The von Willebrand Pig as a Model for Atherosclerosis Research^[*]

Summary

In order to evaluate a possible role played by platelets in the development of atherosclerosis, the aortas of 11 control pigs and 11 homozygous von Willebrand (vWd) pigs were examined for spontaneous atherosclerosis. Of the 11 normal pigs, 6 showed multiple atherosclerotic plaques with an intimal thickening of 63 to 130 μm. In contrast, none of the von Willebrand pigs had multiple plaques and only one showed a single lesion of more than 2 mm in diameter.

In a prospective study 5 control pigs and 5 vWd pigs were given a high (2%) cholesterol diet from the age of 3 to 9 months. All of the controls developed atherosclerotic plaques. In 4 of the pigs the plaques exceeded 13% of the aortic surface with an intimal thickening of 50 to 390 pm. In contrast, only one of the vWd pigs developed atherosclerotic plaques which only involved 7% of the aortic surface. Most of the vWd pigs, however, developed non-atherosclerotic flat fatty lesions. These findings may be related to the imp aired platelet arterial wall interaction in vWd. The vWd pigs seem to be an ideal model for atherosclerosis research.

^* Presented at the Vlth International Congress on Thrombosis and Hemostasis, Philadelphia, Pennsylvania, June 21, 1977

• References

• 1 Baumgartner HR, Tschopp TB, Meyer D. 1977; Shear rate dependance of platelet adhesion to collagenous surfaces in Willebrand factor-depleted blood. Borchgrevink CF. 1961; Platelet adhesion in vivo in patients with bleeding disorders. Acta Medica Scandinavica 170: 231
• 3 Bowie EJW, Owen Jr CA. 1973; The value of measuring platelet “adhesiveness” in the diagnosis of bleeding diseases. American Journal of Clinical Pathology 60: 302
• 4 Bowie EJW, Owen Jr CA, Zollman PE, Thompson Jr JH, Fass DN. 1973; Test of hemostasis in swine: Normal values and values in pigs affected with von Willebrand’s disease. American Journal of Vetinary Research 34: 1405
• 5 Fass DN, Brockway WJ, Owen Jr CA, Bowie EJW. 1976; Factor VIII (Willebrand) antigen and ristocetin-Willebrand factor in pigs with von Willebrand’s disease. Thrombosis Research 8: 319
• 6 Fass DN, Didisheim P, Lewis JC, Grabowski EF. 1976. Adhesion of porcine von Willebrand (vWd) platelets (Abstract). Circulation. Suppl 54 II
• 7 Florentin RA, Nam SC. 1969; Dietary-induced atherosclerosis in miniature swine. I. Gross and light microscopy observations: Time of development and morphological characteristics of lesions. Experimental Molecular Pathology 8: 263
• 8 Frost H. 1970. Study of the pathogenesis of obliterating arterial disease by means of tarter electron microscope technique. In Schettler G. (ed.) Platelets and the Vessel Wall-Fibrin Deposition; Symposium of the European Atherosclerosis Group. June 15–17 1969. Georg Thieme Verlag; Stuttgart: 124
• 9 Fry DL. 1969; Certain chemorheologic considerations regarding the blood vascular interface with particular reference to coronary artery disease. Circulation Suppl (Suppl. 39) 40: IV-38-57
• 10 Fry GL, Maca RD, Hoak JC. 1976; Enhancement of endothelial contiguity by human platelets (Abstract). Clinical Research 24: 570
• 11 Fuster V, Bowie EJW, Lewis JC, Fass DN, Owen Jr CA, Brown AL. 1978 Arteriosclerosis in von Willebrand and normal pigs. Spontaneous and high cholesterol diet induced. Journal of Clinical Investigation, in press
• 12 Gimbrone MA, Aster RH, Cotran RS, Corkery J, Jandl JH, Folkman J. 1969; Preservation of vascular integrity in organs perfused in vitro with a platelet-rich medium. Nature (Londen) 222: 33
• 13 Glagov S. 1973; Mechanical stresses on vessels and the non-uniform distribution of atherosclerosis. Medical Clinic of Northern America 57: 63
• 14 Harker LA, Ross R, Slichter SJ, Scott CR. 1976; Homocystine-induced arteriosclerosis: The role of endothelial cell injury and platelet response to its genesis. Journal of Clinical Investigation 58: 731
• 15 Mitchell JRA, Schwartz CJ. 1965. The morphology of arterial plaques. In: Davis FA. (Ed.) Arterial Disease 15-67, Comp; Philadelphia, PA:
• 16 Mustard JF. 1972. Platelets, drugs, and thrombosis, the problem. In: Hirsch J. et al (eds) Platelets, Drugs and Thrombosis: Proceedings of a Symposium McMaster University, Hamilton, Ontario; October 16–18 S. Karger, New York:
• 17 Roskam J. 1964; Du rôle de la paroi vasculaire dans l’hémostase spontanée et la pathogénie des états hémorragiques. Thombosis et Diathesis Haemorrhagica 12: 338
• 18 Ross R, Glomset J, Kariya B, Harker L. 1974; A platelet-dependant serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proceedings of the National Academy of Sciences, U.S.A. 71: 1207
• 19 Ross R, Harker L. 1976; Hyperlipidemia and atherosclerosis: Chronic hyperlipidemia initiates and maintains lesions by endothelial cell disquamation and lipid accumulation. Science 193: 1094
• 20 Silwer J, Cronberg S, Nilsson IM. 1966; Occurrence of arteriosclerosis in von Willebrand’s disease. Acta Medica Scandinavica 180: 475
• 21 Somer JB, Evans G, Schwarta CJ. 1972; Influence of experimental aortic coarctation on the pattern of aortic Evans blue uptake in vivo. Atherosclerosis 16: 127
• 22 Stemmerman MB, Ross R. 1972; Experimental arteriosclerosis. I. Fibrous plaque formation in primates, an electron microscope study. Journal of Experimental Medicine 136: 769
• 23 Sunaga T, Yamashita Y, Numan F, Shimamoto T. 1970 Luminal surface of normal and atherosclerotic arteries observed by scanning electron microscope. SEM/1970 243-248
• 24 Texon M. 1960; The hemodynamic concept of atherosclerosis. Bulletin of the New York Academy of Medicine 36: 263
• 25 Weiss HJ, Hoyer LW, Rickles FR, Varma A, Rogers J. 1973; Quantitative assay of plasma factor deficient in von Willebrand’s disease that is necessary for platelet aggregation: Relationship to Factor VIII procoagulant activity and antigen content. Journal of Clinical Investigation 52: 2708
• 26 Weiss HJ, Tschopp TB, Baumgartner HR. 1975; Impaired interaction (adhesion-aggregation) of platelets with the subendothelium in storagepool disease and after aspirin ingestion: A comparison with von Willebrand’s disease. New England Journal of Medicine 293: 619
• 27 Wesolowski SA, Fries CC, Sabini AM, Sawyer PN. 1965; The significance of turbulence in hemic systems and in the distribution of the atherosclerotic lesion. Surgery 57: 155
• 28 Wojcik JD, Van Horn DL, Webber AJ, Johnson SA. 1969; Mechanism whereby platelets support the endothelium. Transfusion 9: 324
• 29 Zimmerman TS, Ratnoff OD, Powell AE. 1971; Immunologic differentiation of classic hemophilia (Factor VIII deficiency) and von Willebrand’s disease: With observations on combined deficiencies of antihemophilic factor and proaccelerin (Factor V) and on acquired circulating anticoagulant against antihemophilic factor. Journal of Clinical Investigation 50: 244