:1046-53.

    Google Scholar 

  • Hipper A, Isenberg G. Cyclic mechanical strain decreases the DNA synthesis of vascular smooth muscle cells. Pflugers Arch May 2000; 440:19-27.

    Google Scholar 

  • Birukov KG, Shirinsky VP, Stepanova OV, et al. Stretch affects phenotype and proliferation of vascular smooth muscle cells. Mol Cell Biochem 1995;144:131-9.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. www.bsl.nl/shop/

    S. S. M. Rensen

Authors
  1. S. S. M. Rensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. A. F. M. Doevendans
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. J. J. M. van Eys
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. S. M. Rensen.

Additional information

Department of Genetics and Cell Biology, Cardiovascular Research Institute Maastricht, University of Maastricht, the Netherlands

Department of Cardiology, Heart Lung Centre Utrecht, Interuniversity Cardiology Institute, the Netherlands

Department of Cardiology, Heart Lung Centre Utrecht, Interuniversity Cardiology Institute, the Netherlands

Department of Genetics and Cell Biology, Cardiovascular Research Institute Maastricht, University of Maastricht, the Netherlands

Correspondence to: S.S.M. Rensen Department of Genetics and Cell Biology, Cardiovascular Research Institute Maastricht, University of Maastricht, PO Box 616, 6200 MD Maastricht, the Netherlands.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rensen, S.S.M., Doevendans, P.A.F.M. & van Eys, G.J.J.M. Regulation and characteristics of vascular smooth muscle cell phenotypic diversity. NHJL 15, 100–108 (2007). https://doi.org/10.1007/BF03085963

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03085963

Search

Navigation