Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation

Department of Medicine, Mount Sinai Medical Center, New York, New York 10029-6574.

Vascular injury represents a critical initiating event in the pathogenesis of various vascular diseases, including atherosclerosis. This review discusses 1) the current understanding and a new pathologic classification of vascular injury; 2) the resultant cellular pathophysiologic responses, specifically, lipid accumulation, platelet aggregation, thrombus formation and smooth muscle cell proliferation; 3) the role of vascular injury in the pathogenesis of spontaneous and accelerated atherosclerosis; and 4) emerging therapeutic approaches in preventing these vascular diseases. The process of type I vascular injury (nondenuding functional injury) followed by lipid accumulation, monocyte and platelet adhesion, smooth muscle cell proliferation and resultant plaque formation represents the prevalent view of the early stages of spontaneous atherogenesis. The syndromes of accelerated atherosclerosis (namely, heart transplant atherosclerosis, coronary vein graft disease and restenosis after percutaneous transluminal coronary angioplasty) appear to share etiologic mechanisms with spontaneous atherosclerosis by means of the "response to injury" hypothesis. However, type II and type III vascular injury (denuding endothelial and intimal injury with or without medial damage) followed by thrombus and its organization by smooth muscle cell proliferation and subsequent fibrosis appear to be responsible for the vascular process. This accelerated and premature occlusive process accounts for significant morbidity and mortality in patients with these conditions. Better understanding of the nature of vascular injury and its pathophysiologic responses in these clinical situations may aid in developing therapeutic strategies for preventing these vascular diseases.

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				D. Mulcahy, S. Husain, G. Zalos, A. Rehman, N. P. Andrews, W. H. Schenke, N. L. Geller, and A. A. Quyyumi Ischemia During Ambulatory Monitoring as a Prognostic Indicator in Patients With Stable Coronary Artery Disease JAMA, January 22, 1997; 277(4): 318 - 324. [Abstract] [PDF]

				J. L. West and J. A. Hubbell Separation of the arterial wall from blood contact using hydrogel barriers reduces intimal thickening after balloon injury in the rat: The roles of medial and luminal factors in arterial healing PNAS, November 12, 1996; 93(23): 13188 - 13193. [Abstract] [Full Text] [PDF]

				D. F. Lazarous, M. Shou, M. Scheinowitz, E. Hodge, V. Thirumurti, A. N. Kitsiou, J. A. Stiber, A. D. Lobo, S. Hunsberger, E. Guetta, et al. Comparative Effects of Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor on Coronary Collateral Development and the Arterial Response to Injury Circulation, September 1, 1996; 94(5): 1074 - 1082. [Abstract] [Full Text]

				M. Ragosta, W. L. Barry, L. W. Gimple, S. D. Gertz, K. W. McCoy, G. A. Stouffer, C. A. McNamara, E. R. Powers, G. K. Owens, and I. J. Sarembock Effect of Thrombin Inhibition With Desulfatohirudin on Early Kinetics of Cellular Proliferation After Balloon Angioplasty in Atherosclerotic Rabbits Circulation, March 15, 1996; 93(6): 1194 - 1200. [Abstract] [Full Text]

				S. Oho, S. J. Daley, E. W.Y. Koo, T. Childs, A. I. Gotlieb, and M. Rabinovitch Increased Elastin-Degrading Activity and Neointimal Formation in Porcine Aortic Organ Culture : Reduction of Both Features With a Serine Proteinase Inhibitor Arterioscler Thromb Vasc Biol, December 1, 1995; 15(12): 2200 - 2206. [Abstract] [Full Text]

				C. M. Speidel, P. R. Eisenberg, W. Ruf, T. S. Edgington, and D. R. Abendschein Tissue Factor Mediates Prolonged Procoagulant Activity on the Luminal Surface of Balloon-Injured Aortas in Rabbits Circulation, December 1, 1995; 92(11): 3323 - 3330. [Abstract] [Full Text]

				M. Pasic, W. Muller-Glauser, B. Odermatt, M. Lachat, B. Seifert, and M. Turina Seeding With Omental Cells Prevents Late Neointimal Hyperplasia in Small-Diameter Dacron Grafts Circulation, November 1, 1995; 92(9): 2605 - 2616. [Abstract] [Full Text]

				C. Hehrlein, C. Gollan, K. Donges, J. Metz, R. Riessen, P. Fehsenfeld, E. von Hodenberg, and W. Kubler Low-Dose Radioactive Endovascular Stents Prevent Smooth Muscle Cell Proliferation and Neointimal Hyperplasia in Rabbits Circulation, September 15, 1995; 92(6): 1570 - 1575. [Abstract] [Full Text]

				Y.-Y. Fan, K. S. Ramos, and R. S. Chapkin Dietary {gamma}-Linolenic Acid Modulates Macrophage Vascular Smooth Muscle Cell Interactions : Evidence for a Macrophage-Derived Soluble Factor That Downregulates DNA Synthesis in Smooth Muscle Cells Arterioscler Thromb Vasc Biol, September 1, 1995; 15(9): 1397 - 1403. [Abstract] [Full Text]

				C. J. Pastore, J. M. Isner, P. A. Bacha, M. Kearney, and J. G. Pickering Epidermal Growth Factor Receptor Targeted Cytotoxin Inhibits Neointimal Hyperplasia In Vivo : Results of Local Versus Systemic Administration Circ. Res., September 1, 1995; 77(3): 519 - 529. [Abstract] [Full Text]

				A. I. Fyfe, A. Rosenthal, and A. I. Gotlieb Immunosuppressive Agents and Endothelial Repair : Prednisolone Delays Migration and Cytoskeletal Rearrangement in Wounded Porcine Aortic Monolayers Arterioscler Thromb Vasc Biol, August 1, 1995; 15(8): 1166 - 1171. [Abstract] [Full Text]

				G. Montalescot, A. Ankri, E. Vicaut, G. Drobinski, Y. Grosgogeat, and D. Thomas Fibrinogen After Coronary Angioplasty as a Risk Factor for Restenosis Circulation, July 1, 1995; 92(1): 31 - 38. [Abstract] [Full Text]

				R. L. Geary, N. Koyama, T. W. Wang, S. Vergel, and A. W. Clowes Failure of Heparin to Inhibit Intimal Hyperplasia in Injured Baboon Arteries : The Role of Heparin-Sensitive and -Insensitive Pathways in the Stimulation of Smooth Muscle Cell Migration and Proliferation Circulation, June 15, 1995; 91(12): 2972 - 2981. [Abstract] [Full Text]

				J. Escaned and P. W. Serruys Presence of Thrombosis in Coronary Atherosclerotic Plaques European Journal of Cardiovascular Prevention & Rehabilitation, June 1, 1995; 2(3): 189 - 196. [Abstract] [PDF]

				E. M. Tuzcu, R. E. Hobbs, G. Rincon, C. Bott-Silverman, A. C. De Franco, K. Robinson, P. M. McCarthy, R. W. Stewart, S. Guyer, and S. E. Nissen Occult and Frequent Transmission of Atherosclerotic Coronary Disease With Cardiac Transplantation : Insights From Intravascular Ultrasound Circulation, March 15, 1995; 91(6): 1706 - 1713. [Abstract] [Full Text]

				A. Corsini, D. Verri, M. Raiteri, P. Quarato, R. Paoletti, and R. Fumagalli Effects of 26-Aminocholesterol, 27-Hydroxycholesterol, and 25-Hydroxycholesterol on Proliferation and Cholesterol Homeostasis in Arterial Myocytes Arterioscler Thromb Vasc Biol, March 1, 1995; 15(3): 420 - 428. [Abstract] [Full Text]

				E. R. Edelman, M. Simons, M. G. Sirois, and R. D. Rosenberg c-myc in Vasculoproliferative Disease Circ. Res., February 1, 1995; 76(2): 176 - 182. [Abstract] [Full Text]