Defibrinogenation by Arvin Reduces Air-Drying-lnduced Arteriosclerosis in Rat Carotid Artery

Summary

The effects of lowering plasma fibrinogen levels by Arvin injections have been investigated in a rat model of arteriosclerosis. In this model air-drying-induced endothelial denudation of the left carotid artery results in myointimal lesion development. Arvin (2 × 50 Units/kg) was given at 4 and 2 hours prior to surgery, reducing plasma fibrinogen levels at surgery to about 20%. Fibrinogen levels then normalized within 24 hours. Myointimal lesion development was evaluated morphometrically at 14 days after surgery. Statistical analysis of the morphometric data showed that defibrinogenation had resulted in significantly smaller myointimal lesions. Low plasma fibrinogen levels might thus be considered a negative risk factor for intimal smooth muscle cell proliferation in this model.

Keywords

Endothelial injury - Arterioscleros - Rat carotid artery - Rat carotid artery Defibrinogenation - Arvin - Morphometry

• References

• 1 Duguid JB. Thrombosis as a factor in the pathogenesis of coronary atherosclerosis. J Pathol Bacteriol 1946; 58: 207-212
• 2 Woolf N. Thrombosis and atherosclerosis. Br Med Bull 1978; 34: 137-142
• 3 Schwartz CJ, Valente AJ, Kelley JL, Sprague EA, Edwards EH. Thrombosis and the development of atherosclerosis: Rokitansky revisited. Sem Thromb Haemostas 1988; 14: 189-195
• 4 Astrup T. The biological significance of fibrinolysis. Lancet 1956; 2: 565-568
• 5 Niewiarowski S, Rao AK. Contribution of thrombogenic factors to the pathogenesis of atherosclerosis. Prog Cardiovasc Dis 1983; 26: 197-222
• 6 Ross R. The pathogenesis of atherosclerosis - an update. N Engl J Med 1986; 314: 488-500
• 7 Meade TW. Epidemiology of atheroma and thrombosis. In: Haemostasis and Thrombosis. Bloom AL, Thomas DP. eds Churchill Livingstone; Edinburgh: 1981. pp 575-591
• 8 Meade TW. Clotting factors and ischaemic heart disease: the epidemiological evidence. In: Anticoagulants and Myocardial Infarction, A Re-appraisal. Meade TW. eds Wiley; New York: 1984. pp 91-111
• 9 Meade TW, Brozovic M, Chakrabarti RR, Haines AP, Imeson JD, Mellows S, Miller GJ, North WR S, Stirling Y, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park heart study. Lancet 1986; 2: 533-537
• 10 Stone MC, Thorp JM. Plasma fibrinogen, a major coronary risk factor. J R Coll Gen Pract 1985; 35: 565-569
• 11 Wilhelmsen L, Svärdsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-505
• 12 Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease. The Framingham study. J Am Med Assoc 1987; 258: 1183-1186
• 13 Fishman JA, Ryan GB, Karnovsky MJ. Endothelial regeneration in the rat carotid artery and the significance of endothelial denudation in the pathogenesis of myointimal thickening. Lab Invest 1975; 31: 339-354
• 14 Van Pelt-Verkuil E, Van Pelt W, Jense D. Morphometry of air-drying- induced arteriosclerosis in rat carotid artery Effect of air-flow rate. Arteriosclerosis 1983; 3: 441-451
• 15 Van Pelt-Verkuil E, Knoester J, Van Pelt W, Brink M, Jense D, Emeis JJ. Time course of arterial repair following endothelial denudation in the rat carotid artery. A morphometric study in Wistar and Sprague-Dawley rats Virchows Arch 1986; 408: 559-574
• 16 Emeis JJ, Lindeman J, Nieuwenhuizen W. Immunohistochemical localization of fibrin degradation products in tissues. Am J Pathol 1981; 103: 334-337
• 17 Nieuwenhuizen W, Emeis JJ, Hemmink J. Purification and properties of rat α₂-acute phase macroglobulin. Biochim Biophys Acta 1979; 580: 129-139
• 18 Zijp WL. Handleiding voor statistische toetsen. Tjeenk Willink; Groningen: 1974
• 19 Reidy MA, Silver M. Endothelial regeneration. VII. Lack of intimal proliferation after defined injury to rat aorta. Am J Pathol 1985; 2 8: 173-177
• 20 Reidy MA. A reassessment of endothelial injury and arterial lesion formation. Lab Invest 1985; 53: 513-520
• 21 Tiell ML, Stemerman MB, Spaet TH. The influence of the pituitary on arterial intimal proliferation in the rat. Circ Res 1978; 42: 644-649
• 22 Bettmann MA, Stemerman MB, Ransil BJ. The effect of hypophysectomy on experimental endothelial cell regrowth and intimal thickening in the rat. Circ Res 1981; 48: 907-912
• 23 Friedman RJ, Stemerman MB, Wenz B. et al The effect of thrombocytopenia on experimental arteriosclerotic lesion formation in rabbits. Smooth muscle cell proliferation and re-endothelialization J Clin Invest 1977; 60: 1191-1201
• 24 Handley DA, Van Valen RG, Melden MK, Saunders RN. Suppression of rat carotid lesion development by the calcium channel blocker PN 200-110. Am J pathot 1986; 124: 88-93
• 25 Clowes AW, Karnovsky MB. Suppression by heparin of smooth muscle cell proliferation in injured arteries. Nature 1978; 265: 625-626
• 26 Guyton JR, Rosenberg JD, Clowes AW, Karnovsky MJ. Inhibition of rat arterial smooth muscle cell proliferation by heparin. I. In vivo studies with anticoagulant and non-anticoagulant heparin. Circ Res 1980; 46: 625-634
• 27 Handley DA. Current approaches to inhibition of proliferation in atherosclerosis. Drug Dev Res 1985; 6: 167-176
• 28 Dejana E, Languino LR, Polentarutti N. et al. Interaction between fibrinogen and cultured endothelial cell. Induction of migration and specific binding J Clin Invest 1985; 75: 11-18
• 29 Delvos U, Preissner KT, Mliller-Berghaus G. Binding of fibrinogen to cultured bovine endothelial cells. Thromb Haemostas 1985; 53: 26-31
• 30 Clowes AW, Schwartz SM. Significance of quiescent smooth muscle migration in the injured rat carotid artery. Circ Res 1985; 56: 139-145
• 31 Clowes AW, Clowes MM. Kinetics of cellular proliferation after endothelial injury. IV. Heparin inhibits rat smooth muscle mitogenesis and migration. Circ Res 1986; 58: 839-845
• 32 Sapru RP, Chakravarti RN, Moza AK, Kanta A, Kaur U. Effect of selective depletion of fibrinogen on the evolution of cholesterol- induced atherosclerosis in rabbits. Atherosclerosis 1977; 28: 171-179
• 33 Ishida T, Tanaka K. Effects of fibrin and fibrinogen degradation products on the growth of rabbit aortic smooth muscle cells in culture. Atherosclerosis 1982; 44: 161-174
• 34 Davey MG, Liischer EF. Actions of thrombin and other coagulant and proteolytic enzymes on blood platelets. Nature 1967; 216: 857-858
• 35 Aronson DL. Comparison of the actions of thrombin and the thrombin-like venomous enzymes Ancrod and Batroxobin. Thromb Haemostas 1976; 36: 9-13
• 36 Pitney WR, Bell WR, Bolton G. Blood fibrinolytic activity during Arvin therapy. Br J Haematol 1969; 16: 165-171
• 37 Silberman S, Potter EV, Kwaan HC. Effects of Arvin in mice. Immunofluorescent and histochemical studies Exp Mol Pathol 1971; 14: 67-74
• 38 Silberman S, Bernik MB, Potter EV, Kwaan HC. Effects of Ancrod (Arvin) in mice: studies of plasma fibrinogen and fibrinolytic activity. Br J Haematol 1973; 24: 101-113
• 39 Krishnamurti C, Barr CF, Hassett MA, Young GD, Alving BM. Plasminogen activator inhibitor: a regulator of ancrod-induced fibrin deposition in rabbits. Blood 1987; 69: 798-803