Smooth Muscle Cell Proliferation Responses in Organ Cultures of Human Saphenous Vein

  • G. D. Angelini
  • A. C. Newby


Occlusion of saphenous vein coronary artery bypass grafts remains a major limitation to the clinical benefits of the procedure, despite more than 25 years of experience [1]. Early occlusion rates can be minimized by optimizing techniques for surgical preparation [2] and anastomosis and by the use of perioperative and early post-operative antithrombotic therapy [3]. Unfortunately, no modification of technique or drug regime has been shown to reduce late vein graft occlusion [4]. This is known to result from excessive proliferation of vascular smooth muscle cells (VSMCs) and the superimposition of atheroma on the resulting thickened intima [5]. The relationship of intimal thickening to the conditions of implantation has been investigated in animal models. Briefly summarized, intimal thickening occurs only after implantation into a high-pressure (arterial) location and is not related to adventitial disruption [6, 7]. Qualitative and quantitative time course studies [8, 9] indicate also that intimal thickening occurs progressively long after the restoration of a morphologically intact endothelium and the termination of measurable platelet and leucocyte adhesion. These observations imply that intimal thickening is an intrinsic response of the vessel wall itself to the altered haemodynamics [10]. Understanding the mechanisms underlying this response may be helpful in developing strategies to reduce vein graft occlusion.


Organ Culture Saphenous Vein Vein Graft Smooth Muscle Cell Proliferation Intimal Thickening 
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  1. 1.
    Grondin CM (1984) Late results of coronary artery grafting — is there a flag on the field? J Thorac Cardiovasc Surg 87: 161–166.PubMedGoogle Scholar
  2. 2.
    Angelini GD, Bryan AJ, Williams HMJ, Morgan R, Newby AC (1990) Distention promotes platelet and leukocyte adhesion and reduces short-term patency in pig arteriovenous bypass grafts. J Thorac Cardiovasc Surg 99: 433–439.PubMedGoogle Scholar
  3. 3.
    Fuster V, Chesebro JH (1985) Aorto-coronary artery vein graft disease: experimental and clinical approach for the understanding of the role of platelets and platelet inhibitors. Circulation 72[Suppl V]: 65–70.Google Scholar
  4. 4.
    Angelini GD, Newby AC (1989) The future of saphenous vein as a coronary artery bypass conduit. Eur Heart J 10: 273–280.PubMedGoogle Scholar
  5. 5.
    Dilley RJ, McGeachie JK, Prendergast FJ (1988) A review of the histological changes in vein to artery grafts, with particular reference to intimal hyperplasia. Arch Surg 123: 691–696.PubMedCrossRefGoogle Scholar
  6. 6.
    Brody WR, Kosek JC, Angell WW (1972) Changes in vein grafts following aorto-coronary by-pass induced by pressure and ischaemia. J Thorac Cardiovasc Surg 64: 847–854.PubMedGoogle Scholar
  7. 7.
    Brody WR, Angell WW, Kosek JC (1972) Histologic fate of venous coronary artery bypass in dogs. Am J Pathol 66: 111–130.PubMedGoogle Scholar
  8. 8.
    Fonkalsrud EW, Sanchez M, Zerubavel R (1978) Morphological evaluation of canine autogenous vein grafts in the arterial circulation. Surgery 84: 253–264.PubMedGoogle Scholar
  9. 9.
    Angelini GD, Bryan AJ, Williams HMJ et al. (1992) Timecourse of medial and intimal thickening in pig arteriovenous bypass grafts: relationship to endothelial injury and cholesterol accumulation. J Thorac Cardiovasc Surg 103: 1093–1103.PubMedGoogle Scholar
  10. 10.
    Zwolak RM, Adams MC, Clowes AW (1987) Kinetics of vein graft hyperplasia: association with tangential stress. J Vasc Surg 5: 126–136.PubMedGoogle Scholar
  11. 11.
    Pederson DC, Bowyer DE (1985) Endothelial injury and healing in vitro: studies using an organ culture system. Am J Pathol 119: 264–272.PubMedGoogle Scholar
  12. 12.
    Soyombo AA, Angelini GD, Bryan AJ, Jasani B, Newby AC (1990) Intimal proliferation in an organ culture of human saphenous vein. Am Pathol 237: 1401–1410.Google Scholar
  13. 13.
    Angelini GD, Breckenridge IM, Butchart EG et al. (1985) Metabolic damage to human saphenous vein during preparation for coronary artery bypass grafting. Cardiovasc Res 19: 326–334.PubMedCrossRefGoogle Scholar
  14. 14.
    Angelini GD, Passani SL, Breckenridge IM, Newby AC (1987) Nature and pressure dependence of damage induced by distension of human saphenous vein coronary artey bypass grafts. Cardiovasc Res 21: 902–907.PubMedCrossRefGoogle Scholar
  15. 15.
    Angelini GD, Breckenridge IM, Psaila JV, Williams HM, Henderson AH, Newby AC (1987) Preparation of human saphenous vein for coronary artery bypass grafting impairs its capacity to produce porstacyclin. Cardiovasc Res 21: 28–33.PubMedCrossRefGoogle Scholar
  16. 16.
    Angelini GD, Breckenridge IM (1985) Is there a rationale for treatment with aspirin before coronary surgery? Lancet ii: 843.CrossRefGoogle Scholar
  17. 17.
    Cooper JP, Newby AC (1991) Monocyte adhesion to human saphenous vein in vitro. Atherosclerosis 91: 85–95.PubMedCrossRefGoogle Scholar
  18. 18.
    Francis SE, Hunter S, Holt CM, Gadsdon PA, Angelini GD (1992) Growth factor activity detected in serum-free culture of pig arteriovenous bypass grafts. J Cell Biochem S16A: 28.Google Scholar
  19. 19.
    Holt CM, Francis SE, Rogers S et al. (1992) Intimai proliferation in an organ culture of human internal mammary artery. Cardiovasc Res 26: 1189–1194.PubMedCrossRefGoogle Scholar
  20. 20.
    Ross R (1986) The pathogenesis of atherosclerosis-an update. N Engl J Med 314: 488–500.PubMedCrossRefGoogle Scholar
  21. 21.
    Ip JH, Fuster V, Badimon L, Badimon J, Taubman MB, Chesebro JH (1990) Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation. J Am Coll Cardiol 15: 1667–1687.PubMedCrossRefGoogle Scholar
  22. 22.
    Lindner V, Reidy MA (1991) Proliferation of smooth muscle cells after vascular injury is inhibited by an antibody against basic fibroblast growth factor. Proc Natl Acad Sci USA 88: 3739–3743.PubMedCrossRefGoogle Scholar
  23. 23.
    Angelini GD, Breckenridge IM, Williams HM, Newby AC (1987) A surgical preparative technique for human saphenous vein coronary bypass grafts which preserves medial and endothelial functional integrity. J Thorac Cardiovasc Surg 94: 393–398.PubMedGoogle Scholar
  24. 24.
    Angelini GD, Soyombo AA, Newby AC (1991) Smooth muscle cell proliferation in response to injury in an organ culture of human saphenous vein. Eur J Vasc Surg 5: 5–12.PubMedCrossRefGoogle Scholar
  25. 25.
    Cooper JP, Soyombo A, Williams A, Newby AC (1992) Monocytes inhibit intimal smooth muscle proliferation: in vitro studies with human saphenous vein. Br Heart J 68: 93.Google Scholar
  26. 26.
    Holt CM, Francis SE, Clelland C, Violaris AG, Angelini GD (1992) Neointimal proliferation and endogenous growth factor release in an organ culture of human coronary artery. J Cell Biochem S16A: 11.Google Scholar
  27. 27.
    Francis SE, Holt CM, Taylor T, Gadsdon PA, Angelini GD (1992) Another cautionary note on the use of PCNA. J Pathol 166: 418.PubMedGoogle Scholar
  28. 28.
    Buck RC (1977) Organ cultures of rat aorta: a scanning and transmission electron microscopic study. Exp Mol Pathol 26: 260–276.PubMedCrossRefGoogle Scholar
  29. 29.
    Gotlieb AI, Boden P (1984) Porcine aortic organ culture: a model to study the cellular response to vascular injury. In Vitro 20: 535–542.PubMedCrossRefGoogle Scholar
  30. 30.
    Fingerle J, Kraft T (1987) The induction of smooth muscle cell proliferation in vitro using an organ culture system. Int Angiol 6: 65–72.PubMedGoogle Scholar
  31. 31.
    Koo EWY, Gotlieb AI (1989) Endothelial stimulation of intimal cell proliferation in a porcine aortic organ culture. Am J Pathol 134: 497–503.PubMedGoogle Scholar
  32. 32.
    Soyombo A, Newby AC (1991) Inhibition of smooth muscle proliferation by cyclic nucleotides in an organ culture of human saphenous vein. J Mol Cell Cardiol 23[Suppl V]: S114.CrossRefGoogle Scholar
  33. 33.
    Francis SE, Holt CM, Taylor T, Gadsdon P, Angelini GD (1992) Heparin and intimal thickening in an organ culture of human saphenous vein. Atherosclerosis 93: 155–156.PubMedCrossRefGoogle Scholar
  34. 34.
    Thyberg J, Hedin U, Sjölund M, Palmberg L, Bottger BA (1990) Regulation of differentiated properties and proliferation of arterial smooth muscle cells. Arteriosclerosis 10: 966–990.PubMedCrossRefGoogle Scholar
  35. 35.
    Southgate KM, Davies M, Booth RFG, Newby AC (1992) Involvement of extracellular matrix degrading metalloproteinases in rabbit aortic smooth muscle cell proliferation. Biochem J 288: 93–99.PubMedGoogle Scholar
  36. 36.
    Unemori EN, Bouhanna KS, Werb Z (1990) Vectorial secretion of extracellular matrix proteins, matrix-degrading proteinases, and tissue inhibitor of metalloproteinases by endothelial cells. J Biol Chem 265: 445–451.PubMedGoogle Scholar
  37. 37.
    Reidy MA, Silver M (1985) Endothelial regeneration — lack of intimal proliferation after defined injury to rat aortas. Am J Pathol 118: 173–177.PubMedGoogle Scholar
  38. 38.
    Clowes AW, Clowes MM, Fingerle J, Reidy MA (1989) Kinetics of cellular proliferation after arterial injury — role of acute distension in the induction of smooth muscle proliferation. Lab Invest 60: 360–364.PubMedGoogle Scholar
  39. 39.
    Henney AM, Wakely PR, Davies MJ et al. (1991) Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. Proc Natl Acad Sci USA 88: 8154–8158.PubMedCrossRefGoogle Scholar
  40. 40.
    Bonchek LI (1980) Prevention of endothelial damage during preparation of saphenous veins for bypass grafting. J Thorac Cardiovasc Surg 79: 911–915.PubMedGoogle Scholar
  41. 41.
    Angelini GD, Bryan AJ, Hunter S, Newby AC (1992) A simple preparative technique which preserves human saphenous vein functional integrity during coronary artery bypass grafting. Ann Thoracic Surg 53: 871–874.CrossRefGoogle Scholar
  42. 42.
    Boerboom LE, Olinger GN, Bonchek LI et al. (1985) The relative influence of arterial pressure versus intraoperative distention on lipid accumulation in primate vein bypass grafts. J Thorac Cardiovasc Surg 90: 756–764.PubMedGoogle Scholar
  43. 43.
    Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L (1987) Beneficial effect of combined colestipolniacin therapy on coronary atherosclerosis and coronary venous bypass grafts. J Am Med Assoc 257: 3233–3240.CrossRefGoogle Scholar
  44. 44.
    Anderson JL, Baim DS, Fein SA, Goldstein RA, LeJemtel TH, Likoff MJ (1987) Efficacy and safety of sustained (48 hour) intravenous infusions of milrinone in patients with severe congestive heart failure: a multicentre study. J Amer Coll Cardiol 9: 711–722.CrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • G. D. Angelini
  • A. C. Newby

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