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Thromb Haemost 1999; 81(02): 293-300
DOI: 10.1055/s-0037-1614460
Review Articles
Schattauer GmbH

Effect of Pulse Pressure on Vascular Smooth Muscle Cell Migration: The Role of Urokinase and Matrix Metalloproteinase

Eileen M. Redmond
1   From the Department of Surgery, Washington, DC, USA
,
Paul A. Cahill
1   From the Department of Surgery, Washington, DC, USA
,
Mindy Hirsch
2   Department of Medicine, Georgetown University Medical Center, Washington, DC, USA
,
Yi-Ning Wang
1   From the Department of Surgery, Washington, DC, USA
,
James V. Sitzmann
1   From the Department of Surgery, Washington, DC, USA
,
Steve S. Okada
2   Department of Medicine, Georgetown University Medical Center, Washington, DC, USA
› Author AffiliationsThis work was supported by grants from the National Institutes of Health (DK09223 to EMR; HL59696 to PAC; DK47067 to JVS; HL02870 to SSO), an American Heart Association Established Investigator Award (to SSO) and a Grant-in-Aid from the Alcoholic Beverage Medical Research Foundation (EMR).
Further Information

Publication History

Received18 May 1998

Accepted after resubmission13 October 1998

Publication Date:
08 December 2017 (online)

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Summary

Plasminogen activator (PA) expression plays an important role in smooth muscle cell (SMC) migration and may therefore contribute to mechanical force-induced arterialization of vein grafts. The aim of this study was to determine whether pulse pressure due to pulsatile flow modulates SMC migration via urokinase (u-PA)-dependent mechanisms. Using a perfused transcapillary culture system, human umbilical vein SMC were exposed to pulse pressures (0-56 mmHg), in the absence or presence of human umbilical vein endothelial cells (EC) by varying pulsatile flow rates (0 ml/min to 25 ml/min). SMC cultured in the absence of EC increased their migration following exposure to increased pulse pressure (248 ± 14%). Both u-PA and matrix metalloproteinase 1 (MMP-1) expression was significantly elevated in SMC exposed to pressure as compared to static controls. The role of proteases in the pulse pressure-induced enhancement of SMC migration was confirmed following pretreatment with aprotinin, an anti u-PA antibody and metalloproteinase inhibitors (181 ± 14% for aprotinin vs. 256 ± 25% for control, 108 ± 4% for anti-u-PA antibody vs. 233 ± 17% for non-immune IgG, and 114 ± 9% for BB-94, 105 ± 7% for BB-3103 vs. 222 ± 5% for control). Using SMC derived from u-PA gene knockout mice, the SMC migratory response to increased pulse pressure was completely inhibited despite a significant increase in MMP expression in these cells. These results suggest that pulse pressure due to pulsatile flow induces SMC migration in vitro via u-PA and MMP-dependent mechanisms. Moreover, u-PA gene deletion results in blunting of pressure-induced SMC migration despite the endogenous upregulation of metalloproteinase. Modulation of u-PA expression by pressure may thus represent an important mechanism whereby hemodynamic forces regulate smooth muscle cell migration.

 

  • References

  • 1 Schwartz LB, O’Donohoe MK, Purut CM, Mikat EM, Hagen P-O, McCann RL. Myointimal thickening in experimental vein grafts is dependent on wall tension. J Vasc Surg 1992; 15: 176-86.
    CrossrefPubMedGoogle Scholar
  • 2 Zwolak RM, Adams MC, Clowes AW. Kinetics of vein graft hyperplasia: association with tangential stress. J Vasc Surg 1987; 5: 126-36.
    CrossrefPubMedGoogle Scholar
  • 3 Amano J, Suzuki A, Sunamori M, Tsukada T, Numano F. Cytokinetic study of aortocoronary bypass vein grafts in place for less than six months. Am J Cardiol 1991; 67: 1234-6.
    CrossrefPubMedGoogle Scholar
  • 4 Osol G. Mechanotransduction by vascular smooth muscle. J Vasc Res 1995; 32: 275-92.
    CrossrefPubMedGoogle Scholar
  • 5 Reusch P, Wagdy H, Reusch R, Wilson E, Ives HE. Mechanical strain increases smooth muscle and decreases nonmuscle myosin expression in rat vascular smooth muscle cells. Circ Res 1996; 79: 1046-53.
    CrossrefPubMedGoogle Scholar
  • 6 Hamada K, Takuwa N, Yokoyma K, Takuwa Y. Stretch activates Jun N-terminal kinase/stre-activated protein kinase in vascular smooth muscle cells through mechanisms involving autocrine ATP stimulation of purinoceptors. Journal of Biological Chemistry 1998; 13: 6334-40.
    PubMedGoogle Scholar
  • 7 Clowes AW, Clowes MM, Au YP, Reidy MA, Belin D. Smooth muscle cells express urokinase during mitogenesis and tissue-type plasminogen activator during migration in injured rat carotid artery. Circ Res 1990; 67: 61-7.
    CrossrefPubMedGoogle Scholar
  • 8 Wijnberg MJ, Quax PH, Nieuwenbroek NME, Verherijen JH. The migration of human smooth muscle cells in vitro is mediated by plasminogen activation and can be inhibited by α2-macroglobulin receptor associated protein. Thromb Haemost 1997; 78: 880-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Lupu F, Heim DA, Bachmann F, Hurni M, Kakkar VV, Kruithof EK. Plasminogen activator expression in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol 1995; 15: 1444-55.
    CrossrefPubMedGoogle Scholar
  • 10 Raghunath PN, Tomaszewski JT, Brady ST, Caron RJ, Okada SS, Barnathan ES. Plasminogen activator system in human coronary atherosclerosis. Arterioscler Thromb Vasc Biol 1995; 15: 1432-43.
    CrossrefPubMedGoogle Scholar
  • 11 Carmeliet P, Moons L, Herbert J-M, et al. Urokinase but not tissue plasminogen activator mediates arterial neointima formation in mice. Circ Res 1997; 81: 829-39.
    CrossrefPubMedGoogle Scholar
  • 12 Ueba H, Kawakami M, Yaginuma T. Shear stress as an inhibitor of vascular smooth muscle cell proliferation. Role of transforming growth factor-β1 and tissue-type plasminogen activator. Arterioscler Thromb Vasc Biol 1997; 17: 1512-6.
    CrossrefPubMedGoogle Scholar
  • 13 Redmond EM, Cahill PA, Sitzmann JV. Perfused transcapillary smooth muscle cells and endothelial cell co-culture: A novel in vitro model. In Vitro Cell Dev Biol 1995; 31: 601-9.
    CrossrefPubMedGoogle Scholar
  • 14 Redmond EM, Cahill PA, Sitzmann JV. Flow-mediated regulation of endothelin receptors in cocultured vascular smooth muscle cells: An endothelium-dependent effect. J Vasc Res 1997; 34: 425-35.
    CrossrefPubMedGoogle Scholar
  • 15 Grobmyer SR, Kuo A, Orishimo M, Okada S, Cines DB, Barnathan ES. Determinants of binding and internalization of tissue-type plasminogen activator by human vascular smooth muscle and endothelial cells. J Biol Chem 1993; 268: 13291-300.
    PubMedGoogle Scholar
  • 16 Quinn CO, Scott DK, Brinckerhoff CE, Matrisian LM, Jeffrey JJ, Partridge NC. Rat collagenase. Cloning, amino acid sequence comparison and parathyroid hormone regulation in osteoblastic cells. J Biol Chem 1990; 265: 22343-7.
    PubMedGoogle Scholar
  • 17 Langer DJ, Kuo A, Kariko K. et al Regulation of the endothelial cell urokinase-type plasminogen activator receptor: Evidence for cAMP dependent and protein kinase C dependent pathways. Circ Res 1993; 72: 330-40.
    CrossrefPubMedGoogle Scholar
  • 18 Kenagy RD, Vergel S, Mattson E, Bendeck M, Reidy MA, Clowes AW. The role of plasminogen, plasminogen activators, and matrix metalloproteinases in primate arterial smooth muscle cell migration. Arteroscler Thromb Vasc Biol 1996; 16: 1373-82.
    CrossrefPubMedGoogle Scholar
  • 19 Gross JL, Moscatelli D, Jaffe EA, Rifkin DB. Plasminogen activator and collagenase production by cultured capillary endothelial cells. J Cell Biol 1982; 95: 974-81.
    CrossrefPubMedGoogle Scholar
  • 20 Parks WC, Mecham RP. Interstitial Collagenases. In: Matrix Metalloproteinases. Parks WC, Mecham RP. (eds) New York: Academic Press; 1998
    Google Scholar
  • 21 Takahashi M, Ishida T, Traub O, Corson MA, Berk BC. Mechanotransduction in endothelial cells: Temporal signaling events in response to shear stress. J Vasc Res 1997; 34: 212-9.
    CrossrefPubMedGoogle Scholar
  • 22 Malek AM, Izumo S. Mechanism of endothelial cell shape change and cytoskeletal remodeling in reponse to fluid shear stress. J Cell Sci 1996; 109: 713-26.
    PubMedGoogle Scholar
  • 23 Frangos JA, Eskin SG, McIntire LV, Ives CL. Flow effects on prostacyclin production by cultured endothelial cells. Science 1985; 227: 1477-9.
    CrossrefPubMedGoogle Scholar
  • 24 Hsieh HJ, Li NQ, Frangos JA. Shear stress increases endothelial platelet derived growth factor mRNA levels. Am J Physiol 1991; 260: H642-H646.
    PubMedGoogle Scholar
  • 25 Yoshizumi M, Kurihara T, Sugiyama F. et al Hemodynamic shear stress stimulates endothelin production by cultured endothelial cells. Biochem Biophys Res Comm 1989; 161: 859-64.
    CrossrefPubMedGoogle Scholar
  • 26 Gibbons GH, Dzau V. The emerging concept of vascular remodeling. New Eng J Med 1994; 330: 1431-8.
    CrossrefPubMedGoogle Scholar
  • 27 Tseng H, Peterson TE, Berk BC. Fluid shear stress stimulates mitogen activated protein kinase in endothelial cells. Circ Res 1995; 77: 869-78.
    CrossrefPubMedGoogle Scholar
  • 28 Ohno M, Cooke JD, Dzau V, Gibbons GH. Fluid shear stress induces endothelial transforming growth factor β-1 transcription and production. J Clin Invest 1995; 95: 1363-9.
    CrossrefPubMedGoogle Scholar
  • 29 Leimgruber PP, Roubin GS, Hallman J. et al Restenosis after successful coronary angioplasty in patients with single vessel disease. Circ 1986; 73: 710-7.
    CrossrefPubMedGoogle Scholar
  • 30 Lindner V, Giachelli CM, Schwartz SM, Reidy MA. A subpopulation of smooth muscle cells in injured rat arteries expresses platelet-derived growth factor-B chain mRNA. Circ Res 1995; 76: 951-7.
    CrossrefPubMedGoogle Scholar
  • 31 Diamond SL, Sharefkin JB, Dieffenbach S, Frasier-Scott K, McIntire LV, Eskin SG. Tissue plasminogen activator messenger RNA levels increase in cultured human endothelial cells exposed to laminar shear stress. J Cell Physiol 1990; 143: 364-71.
    CrossrefPubMedGoogle Scholar
  • 32 Carmeliet P, Moons L, Lijnen R. et al Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nature Gen 1997; 17: 439-44.
    CrossrefPubMedGoogle Scholar
  • 33 Davies PF. Flow-mediated endothelial mechanotransduction. Physiol Rev 1995; 75: 519-60.
    CrossrefPubMedGoogle Scholar
  • 34 Yano Y, Geibel J, Sumpio BE. Tyrosine phosphorylation of pp125FAK and paxillin in aortic endothelial cells induced by mechanical strain. Am J Physiol 1996; 271 (2 pt1) C635-C649.
    CrossrefPubMedGoogle Scholar
  • 35 Wilson E, Sudhir K, Ives HE. Mechanical strain of rat vascular smooth muscle cells is sensed by specific extracellular matrix/integrin interactions. J Clin Invest 1995; 96: 2364-72.
    CrossrefPubMedGoogle Scholar
  • 36 Chang AW, Kuo A, Barnathan ES, Okada SS. Urokinase receptor-dependent upregulation of smooth muscle cell adhesion to vitronectin by urokinase. Arterioscler Thromb Vasc Biol. 1998 (in press).
    PubMedGoogle Scholar