Skip to main content
SpringerLink
Log in

Stretch affects phenotype and proliferation of vascular smooth muscle cells

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The exertion of periodic dynamic strain on the arterial wall is hypothesized to be relevant to smooth muscle cell morphology and function. This study has investigated the effect of cyclic mechanical stretching on rabbit aortic smooth muscle cell proliferation and expression of contractile phenotype protein markers. Cells were cultured on flexible-bottomed dishes and cyclic stretch was applied (frequency 30 cycles/min, 15% elongation) using a Flexercell Strain unit. Cyclic stretch potentiated smooth muscle cell proliferation in serum-activated cultures but not in cultures maintained in 0.5% fetal calf serum. Stretching induced a serum-independent increase of h-caldesmon expression and this effect was reversible following termination of mechanical stimulation. Strain was without effect on smooth muscle myosin or calponin expression. In cells grown on laminin stretch-induced h-caldesmon expression was more prominent than in cells cultured on collagen types I and IV, poly-L-lysine and gelatin. These data suggest that cyclic mechanical stimulation possesses dual effect on vascular smooth muscle cell phenotype characteristics since it: 1) potentiates proliferation, an attribute of a dedifferentiated phenotype; and 2) increases expression of h-caldesmon considered a marker of a differentiated smooth muscle cell state.

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

Similar content being viewed by others

References

  1. Barany K, Ledvora RF, Mougios V, Barany M: Stretch-induced myosin light chain phosphorylation and stretch-release-induced tension development in arterial smooth muscle. J Biol Chem 260: 7126–7130, 1985

    PubMed  Google Scholar 

  2. Schwartz SM, Campbell GR, Campbell JH: Replication of smooth muscle cells in vasculardisease. Circ Res 58: 427–444, 1986

    PubMed  Google Scholar 

  3. Campbell GR, Campbell JH, Manderson JA, Horrigan S, Rennick RE: Arterial smooth muscle. A multifunctional mesenchymal cell. Arch Pathol Lab Med 112: 977–986, 1988

    PubMed  Google Scholar 

  4. Mosse PRL, Campbell GR, Wang ZL, Campbell JH: Smooth muscle phenotypic expression in human carotid arteries. I. Comparison of cells from diffuse intimal thickenings adjacent to atheromatous plaques with those of the media. Lab Invest 53: 556–562, 1985

    PubMed  Google Scholar 

  5. Gabbiani g, Kocher O, Bloom WS, Vandekerckhove J, Weber K: Actin expression in smooth muscle cells of rat aortic intimal thickening, human atheromatous plaque, and cultured rat aortc media. J Clin Invest 73: 148–152, 1984

    PubMed  Google Scholar 

  6. Kocher O, Skalli O, Bloom WS, Gabbiani G: Cytoskeleton of rat aortic smooth muscle cells. Normal conditions and experimental intimal thickening. Lab Invest 50: 645–652, 1984

    PubMed  Google Scholar 

  7. Zanellato AMA, Borrione AC, Tonello M, Scannapieco G, Pauletto P, Sartore S: Myosin isoform expression and smooth muscle cell heterogeneity in normal and atherosclerotic rabbit aorta. Arteriosclerosis 10: 996–1009, 1990

    PubMed  Google Scholar 

  8. Glukhova MA, Kabakov AE, Frid MG, Ornatsky OI, Belkin AM, Mukhin DN, Orekhov AN, Koteliansky VE, Smirnov VN: 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 85: 9542–9546, 1988

    PubMed  Google Scholar 

  9. Sadoshima J, Jahn L, Takahashi T, Kulik T, Izumo S: Molecular characterization of the stretch-induced adaptation of cultured cardiac cells. J Biol Chem 267: 10551–10560, 1992

    PubMed  Google Scholar 

  10. Comuro I, Katoh Y, Toshikazu K, Shibazaki Y, Kurabayashi M, Hoh E, Takaku F, Yazaki Y: Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes. J Biol Chem 266: 1265–1268, 1991

    PubMed  Google Scholar 

  11. Gardner DG, Wirtz H, Dobbs LG: Stretch-dependent regulation of atrial peptide synthesis and secretion in cultured atrial cardiocytes. Am J Physiol 263: E239-E244, 1992

    PubMed  Google Scholar 

  12. Sumpio BE, Banes AJ: Prostacyclin synthetic activity in cultured aortic endothelial cells undergoing cyclic mechanical deformation. Surgery 104: 383–389, 1988

    PubMed  Google Scholar 

  13. Iba T, Shin T, Sonoda T, Rosales O, Sumpio BE: Stimulation of endothelial secretion of tissue-type plasminogen activator by repetitive stretch. J Surg Res 50: 457–460, 1991

    PubMed  Google Scholar 

  14. Sumpio BE, Banes AJ, Levin LG, Johnson G: Mechanical stress stimulates aortic endothelial cells to proliferate. J Vasc Surg 6: 252–256, 1987

    PubMed  Google Scholar 

  15. Leung DY, Glagov S, Mathews MB: Cyclic stretching stimulates synthesis of matrix components by arterial smooth muscle cellsin vitro. Science (Wash. DC) 191: 475–477, 1976

    Google Scholar 

  16. Wilson E, Mai Q, Sudhir K, Weiss RH, Ives HE: Mechanical strain induces growth of Vascular smooth muscle cells via autocrine action of PDGF. J Cell Biol 123: 741–747, 1993

    PubMed  Google Scholar 

  17. Hayashi K, Yano H, Hashida T, Takeuchi R, Takeda O, Asada K, Takahashi E, Kato I, Sobue K: Genomic structure of the human caldesmon gene. Proc Natl Acad Sci USA 89: 12122–12126, 1992

    PubMed  Google Scholar 

  18. Makuch R, Birukov K, Shirinsky V, Dabrowska R: Functional interrelationship between calponin and caldesmon. Biochem J 280: 33–38, 1991

    PubMed  Google Scholar 

  19. Gimona M, Herzog M, Vandekerckhove J, Small JV: Smooth muscle specific expression of calponin. FEBS Lett 274: 159–162, 1990

    PubMed  Google Scholar 

  20. Birukov KG, Frid MG, Rogers JD, Shirinsky VP, Koteliansky VE, Campbell JH, Campbell GR: Synthesis and expression of smooth muscle phenotypmarkers in primary culture of rabbit smooth muscle cells: influence of seeding density and media and relation to cell contractility. Exp Cell Res 204: 46–53, 1993

    PubMed  Google Scholar 

  21. Chamley-Campbell JH, Campbell GR, Ross R: The smooth muscle cell in culture. Physiol Rev 59: 1–61, 1979

    PubMed  Google Scholar 

  22. Shirinsky VP, Antonov AS, Birukov KG, Sobolevsky AV, Romanov YuA, Kabaeva NV, Antonova GN, Smirnov VN: Mechano-chemical control of human endothelium orientation and size. J Cell Biol 109: 331–339, 1989

    PubMed  Google Scholar 

  23. Shirinsky VP, Biryukov KG, Vorotnikov AV, Gusev NB: Caldesmon 150, caldesmon 77 and skeletal muscle troponin T share a common antigenic determinant. FEBS Lett 251: 65–68, 1989

    PubMed  Google Scholar 

  24. Birukov KG, Stepanova OV, Nanev AK, Shirinsky VP: Expression of calponin in rabbit nd human aortic smooth muscle cells. Cell Tis Res 266: 579–584, 1991

    Google Scholar 

  25. Nanaev AK, Shirinsky VP, Birukov KG: Immunofluorescent study of heterogeneity in smooth muscle cells of human fetal vessels using antibodies to myosin, desmin, and vimentin. Cell Tis Res 266: 535–540, 1991

    Google Scholar 

  26. Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685, 1970

    PubMed  Google Scholar 

  27. Towbin H, Staehelin T, Gordon J: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76: 4350–4354, 1979

    PubMed  Google Scholar 

  28. Shirinsky VP, Birukov KG, Koteliansky VE, Glukhova MA, Spanidis E, Rogers JD, Campbell JH, Campbell GR: Density-related expression of caldesmon and vinculin in cultured rabbit aortic smooth muscle cells. Exp Cell Res 194: 186–189, 1991

    PubMed  Google Scholar 

  29. Shirinsky VP, Birukov KG, Sobolevsky AV, Vedernikov YuP, Posin EYa, Popov EG: Contractile rabbit aortic smooth muscle cells in culture. Preparation and characterization. Am J Hypertension 5: 124S-130S, 1992

    Google Scholar 

  30. Holycross BJ, Blank RS, Thompson MM, Peach MJ, Owens GK: Platelet-derived growth factor-BB-induced suppression of smooth muscle cell differentiation. Circ Res 71: 1525–1532, 1992

    PubMed  Google Scholar 

  31. Yamamoto M, Yamamoto K, Noumura T: Type I collagen promotes modulation of cultured rabbit arterial smooth muscle cells from a contractile to a synthetic phenotype. Exp Cell Res 204: 121–129, 1993

    PubMed  Google Scholar 

  32. Hedin U, Bottger BA, Forsberg E, Johansson S, Thyberg J: Diverse effects of fibronectin and laminin on phenotypic properties of cultured arterial smooth muscle cells. J Cell Biol 107: 307–319, 1988

    PubMed  Google Scholar 

  33. Schaller MD, Parsons JT: Focal adhesion kinase: an integrin-linked protein tyrosine kinase. Trends Cell Biol 3: 258–262, 1993

    PubMed  Google Scholar 

  34. Kornberg LJ, Earp HS, Turner CE, Prockop C, Juliano RL: Signal transduction by integrins: increased protein tyrosine phosphorylation caused by clustering of beta 1 integrins. Proc Natl Acad Sci USA 88: 8392–8396, 1991

    PubMed  Google Scholar 

  35. Seifert RA, Schwartz SM, Bowen-Pope DF: Developmentally regulated production of platelet-derived growth factor-like molecules. Nature 311: 669–671, 1984

    PubMed  Google Scholar 

  36. Morisaki N, Kanzaki T, Koshikawa T, Saito Y, Yoshida S: Secretion of a new growth factor, smooth muscle cell derived growth factor, distinct from platelet derived growth factor by cultured rabbi aortic smooth muscle cells. FEBS Lett 230: 186–190, 1988

    PubMed  Google Scholar 

  37. Naruse K, Sokabe M: Involvement of stretch-activated ion channels in Ca2+ mobilization to mechanical stretch in endothelial cells. Am J Physiol 264: C1037-C1044, 1993

    PubMed  Google Scholar 

  38. Berk BC, Alexander RW, Brock TA, Gimbrone MA Jr, Webb RC: Vasoconstriction: a new activity for platelet-derived growth factor. Science 232: 87–90, 1986

    PubMed  Google Scholar 

  39. Berk BC, Alexander RW: Vasoactive effects of growth factors. Biochem Pharmacol 38: 219–225, 1989

    PubMed  Google Scholar 

  40. Nilsson J, Sjolund M, Palmberg L, Von Euler AM, Jonzon B, Thyberg J: The calcium antagonist nifedipine inhibits arterial smooth muscle cell proliferation. Atherosclerosis 58: 109–122, 1985

    PubMed  Google Scholar 

  41. Corjay MH, Thompson MM, Lynch KR, Owens GK: Differential effect of platelet-derived growth factor versus serum-induced growth on smooth muscle alpha-actin and nonmuscle beta-actin mRNA expression and growth state in cultured rat aortic smooth muscle cells. J Biol Chem 264: 10501–10506, 1989

    PubMed  Google Scholar 

  42. Desmouliere A, Rubbia-Brandt L, Gabbiani G: Modulation of actin isoform expression in cultured arterial smooth muscle cells by heparin and culture conditions. Arteriosclerosis and Thrombosis 11: 244–253, 1991

    PubMed  Google Scholar 

  43. Ueki N, Sobue K, Kanda K, Hada T, Higashino K: Expression of high and low molecular weight caldesmons during phenotypic modulation of smooth muscle cells. Proc Natl Acad Sci USA 84: 9049–9053, 1987

    PubMed  Google Scholar 

  44. Reckless J, Fleetwood G, Tilling L, Huber PAJ, Marston SB, Pritchard K: Changes in the caldesmon isoform content and intimal thickening in the rabbit carotid artery induced by a silicone elastomer collar. Arterioscler Thromb 14: 1837–1845, 1994

    PubMed  Google Scholar 

  45. McDonald JA: Receptors for extracellular matrix components. Am J Physiol 257: L331-L337, 1989

    PubMed  Google Scholar 

  46. Davis MJ, Donovitz JA, Hood JD: Stretch-activated single-channel and whole cell currents in vascular smooth muscle cells. Am J Physiol 262: C1083-C1088, 1992

    PubMed  Google Scholar 

  47. Bialecki RA, Kulik TJ, Colucci WS: Stretching increases calcium influx and efflux in cultured pulmonary arterial smooth muscle cells. Am J Physiol 263: L602-L606, 1992

    PubMed  Google Scholar 

  48. Kulik TJ, Bialecki RA, Colucci WS, Rothmann A, Glennon T, Underwood RH: Stretch increases inositol trisphosphate and inositol tetrakisphosphate in cultured pulmonary vascular smooth muscle cells. Biochem Biophys Res Commun 180: 983–987, 1991

    Google Scholar 

  49. Letsou GV, Rosales O, Maitz S, Vogt A, Sumpio BE: Stimulation of adenylate cyclase activity in cultured endothelial cells subjected to cyclic stretch. J Cardiovasc Surg 31: 634–639, 1990

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Molecular Endocrinology, Cardiology Research Center of the Russian Academy of Medical Sciences, 121552, Moscow, Russia

    Konstantin G. Birukov, Vladimir P. Shirinsky, Olga V. Stepanova, Vsevolod A. Tkachuk & Vladimir N. Smirnov

  2. Department of Research, Basel University Hospitals, CH-4031, Basel, Switzerland

    Alfred W. A. Hahn & Terese J. Resink

Authors
  1. Konstantin G. Birukov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vladimir P. Shirinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olga V. Stepanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vsevolod A. Tkachuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alfred W. A. Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Terese J. Resink
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vladimir N. Smirnov
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Birukov, K.G., Shirinsky, V.P., Stepanova, O.V. et al. Stretch affects phenotype and proliferation of vascular smooth muscle cells. Mol Cell Biochem 144, 131–139 (1995). https://doi.org/10.1007/BF00944392

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00944392

Key words

Search

Navigation