The Role of Blood and Platelets in Atherosclerosis and the Complications of Atherosclerosis^[*]

Summary

There appear to be at least three ways in which the blood, and particularly the platelets, may contribute to the development of atherosclerosis and its complications :

1. In the mechanism causing endothelial injury and the response of the smooth muscle cells to vessel injury.

2. Through the formation of persistent mural thrombi which are organized into intimai thickenings.

3. Through the formation of thrombi in association with advanced atherosclerosis that may be either (a) mural thrombi which fragment and shower the distal circulation with platelet emboli or (b) occlusive thrombi.

^* Presented at the National Conference on Thrombosis and Hemostatis, under the auspices of the Council on Thrombosis of the American Heart Association, Dallas, Texas, November 1974.

• References

• 1 Baumgaetner H. R. The subendothelial surface and thrombosis. Thrombosis et Diathesis Haemorrhagica 1974; 59 Supplement 91
• 2 Björkerud S, Bondjers G. Arterial repair and atherosclerosis after mechan- ical injury. Part 5. Tissue response after induction of a large superficial transverse injury. Atherosclerosis 1973; 18: 235
• 3 Burch G. E. Viruses and arteriosclerosis. American Heart Journal 1974; 87: 407
• 4 Caplan B. A, Schwartz C. J. Increased endothelial cell turnover in areas of in vivo Evans blue uptake in the pig aorta. Atherosclerosis 1973; 17: 401
• 5 Caro C. G, Fitz-Gerald J. M, Schroter R. C. Atheroma and arterial wall shear: Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis. Proceedings of the Royal Society of London B 1971; 177: 109
• 6 Chandler A. B. Thrombosis and the development of atherosclerotic lesions. In Jones R. J. (ed.) Atherosclerosis . New York: Springer-Verlag; 88 1970
• 7 Clark E, Graef I, Chasis H. Thrombosis of the aorta and coronary arteries. With special reference to the “fibrinoid” lesions. Archives of Pathology 1936; 22: 183
• 8 Constantinides P. Experimental production of atherosclerosis through injury. In Constantinides P. (ed.) Experimental Atherosclerosis . Amsterdam: Elsevier Publishing Co.,; 1965: 49
• 9 Dalldore F. G, Pate D. H, Langdell R. D. Pulmonary capillary thrombosis in experimental pneumococcal septicemia. Archives of Pathology 1968; 85: 149
• 10 Davies D. P, Johnson A. P, Rees B. W. G, Elwood P. C, Abernethy M. Food antibodies and myocardial infarction. Lancet 1974; 1: 1012
• 11 Duguid J. B. Thrombosis as a factor in the pathogenesis of aortic atherosclerosis. Journal of Pathology and Bacteriology 1948; 60: 57
• 12 Fisher C. M. Observations of the fundus oculi in transient monocular blindness. Neurology (Minneap.) 1959; 9: 333
• 13 French J. E. Atherosclerosis in relation to the structure and function of the arterial intima with special reference to the endothelium. International Review of Experimental Pathology 1966; 5: 253
• 14 Friedman R. J, Moore S, Singal D. P. Repeated endothelial injury and induction of atherosclerosis in normolipemic rabbits by human serum. Laboratory Investigation (In Press). 1975
• 15 Fry D. L. Certain chemorheological considerations regarding the blood vascular interface with particular reference to coronary artery disease. Circulation 1969; to volumes 39 (Suppl. 04) Supplement (40) 38
• 16 Gaynor E, Bouvier C. A, Spaet T. H. Vascular lesions: possible pathogenetic basis of the generalized Shwartzman reaction. Science 1970; 170: 986
• 17 Geer J. C, Haust M. D. In Pollak O. J, Simms H. S, Kirk J. E. (eds.) Smooth Muscle Cells in Atherosclerosis Monographs on Atherosclerosis. Volume 2. New York: Karger; 1972
• 18 Goldsmith H. L. The flow of model particles and blood cells and it relation to thrombogenesis. In Spaet T. H. (ed.) Progress in Hemostasis and Thrombosis, Volume 1. New York: Grune and Stratton; 1972: 97
• 19 Gunning A. J, Pickering G. W, Robb-Smith A. H. T, Russell R. R. Mural thrombosis of the internal carotid artery and subsequent embolism. Quarterly Journal of Medicine (N.S.) 1964; 33: 155
• 20 Gutstein W. H, Farrell G. A, Armellini C. Blood flow disturbance and endothelial cell injury in preatherosclerotic swine. Laboratory Investigation 1973; 29: 134
• 21 Haerem J. W. Sudden coronary death: the occurrence of platelet aggregates in the epicardial arteries of man. Atherosclerosis 1971; 14: 417
• 22 Haerem J. W. Platelet aggregates in intramyocardial vessels of patients dying suddenly and unexpectedly of coronary artery disease. Atherosclerosis 1972; 15: 199
• 23 Haerem J. W. Mural platelet microthrombi and major acute lesions of main epicardial arteries in sudden coronary death. Atherosclerosis 1974; 19: 529
• 24 Hardin N. J, Minick C. R, Murphy G. E. Experimental induction of atheroarteriosclerosis by the synergy of allergic injury to arteries and lipidrich diet. III. The role of earlier acquired fibromuscular intimai thickening in the pathogenesis of later developing atherosclerosis. American Journal of Pathology 1973; 73: 301
• 25 Harker L. A, Slighter S. J, Scott C. R, Ross R. Homocystinemia: vascular injury and arterial thrombosis. New England Journal of Medicine 1974; 291: 537
• 26 Hass G. M, Trueheart R. E, Hemmens A. Experimental athero-arterio- sclerosis due to calcific medial degeneration and hypercholesteremia. American Journal of pathology 1961; 38: 289
• 27 Haust M. D. Injury and repair in the pathogenesis of atherosclerotic lesions. In Jones R. J. (ed.) Atherosclerosis . New York: Springer-Verlag; 1970: 12
• 28 Haust M. D, More R. H. Development of modern theories on the pathogenesis of atherosclerosis. In Wissler R. W, Geer J. C. (eds.) The Pathogenesis of Atherosclerosis . Baltimore: Williams and Wilkins; 1 1972
• 29 Hovig T. Release of platelet-aggregating substance (adenosine diphosphate) from rabbit blood platelets induced by saline “extract” of tendons. Thrombosis et Diathesis Haemorrhagica 1963; 9: 264
• 30 Hughes A, Tonks R. S. The role of microemboli in the production of carditis in hypersensitivity experiments. Journal of Pathology and Bacteriology 1959; 77: 207
• 31 Jørgensen L, Haeeem J. W, Chandlbr A. B, Borchgrevink C. F. The pathology of acute coronary death. Acta Anaesthesiologica Scandinavica Supplement 29: 193 1968;
• 32 Jørgensen L, Hovig T, Rowsell H. C, Mustard J. F. Adenosine diphosphateinduced platelet aggregation and vascular injury in swine and rabbits. American Journal of Pathology 1970; 61: 161
• 33 Jørgensen L, Packham M. A, Rowsell H. C, Mustard J. F. Deposition of formed elements of blood on the intima and signs of intimai injury in the aorta of rabbit, pig and man. Laboratory Investigation 1972; 27: 341
• 34 Jørgensen L, Rowsell H.C, Hovig T, Glynn M. F, Mustard J. F. Adenosine diphosphateinduced platelet aggregation and myocardial infarction in swine. Laboratory Investigation 1967; 17: 616
• 35 Jørgensen L, Rowsell H.C, Hovig T, Mustard J. F. Resolution and organization of plateletrich mural thrombi in carotid arteries of swine. American Journal of Pathology 51: 681 1967;
• 36 Kniker W. T, Cochrane C. G. The localization of circulating immune complexes in experimental serum sickness. The role of vasoactive amines and hydrodynamic forces. Journal of Experimental Medicine 1968; 127: 119
• 37 Kohler N, Lipton A. Platelets as a source of fibroblast growth-promoting activity. Experimental Cell Research 1974; 87: 297
• 38 LePow I. H, Dias da Silva W, Patrick R. A. Biologically active cleavage products of components of complement. In Movat H. Z. (ed.) Cellular and Humoral Mechanisms in Anaphylaxis and Allergy . Karger: New York; 1969: 237
• 39 Magnani B, Coccheri S. The pathogenesis of dietetic atheromasia in the rabbit : significance of phenomena of changed vascular permeability. Giornale di Clinica Medica 1960; 41: 1103
• 40 Moore S. The relation of superficial cortical scars of the kidney to aortic atherosclerosis; a hypothesis of renal ischemia. Journal of Pathology and Bacteriology 1964; 88: 471
• 41 Moore S. Hypertension and renal ischemia. Geriatrics 1969; 24: 81
• 42 Moore S. Thromboatherosclerosis in normolipemic rabbits: a result of continued endothelial damage. Laboratory Investigation 1973; 29: 478
• 43 Moore S, Gent M. Plasma renin activity in experimental nephrosclerosis and hypertension. Circulation 46 Supplement (Suppl. 02) 70 1972;
• 44 Moore S, Lough J. Lipid accumulation in renal arterioles due to platelet aggregate embolism. American Journal of Pathology 1970; 58: 283
• 45 Moore S, Mersereau W. A. Microembolic renal ischemia, hypertension and nephrosclerosis. Archives of Pathology 1968; 85: 623
• 46 Morgan A. D. The Pathogenesis of Coronary Occlusion. Oxford: Blackwell Scientific Publications; 1956
• 47 Movat H. Z, MacMorine D. R. L, Takeuchi Y, Burrowes C. E. Chemical mediators released by PMN-leukocytes during phagocytosis of Ag–Ab complexes. In Movat H. Z. (ed.) Cellular and Humoral Mechanisms of Anaphylaxis and Allergy . Karger: New York; 1969: 164
• 48 Murphy E. A, Rowsell H. C, Downie H. G, Robinson G. A, Mustard J. F. Encrustation and atherosclerosis : The analogy between early in vivo lesions and deposits which occur in extracorporeal circulations. Canadian Medical Association Journal 1962; 87: 259
• 49 Mustard J. F, Jørgensen L, Packham M. A. Blood flow and platelet interaction with surfaces. Thrombosis et Diathesis Haemorrhagica Supplement 1972; 51: 151
• 50 Mustard J. F, Kinlough-Rathbone R. L, Packham M. A. Recent status of research in the pathogenesis of thrombosis. Thrombosis et Diathesis Haemorrhagica Supplement 1974; 59: 157
• 51 Mustard J. F, Movat H. Z, MacMorine D. R. L, Senyi A. Release of permeability factors from the blood platelet. Proceedings of the Society for Experimental Biology and Medicine 1965; 119: 988
• 52 Mustard J. F, Murphy E. A. Effect of smoking on blood coagulation and platelet survival in man. British Medical Journal 1963; 1: 846
• 53 Mustard J. P, Perry D. W, Ardlie N. G, Packham M. A. Preparation of suspensions of washed platelets from humans. British Journal of Haematology 1972; 22: 193
• 54 Mustard J. F, Rowsell H. C, Lotz F, Hegardt B, Murphy E. A. The effect of adenine nucleotides on thrombus formation, platelet count and blood coagulation. Experimental and Molecular Pathology 1966; 5: 43
• 55 Nachman R. L, Weksler B, Ferris B. Characterization of human platelet vascular permeability-enhancing activity. Journal of Clinical Investigation 1972; 51: 549
• 56 Nemerson Y, Pitlick F. A. The tissue factor pathway of blood coagulation. In Spaet T. H. (ed.) Progress in Hemostasis and Thrombosis, Volume 1. New York: Grune and Stratton; 1972: 1
• 57 Niewiarowski S, Regoeczi E, Stewart G. J, Senyi A, Mustard J. F. Platelet interaction with polymerizing fibrin. Journal of Clinical Investigation 1972; 51: 685
• 58 Niewiarowski S, Stuart R. K, Thomas D. P. Activation of intravascular coagulation by collagen. Proceedings of the Society for Experimental Biology and Medicine 1966; 123: 196
• 59 Packham M. A, Nishizawa E. E, Mustard J. F. Response of platelets to tissue injury. Biochemical Pharmacology(Supplement). 1968: 171
• 60 Packham M. A, Rowsell H. C, Jørgensen L, Mustard J. F. Localized protein accumulation in the wall of the aorta. Experimental and Molecular Pathology 1967; 7: 214
• 61 Pfueller S. L, Lüscher E. F. The effects of immune complexes on blood platelets and their relationship to complement activation. Immunochemistry 1972; 9: 1151
• 62 Reimers H. J, Packham M. A, Kinlough-Rathbone R. L, Mustard J. F. Effect of repeated treatment of rabbit platelets with low concentrations of thrombin on their function, metabolism and survival. British Journal of Haematology 1973; 25: 675
• 63 Bobbins S. L, Berger R. L, Suda Y, Ryan T. J. Myocardial infarction produced by temporary microcoronary occlusion. Circulation 1969; Supplement (Suppl. 03) 40: 171
• 64 Roberts W. C, Buja L. M. The frequency and significance of coronary arterial thrombi and other observations in fatal acute myocardial infarction – A study of 107 necropsy patients. American Journal of Medicine 1972; 52: 425
• 65 Ross R. The fibroblast and wound repair. Biological Reviews 1968; 43: 51
• 66 Ross R, Glomset J. A. Atherosclerosis and the smooth muscle cell. Science 1973; 180: 1332
• 67 Ross R, Glomset J, Kariya B, Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proceedings of the National Academy of Sciences U.S.A 1974; 71: 1207
• 68 Sinapius D. Häufigkeit und Morphologie der Coronarthrombose und ihre Beziehungen zur antithrombotischen und fibrinolytischen Behandlung. Klinische Wochenschrift 1965; 43: 37
• 69 Somer J. B, Schwartz C. J. Focal [³H] cholesterol uptake in the pig aorta. Part 2. Distribution of [³H] cholesterol across the aortic wall in areas of high and low uptake in vivo. Atherosclerosis 1972; 16: 377
• 70 Stary H. C, McMillan G. C. Kinetics of cellular proliferation in experimental atherosclerosis. Radioautography with grain counts in cholesterol-fed rabbits. Archives of Pathology 1970; 89: 173
• 71 Stemerman M. B, Ross R. Experimental arteriosclerosis. I. Fibrous plaque formation in primates an electron microscope study. Journal of Experimental Medicine 1972; 136: 769
• 72 Thomsen H. K. Carbon monoxideinduced atherosclerosis in primates, an eletronmicroscopic study of the coronary arteries of Macaca irus monkeys. Atherosclerosis 1974; 20: 233
• 73 Torvik A, Jørgensen L. Thrombotic and embolic occlusions of the carotid arteries in an autopsy series. Part 2. Cerebral lesions and clinical course. Journal of Neurological Sciences 1966; 3: 410
• 74 Walsh P. N. The effects of collagen and kaolin on the intrinsic coagulant activity of platelets. Evidence for an alternative pathway in intrinsic coagulation not requiring factor XII. British Journal of Haematology 1972; 22: 393
• 75 Wilner G. D, Nossel H. L, LeRoy E. C. Activation of Hageman factor by collagen. Journal of Clinical Investigation 1968; 47: 2608
• 76 Wright H. P. Endothelial mitosis around aortic branches in normal guineapigs. Nature 1968; 220: 78