Mechanisms of Plaque Formation and Occlusion in Venous Coronary Bypass Grafts

  • I. K. Jang
  • V. Fuster


The progression of venous coronary bypass graft disease can be divided into three phases [12]: (a) acute thrombotic phase, (b) intimai hyperplasia, and (c) atherosclerosis (Fig. 1). Acute thrombotic occlusion occurs within the first month after operation and is mediated mainly by platelets. Between 1 and 12 months after operation smooth muscle cells begin to proliferate, and connective tissue synthesis increases. After 3 years atherosclerotic lesions progress further, and the natural history of venous bypass grafts becomes similar to that of native coronary arteries with advanced atherosclerosis.


Smooth Muscle Cell Intimal Hyperplasia Smooth Muscle Cell Proliferation Atheromatous Plaque Platelet Deposition 
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  1. 1.
    Ausprunk DH, Boudreau CL, Nelson DA (1981) Proteoglycans in the microvasculature. I. Histochemical localization in microvessels of the rabbit. Am J Pathol 103: 353–366.PubMedGoogle Scholar
  2. 2.
    Badimon L, Badimon JJ, Turitto VT, Fuster V (1987) Platelet deposition in von Willebrand factor deficient vessel wall. J Lab Clin Med 110: 634–647.PubMedGoogle Scholar
  3. 3.
    Badimon L, Badimon JJ, Turitto VT, Vallabhajosuia S, Fuster V (1988) Platelet thrombus formation on collagen type I. Influence of blood rheology, von Willebrand factor and blood coagulation. Circulation 78: 1431–1442.PubMedCrossRefGoogle Scholar
  4. 4.
    Berk BC, Taubman MB, Gragoe EJ, Fenton FW, Griendling KK (1990) Thrombin signal transduction mechanism in rat vascular smooth muscle cells. Calcium and protein kinase C-dependent and-independent pathways. J Biol Chem 265: 17334–17440.PubMedGoogle Scholar
  5. 5.
    Bini A, Fenoglio JJ, Mes-Tejada R, Kerdryk B, Kaplan KL (1989) Identification and distribution of fibrinogen, fibrin and fibrin (ogen) degradation products in atherosclerosis: use of monoclonal antibodies. Atherosclerosis 1: 109–121.Google Scholar
  6. 6.
    Bulkley BH, Hutchins GM (1978) Pathology of coronary artery bypass graft surgery. Arch Pathol Lab Med 102: 273–280.PubMedGoogle Scholar
  7. 7.
    Campbell GR, Campbell JH (1985) Smooth muscle phenotypic changes in arterial wall homeostasis: implication for the pathogenesis of atherosclerosis. Exp Mol Pathol 42: 139–162.PubMedCrossRefGoogle Scholar
  8. 8.
    Campeau L, Enjalbert M, Lesperance J, Bourassa MG, Kwiterovich P, Wacholder S, Sniderman A (1984) The relation of risk factors to the development of atherosclerosis in saphenous-vein bypass grafts and the progression of disease in the native circulation. N Engl J Med 311: 1329–1332.PubMedCrossRefGoogle Scholar
  9. 9.
    Caplan AI, Fizman MC, Eppenbeiger HM (1983) Molecular and cell isoforms during development. Science 221: 921–927.PubMedCrossRefGoogle Scholar
  10. 10.
    Castellot JJ, Addonizio ML, Rosenberg R, Karnovsky MJ (1981) Cultured endothelial cells produce a heparin-like inhibitor of smooth muscle cell growth. J Cell Biol 90: 372–377.PubMedCrossRefGoogle Scholar
  11. 11.
    Chamley-Campbell JH, Campbell GR, Ross R (1979) The smooth muscle cell in culture. Physiol Rev 59: 1–61.PubMedGoogle Scholar
  12. 12.
    Chesebro JH, Goldman S (1992) Coronary artery bypass surgery: antithrombotic therapy. In: Fuster V, Verstraete M (eds) Thrombosis in cardiovascular disorders. Saunders, Philadelphia, pp 375–388.Google Scholar
  13. 13.
    Chesebro JH, Clements IP, Fuster V, Elveback LR, Smith HC, Bardsley WT, Frye RL, Homes DR, Vlietstra RE, Pluth JR, Wallace RB, Puga FJ, Orszulak TA, Piehler JM, Schaff HV, Danielson GK (1982) A platelet-inhibitor-drug trial in coronary-artery bypass operations: benefit of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency. N Engl J Med 307: 73–78.PubMedCrossRefGoogle Scholar
  14. 14.
    Clowes AW, Schwartz SM (1985) Significance of quiescent smooth muscle migration in the injured rat carotid artery. Circ Res 56: 139–145.PubMedGoogle Scholar
  15. 15.
    Clowes AW, Reidy MA, Clowes NM (1983) Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. Lab Invest 49: 327–333.PubMedGoogle Scholar
  16. 16.
    Cunningham DD, Farrell DH (1986) Thrombin interaction with cultured fibroblasts: relationship to mitogenic stimulation. Ann NY Acad Sci 485: 240–248.PubMedCrossRefGoogle Scholar
  17. 17.
    Davies MJ, Thomas AC (1985) Plaque fissuring: the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina. Br Heart J 53: 363–373.PubMedCrossRefGoogle Scholar
  18. 18.
    Davies MJ, Woolf N, Rowles PM, Pepper J (1988) Morphology of the endothelium over atherosclerotic plaques in human coronary arteries. Br Heart J 60: 459–464.PubMedCrossRefGoogle Scholar
  19. 19.
    Davies MJ, Bland MJ, Hartgartner WR, angelini A, Thomas AC (1989) Factors influencing the presence or absence of acute coronary thrombi in sudden ischemic death. Eur Heart J 10: 203–208.PubMedGoogle Scholar
  20. 20.
    Falk E (1983) Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis: characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J 50: 127–134.PubMedCrossRefGoogle Scholar
  21. 21.
    Fingerle J, Au WPT, Clowes AW, Reidy MA (1990) Intimai lesion formation in rat carotid arteries after endothelial denudation in absence of medial injury. Arteriosclerosis 10: 1082–1087.PubMedCrossRefGoogle Scholar
  22. 22.
    Fishman JA, Ryan GB, Kamorsky MI (1977) Endothelial regeneration in the rat carotid artery and the significance of endothelial denudation in the pathogenesis of myointimal thickening. Lab Invest 32: 339–351.Google Scholar
  23. 23.
    Friedman M, van den Bovenkamp GJ (1966) The pathogenesis of a coronary thrombus. Am J Pathol 48: 19–44.PubMedGoogle Scholar
  24. 24.
    Friedman RJ, Stemerman MB, Wenz B, Moore S, Gauldie J, Gent M, Tiell ML, Spaet TH (1977) The effect of thrombocytopenia on experimental arteriolsclerotic lesion formation in rabbit. J Clin Invest 60: 1191–1201.PubMedCrossRefGoogle Scholar
  25. 25.
    Fuster V, Chesebro JH (1986) Role of platelets and platelet inhibtors in aortocoronary artery vein-graft disease. Circulation 73: 227–232.PubMedCrossRefGoogle Scholar
  26. 26.
    Fuster V, Dewanjee MK, Kaye MP, Josa M, Metke MP, Chesebro JH (1979) Noninvasive radioisotopic technique for deterioration of platelet deposition in coronary artery bypass grafts in dogs and its reduction with platelet inhibitors. Circulation 60: 1508–1512.PubMedGoogle Scholar
  27. 27.
    Fuster V, Badimon L, Cohen M, Ambrose JA, Badimon JJ, Chesebro JH (1988) Insight into the pathogenesis of acute ischemic syndromes. Circulation 77: 1213–1220.PubMedCrossRefGoogle Scholar
  28. 28.
    Gortendorst G (1984) Alteration of the chemotactic response of NIH/3T3 cells to PDGF by growth factors, transformation and tumor promotors. Cell 36: 279–285.CrossRefGoogle Scholar
  29. 29.
    Grundfest WS, Litvack F, Sherman T, Carroll R, Lee M, Chaux A, Kass R, Matloff J, Berci G, Swan HJC, Morgenstern L, Forrester J (1985) Delineation of peripheral and coronary detail by intraoperative angioscopy. Ann Surg 202: 394–400.PubMedCrossRefGoogle Scholar
  30. 30.
    Hanson SR, Harker LA (1988) Interruption of acute platelet-dependent thrombosis by the synthetic antithrombin D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone. Proc Natl Acad Sci USA 85: 3184–3188.PubMedCrossRefGoogle Scholar
  31. 31.
    Harker LA, Harlan JM, Ross R (1983) Effect of sulfinpyrazone on homocystein-induced endothelial injury and arteriosclerosis. Circ Res 53: 731–739.PubMedGoogle Scholar
  32. 32.
    Haudenschild CC, Grunwald J (1985) Proliferative heterogeneity of vascular smooth muscle cells and its alteration by injury. Exp Cell Res 157: 364–370.PubMedCrossRefGoogle Scholar
  33. 33.
    Heras M, Chesbro JH, Penny WJ, Bailey KR, Badimon L, Fuster V (1989) Effects of thrombin inhibition on the development of acute platelet-thrombus deposit during angioplasty in pigs. Heparin vs. hirudin, a specific thrombin inhibitor. Circulation 79: 657–665.PubMedCrossRefGoogle Scholar
  34. 34.
    Hollman J, Schmidt A, von Bassewitz DB, Buddecke E (1989) Relationship of sulfated glycosaminoglycans and cholestrol content in normal and atherosclerotic human aorta. Arteriosclerosis 9: 154–158.CrossRefGoogle Scholar
  35. 35.
    Jang IK, Gold HK, Ziskind AA, Leinbach CR, Fallon JT, Collen D (1990) Prevention of platelet-rich arterial thrombosis by selective thrombin inhibition. Circulation 81: 219–225.PubMedCrossRefGoogle Scholar
  36. 36.
    Josa M, Lie JT, Bianco RL, Kaye MP (1981) Reduction of thrombosis in canine coronary bypass graft vein grafts with dipyridamole and aspirin Am J Cardiol 47: 1248–1254.PubMedCrossRefGoogle Scholar
  37. 37.
    Lie LT, Lawrie GM, Morris GC (1977) Aortocoronary bypass saphenous vein graft atherosclerosis. Am J Cardiol 40: 906–914.PubMedCrossRefGoogle Scholar
  38. 38.
    Lindner V, Lappi DA, Baird A, Majack RA, Reidy MA (1991) Role of basic fibroblast growth factor in lesion formation. Circ Res 68: 106–113.PubMedGoogle Scholar
  39. 39.
    LoGerfo FQ, Haudenschild CC, Quist WC (1984) A clinical technique for prevention of spasm and preservation of endothelium in saphenous vein grafts. Arch Surg 119: 1212–1214.PubMedCrossRefGoogle Scholar
  40. 40.
    Majesky MW, Reidy MA, Bowen-Pope DF, Hart CE, Wilcox JN, Schwartz SM (1990) PDGF ligand and receptor gene expression during repair of arterial injury. J Cell Biol 111: 2149–2158.PubMedCrossRefGoogle Scholar
  41. 41.
    Metke MP, Lie JT, Fuster V, Josa M, Kaye MP (1979) Reduction of intimal thickening in canine coronary bypass vein grafts with dipyridamole and aspirin. Am J Cardiol 43: 1144–1148.PubMedCrossRefGoogle Scholar
  42. 42.
    Peerschke EIB (1985) The platelet fibrinogen receptor. Semin Hematol 22: 241–259.PubMedGoogle Scholar
  43. 43.
    Raines EW, Dower SK, Ross R (1989) Interleukin-I mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science 243: 393–396.PubMedCrossRefGoogle Scholar
  44. 44.
    Reidy MA, Clowes AW, Schwartz SM (1983) Endothelial regeneration. V. Inhibition of endothelial regrowth in arteries of rat and rabbit. Lab Invest 49: 569–575.PubMedGoogle Scholar
  45. 45.
    Richardson M, Ihnatowycz I, Moore S (1980) Glycosaminoglycan distribution in rabbit aortic wall following balloon catheter deendothelialization: an ultrastructural study. Lab Invest 43: 509–516.PubMedGoogle Scholar
  46. 46.
    Ross R, Raines EW, Bowen-Pope DF (1986) The platelet derived growth factor. Cell 46: 155–169.PubMedCrossRefGoogle Scholar
  47. 47.
    Sakariassen KS, Nievelstein FF, Coller BS, Sixma JJ (1986) The role of platelet membrane glycoprotein Ib and IIb/IIIa is platelet adherence to human artery subendothelium. Br J Haematol 63: 681–691.PubMedCrossRefGoogle Scholar
  48. 48.
    Schwartz SM, Reidy MA (1987) Common mechanism of proliferation of smooth muscle in atherosclerosis and hypertension. Hum Pathol 18: 240–247.PubMedCrossRefGoogle Scholar
  49. 49.
    Schwartz CJ, Valente AJ, Kelly JL, Sprague EA, Edwards EH (1988) Thrombosis and the development of atherosclerosis: Rokitansky revisited. Semin Thromb Hemost 14: 189–194.PubMedCrossRefGoogle Scholar
  50. 50.
    Senior RM, Griffin GL, San Huang J, Walz AA, Deuel TF (1983) Chemotactic activity of platelet alpha granule proteins for fibroblast. J Cell Biol 96: 382–385.PubMedCrossRefGoogle Scholar
  51. 51.
    Shuman MA (1986) Thrombin-cellular interactions. Ann NY Acad Sci 485: 288–289.CrossRefGoogle Scholar
  52. 52.
    Snow AD, Bolender RP, Wright TN, Clowes AW (1990) Heparin modulates the composition of the extracellular matrix domain surrounding arterial smooth muscle cells. Am J Pathol 137: 313–330.PubMedGoogle Scholar
  53. 53.
    Turitto VT, Weiss JH, Baumgartner HR (1984) Platelet interaction with rabbit subendothelium in von Willebrand’s disease: altered thrombus formation distinct from defective platelet adhesion. J Clin Invest 74: 1730–1741.PubMedCrossRefGoogle Scholar
  54. 54.
    Uni KK, Kottke BA, Titus JL, Frye RL, Wallace RB, Brown AL (1974) Pathologic changes in aortocoronary saphenous vein grafts. Am J Cardiol 34: 526–532.CrossRefGoogle Scholar
  55. 55.
    Walker LN, Ramsey MM, Bowyer DE (1983) Endothelial healing following defined injury to rabbit aorta: depth of injury and mode of repair. Atherosclerosis 47: 123–130.PubMedCrossRefGoogle Scholar
  56. 56.
    Walker LN, Bowen-Pope DF, Ross R, Reidy MA (1986) Production of platelet-derived growth factor-like molecule by cultured arterial smooth muscle cells accompanied proliferation after arterial injury. Proc Natl Acad Sci USA 83: 7311–7315.PubMedCrossRefGoogle Scholar
  57. 57.
    Weiss HJ, Turitto VT, Baumgartner HR (1978) Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. I. Shear rate-dependent decrease of adhesion in von Willebrand’s disease and the Bernard-Soulier syndrome. J Lab Clin Med 92: 750–754.PubMedGoogle Scholar
  58. 58.
    Wight LN (1989) Cell biology of arterial proteoglycans. Arteriosclerosis 9: 1–20.PubMedCrossRefGoogle Scholar
  59. 59.
    Yea-Herttuala S, Sumuvuori H, Karkola K, Mottonen M, Nikkari P (1986) Glycosaminoglycans in normal and atherosclerotic human coronary arteries. Lab Invest 54: 402–408.Google Scholar

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© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • I. K. Jang
  • V. Fuster

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