Remodeling: How Vessels Narrow

  • Stephen M. Schwartz


Vascular narrowing is the fundamental defect characterizing atherosclerosis and hypertension. This loss of physiological caliber occurs despite the remarkable ability of normal vessels to maintain the caliber appropriate for the blood flow needed for the subservient organ. Indeed, the ability to adjust caliber must be very primitive. The vessel tree, like any closed circuit, can only continue to conduct blood if each branch has an appropriate resistance to flow. Flow, moreover, is proportional to the fourth power of the radius. Thus, the normal vessel wall must and does have an exquisite mechanism for controlling lumen size.


Smooth Muscle Cell Tissue Factor Neointimal Hyperplasia Neointimal Formation Arterial Smooth Muscle Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    O’Brien ER, Alpers CE, Stewart DK, Ferguson M, Tran N, Gordon D, Benditt EP, Hinohara T, Simpson JB, Schwartz SM (1993) Proliferation in primary and restenotic coronary atherectomy tissue: implications for antiproliferative therapy. Circ Res 73: 223–231PubMedCrossRefGoogle Scholar
  2. 2.
    Mintz GS, Douek PC, Bonner RF, Kent KM, Pichard AD, Satier LF, Leon MB (1993) Intravascular ultrasound comparison of de novo and restenotic coronary artery lesions (abstract). J Am Coll Cardiol 21: 118AGoogle Scholar
  3. 3.
    Schwartz SM, Murry CD, O’Brien ER (1996) Vessel wall response to injury. Sci Am Sci Med Mar/Apr: 12–21Google Scholar
  4. 4.
    Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ (1987) Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 316: 13711375Google Scholar
  5. 5.
    Clarkson TB, Prichard RW, Morgan TM, Petrick GS, Klein KP (1994) Remodeling of coronary arteries in human and nonhuman primates. JAMA 271 (4): 289–294PubMedCrossRefGoogle Scholar
  6. 6.
    Dussaillant GR, Mintz GS, Pichard AD, Kent KM, Satter LF, Popma JJ, Wong SC, Leon MB (1995) Small stent size and intimai hyperplasia contribute to restenosis: a volumetric intravascular ultrasound analysis. J Am Coll Cardiol 26 (3): 720–724PubMedCrossRefGoogle Scholar
  7. 7.
    Noden DM (1989) Embryonic origins and assembly of blood vessels. Am Rev Respir Dis 140: 1097–1103PubMedGoogle Scholar
  8. 8.
    Coffin JD, Harrison J, Schwartz SM, Heimark R (1991) Angioblast differentiation and morphogenesis of the vascular endothelium in the mouse embryo. Dev Biol 148: 51–62PubMedCrossRefGoogle Scholar
  9. 9.
    Fishman MC, Stainier DY (1994) Cardiovascular development. Prospects for a genetic approach. Circ Res 74 (5): 757–763PubMedCrossRefGoogle Scholar
  10. 10.
    Dilley RJ, Schwartz SM (1989) Vascular remodeling in the growth hormone transgenic mouse. Circ Res 65: 1223–1240CrossRefGoogle Scholar
  11. 11.
    Majesky MW, Topouzis S (1995) Smooth muscle lineage diversity and atherosclerosis. Atherosclerosis 10: 56Google Scholar
  12. 12.
    Pardanaud L, Yassine F, Dieterlen-Lievre F (1989) Relationship between vasculogenesis, angiogenesis and haemopoiesis during avian ontogeny. Development (Camb) 105: 473–485Google Scholar
  13. 13.
    Rosenquist TH, McCoy JR, Waldo KL, Kirby ML (1988) Origin and propagation of elastogenesis in the developing cardiovascular system. Anat Rec 221: 860–871PubMedCrossRefGoogle Scholar
  14. 14.
    Majesky MW, Giachelli CM, Schwartz SM (1992) Rat carotid neointimal smooth muscle cells re-express a developmentally regulated phenotype during repair of arterial injury. Circ Res 71: 759–768PubMedCrossRefGoogle Scholar
  15. 15.
    Wunsch AM, Little CD, Markwald RR (1994) Cardiac endothelial heterogeneity defines valvular development as demonstrated by the diverse expression of JB3, an antigen of the endocardial cushion tissue. Dev Biol 165: 585–601PubMedCrossRefGoogle Scholar
  16. 16.
    Bobryshev YV, Lord RS (1995) Ultrastructural recognition of cells with dendritic cell morphology in human aortic intima. Contacting interactions of vascular dendritic cells in athero-resistant and athero-prone areas of the normal aorta. Arch Histol Cytol 58 (3): 307–322PubMedCrossRefGoogle Scholar
  17. 17.
    Langille BL, O’Donnell F (1986) Reductions in arterial diameter produced by chronic diseases in blood flow are endothelium-dependent. Science 231: 405–407PubMedCrossRefGoogle Scholar
  18. 18.
    Folkow B (1982) Physiological aspects of primary hypertension. Physiol Rev 62: 347–504PubMedGoogle Scholar
  19. 19.
    Heagerty AM, Aalkjaer C, Bund SJ, Korsgaard N, Mulvany MJ (1993) Small artery structure in hypertension. Dual processes of remodeling and growth. Hypertension 21: 391–397Google Scholar
  20. 20.
    Alkjaer C, Heagerty AM, Mulvany MJ (1987) In vitro characteristics of vessels from patients with essential hypertension. J Clin Hypertens 3: 317–322Google Scholar
  21. 21.
    Korsgaard N, Aalkjaer C, Heagerty AM, Izzard AS, Mulvany MJ (1993) Histology of subcutaneous small arteries from patients with essential hypertension. Hypertension (Dallas) 22: 523–526CrossRefGoogle Scholar
  22. 22.
    Albelda SM, Oliver PD, Romer LH, Buck CA, Endo CAM (1990) A novel endothelial cell-cell adhesion molecule. J Cell Biol 110: 1227–1237PubMedCrossRefGoogle Scholar
  23. 23.
    Gage AA, Fazekas C, Riley EE (1967) Freezing injury to large blood vessels in dogs. Surgery (St Louis) 61: 748–754Google Scholar
  24. 24.
    Bjorkerud S, Bondjers G (1971) Arterial repair and atherosclerosis after mechanical injury. Part 2. Tissue response after induction of a large superficial necrosis (deep longitudinal injury). Atherosclerosis 14: 259–276Google Scholar
  25. 25.
    Poole JCF, Cromwell SB, Benditt EP (1971) Behavior of smooth muscle cells and formation of extracellular structures in the reaction of arterial walls to injury. Am J Pathol 62: 391–414PubMedGoogle Scholar
  26. 26.
    Haudenschild CC, Prescott MF, Chobanian AV (1980) Effects of hypertension and its reversal on aortic lesions of the rat. Hypertension (Dallas) 2: 33–44CrossRefGoogle Scholar
  27. 27.
    Velican D, Velican C (1976) Intimal thickening in developing coronary arteries and its relevance to atherosclerotic involvement. Atherosclerosis 23: 345CrossRefGoogle Scholar
  28. 28.
    Velican C, Velican D (1980) The precursors of coronary atherosclerotic plaques in subjects up to 40 years old. Atherosclerosis 37: 33–46PubMedCrossRefGoogle Scholar
  29. 29.
    Sims FH, Gavin JB, Vanderwee MA (1989) The intima of human coronary arteries. Am Heart J 118: 32–38PubMedCrossRefGoogle Scholar
  30. 30.
    Hatton MW, Moar SL, Richardson M (1989) De-endothelialization in vivo initiates a thrombogenic reaction at the rabbit aorta surface. Am J Pathol 135: 499–508PubMedGoogle Scholar
  31. 31.
    Clowes AW, Clowes MM, Reidy MA (1983) Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. Lab Invest 49: 327–333Google Scholar
  32. 32.
    Schwartz SM, Heimark RL, Majesky MW (1990) Developmental mechanisms underlying pathology of arteries. Physiol Rev 70: 1177–1209PubMedGoogle Scholar
  33. 33.
    Ross R (1986) The pathogenesis of atherosclerosis—an update. N Engl J Med 314: 488500Google Scholar
  34. 34.
    Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362: 801–809PubMedCrossRefGoogle Scholar
  35. 35.
    Jorgensen L, Grothe AG, Groves HM, Kinlough-Rathbone RL, Richardson M, Mustard JF (1988) Sequence of cellular responses in rabbit aortas following one and two injuries with a balloon catheter. Br J Exp Pathol 69: 473–486PubMedGoogle Scholar
  36. 36.
    Fingerle J, Johnson R, Clowes AW, Majesky MW, Reidy MA (1989) Role of platelets in smooth muscle cell proliferation and migration after vascular injury in rat carotid artery. Proc Natl Acad Sci USA 86: 8412–8416PubMedCrossRefGoogle Scholar
  37. 37.
    Jackson CL, Raines EW, Ross R, Reidy MA (1993) Role of endogenous platelet-derived growth factor in arterial smooth muscle cell migration after balloon catheter injury. Arterioscler Thromb 13: 1218–1226PubMedCrossRefGoogle Scholar
  38. 38.
    Jawien A, Bowen-Pope DF, Lindner V, Schwartz SM, Clowes AW (1992) Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty. J Clin Invest 89: 507–511PubMedCrossRefGoogle Scholar
  39. 39.
    Majesky MW, Reidy MA, Bowen-Pope DF, Wilcox JN, Schwartz SM (1990) Platelet-derived growth factor ( PDGF) ligand and receptor gene expression during repair of arterial injury. J Cell Biol 111: 2149–2158Google Scholar
  40. 40.
    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: 3739–3743PubMedCrossRefGoogle Scholar
  41. 41.
    Prescott M, Webb R, Reidy MA (1991) Angiotensin-converting enzyme inhibitors versus angiotensin II, AT1 receptor antagonist: effects on smooth muscle cell migration and proliferation after balloon catheter injury. Am J Pathol 139: 1291–1296PubMedGoogle Scholar
  42. 42.
    Bennett MR, Schwartz SM (1995) Antisense therapy for angioplasty restenosis—some critical considerations. Circulation 92: 1981–1993PubMedCrossRefGoogle Scholar
  43. 43.
    Clowes AW, Schwartz SM (1985) Significance of quiescent smooth muscle migration in the injured rat carotid artery. Circ Res 56: 139–145PubMedCrossRefGoogle Scholar
  44. 44.
    Grotendorst GR, Seppa HEJ, Kleinman HK, Martin GR (1981) Attachment of smooth muscle cells to collagen and their migration toward platelet-derived growth factor. Proc Natl Acad Sci USA 78: 3669–3672PubMedCrossRefGoogle Scholar
  45. 45.
    Schwartz SM, Stemerman MB, Benditt EP (1975) The aortic intima. II. Repair of the aortic lining after mechanical denudation. Am J Pathol 81: 15–42Google Scholar
  46. 46.
    Daemen MJAP, Lombardi DM, Bosman FT, Schwartz SM (1991) Angiotensin II induces smooth muscle cell proliferation in the normal and injured arterial wall. Circ Res 68: 450–456PubMedCrossRefGoogle Scholar
  47. 47.
    Powell J, Clozel J, Muller R (1989) Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury. Science 245: 186–188PubMedCrossRefGoogle Scholar
  48. 48.
    Benditt EP, Benditt JM (1973) Evidence for a monoclonal origin of human atherosclerotic plaques. Proc Natl Acad Sci USA 70: 1753–1756PubMedCrossRefGoogle Scholar
  49. 49.
    Lee KT, Thomas WA, Florentin RA, Reiner JM, Lee WM (1976) Evidence for a polyclonal origin and proliferation heterogeneity of atherosclerotic lesions induced by dietary cholesterol in swine. Ann NY Acad Sci 275: 336–347PubMedCrossRefGoogle Scholar
  50. 50.
    Thomas WA, Kim DN (1983) Biology of disease: atherosclerosis as a hyperplastic and/ or neoplastic process. Lab Invest 48: 245–255PubMedGoogle Scholar
  51. 51.
    Janakidevi K, Lee KT, Kroms M, Imai H, Thomas WA (1984) Mosaicism in female hybrid hares heterozygous for glucose-6-phosphate-dehydrogenase. VI. Production of monotypism in the arotas of four of 10 mosaic hares fed cholesterol oxidation products. Exp Mol Pathol 41: 354–362PubMedCrossRefGoogle Scholar
  52. 52.
    Taubman MB (1993) tissue factor regulation in vascular smooth muscle: a summary of studies performed using in vivo and in vitro models. Am J Cardiol 72:55C–60CGoogle Scholar
  53. 53.
    Fuster V, Badimon JJ, Badimon L (1992) Clinical-pathological correlations of coronary disease progression and regression. Circulation 86:Aí1-II111Google Scholar
  54. 54.
    Fuster V, Badimon L, Badimon J, Chesebro JH (1992) The pathogenesis of coronary artery disease and the acute coronary syndromes (1). N Engl J Med 326: 242–250PubMedCrossRefGoogle Scholar
  55. 55.
    Fuster V, Badimon L, Badimon J, Chesebro JH (1992) The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 326: 310–318PubMedCrossRefGoogle Scholar
  56. 56.
    Landers SC, Gupta M, Lewis JC (1994) Ultrastructural localization of tissue factor on monocyte-derived macrophages and macrophage foam cells associated with atherosclerotic lesions. Virchows Arch 425: 49–54PubMedCrossRefGoogle Scholar
  57. 57.
    Brand K, Banka CL, Mackman N, Terkeltaub RA, Fan ST, Curtiss LK (1994) Oxidized LDL enhances lipopolysaccharide-induced tissue factor expression in human adherent monocytes. Arterioscler Thromb 14: 790–797PubMedCrossRefGoogle Scholar
  58. 58.
    Wilcox JN, Smith KM, Schwartz SM, Gordon D (1989) Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 86: 2839–2843PubMedCrossRefGoogle Scholar
  59. 59.
    Reidy MA (1985) A reassessment of endothelial injury and arterial lesion formation. Lab Invest 53: 513–520PubMedGoogle Scholar
  60. 60.
    Drake TA, Morrissey JH, Edgington TS (1989) Selective cellular expression of tissue factor in human tissues. Am J Pathol 134: 1087–1097PubMedGoogle Scholar
  61. 61.
    Kuntz RE, Gibson M, Nobuyoshi M, Bairn DS (1993) Generalized model of restenosis after conventional balloon angioplasty stenting and directional atherectomy. J Am Coll Cardiol 21: 15–25PubMedCrossRefGoogle Scholar
  62. 62.
    Lawn RM, Wade DP, Hammer RE, Chiesa G, Verstuyft JG, Rubin EM (1992) Atherogenesis in transgenic mice expressing human apolipoprotein(a). Nature 360: 670–672PubMedCrossRefGoogle Scholar
  63. 63.
    Schwartz SM, deBlois D, O’Brien ER (1995) The intima: soil for atherosclerosis and restenosis. Circ Res 77: 445–465PubMedCrossRefGoogle Scholar
  64. 64.
    Majesky MW, Benditt EP, Schwartz SM (1988) Expression and developmental control of platelet-derived growth factor A-chain and B-chain/sis genes in rat aortic smooth muscle cells. Proc Natl Acad Sci USA 85: 1524–1528PubMedCrossRefGoogle Scholar
  65. 65.
    Seifert RA, Schwartz SM, Bowen-Pope DF (1984) Developmentally regulated production of platelet-derived growth factor-like molecules. Nature 311: 669–671PubMedCrossRefGoogle Scholar
  66. 66.
    Lemire JM, Covin CW, White S, Giachelli CM, Schwartz SM (1994) Characterization of cloned aortic smooth muscle cells from young rats. Am J Pathol 144: 1068–1081PubMedGoogle Scholar
  67. 67.
    Walker L, Bowen-Pope DF, Ross R, Reidy MA (1986) Production of PDGF-like molecules by cultured arterial smooth muscle cells accompanies proliferation after arterial injury. Proc Natl Acad Sci USA 83: 7311–7315PubMedCrossRefGoogle Scholar
  68. 68.
    Sjolund M, Hedin U, Sejersen R, Heldin CH, Thyberg J (1988) Arterial smooth muscle cells express PDGF-A chain mRNA, secrete a PDGF-like mitogen, and bind exogenous PDGF in a phenotype-and growth state-dependent manner. J Cell Biol 106: 403–413PubMedCrossRefGoogle Scholar
  69. 69.
    Lindner V, Reidy MA (1995) Platelet-derived growth factor ligand and receptor expression by large vessel endothelium in vivo. Am J Pathol 146: 1488–1497PubMedGoogle Scholar
  70. 70.
    Moss NS, Benditt EP (1975) Human atherosclerotic plaque cells and leiomyoma cells: comparison of in vitro growth characteristics. Am J Pathol 78: 175–190PubMedGoogle Scholar
  71. 71.
    Bennett MR, Evan GI, Schwartz SM (1995) Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J Clin Invest 95: 2266–2274PubMedCrossRefGoogle Scholar
  72. 72.
    Jamal A, Bendeck M, Langille BL (1992) Structural changes and recovery of function after arterial injury. Arterioscler Thromb 12: 307–317PubMedCrossRefGoogle Scholar
  73. 73.
    O’Brien ER, Alpers CE, Stewart DK, Ferguson M, Tran N, Gordon D, Benditt EP, Hinohara T, Simpson JB, Schwartz SM (1993) Proliferation in primary and restenotic coronary atherectomy tissue: implications for antiproliferative therapy. Circ Res 73: 223–231PubMedCrossRefGoogle Scholar
  74. 74.
    Mintz GS, Douek PC, Bonner RF (1993) Intravascular ultrasound comparison of de novo and restenotic coronary artery lesions. J Am Coll Cardiol 21: 118AGoogle Scholar
  75. 75.
    Arbustini E, Grasso M, Diegoli M, Pucci A, Bramerio M, Ardissino D, Angoli L, de Servi S, Bramucci E, Mussini A (1991) Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. Am J Cardiol 68: 36B - 50BPubMedCrossRefGoogle Scholar
  76. 76.
    Davies MJ (1992) Anatomic features in victims of sudden coronary death. Coronary artery pathology. Circulation 85 (suppl 1): 119–124Google Scholar

Copyright information

© Springer Japan 1997

Authors and Affiliations

  • Stephen M. Schwartz
    • 1
  1. 1.Department of PathologyUniversity of WashingtonSeattleUSA

Personalised recommendations