Porcine von Willebrand disease: implications for the pathophysiology of atherosclerosis and thrombosis.

V. Fuster, T. R. Griggs

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations


A role of von Willebrand factor-mediated platelet function in porcine atherogenesis is strongly suggested by these studies. This influence of platelet function is probably most important in experimental systems that involve long-term observation and low or moderately elevated levels of serum cholesterol. On the other hand, effects of platelet function on development of atherosclerosis in animals with extremely high serum cholesterol levels are difficult to demonstrate and may be of relatively less importance. These observations are consistent with the results of numbers of recent studies describing the relationship of vascular injury to intimal smooth muscle cell proliferation. There is considerable evidence that lipid-rich intimal lesions occur in hypercholesterolemic animals with no antecedent denudation of endothelium or platelet adherence. It is difficult to ascribe intimal proliferation to platelet effects in this setting. On the other hand, endothelial cells, smooth muscle cells, and monocytes, which are all known to be involved in the atherosclerotic process, can produce mitogenic and chemotactic proteins, including platelet-derived growth factor. Therefore, metabolic aberrations of various kinds, including those initiated by mechanical injury or hypercholesterolemia, may promote proliferation in the vascular wall and resultant lesion development. Data from studies of pigs with vWD suggest a contribution of platelets to this process, but the effects of this contribution are modulated by numbers of variables, most of which are yet to be identified. The control of these multiple variables will be necessary before a clear understanding of the magnitude of the platelet-mediated effects can be gained. This will require carefully defined conditions of hypercholesterolemia, special attention to the immunologic variables and study of properly selected vascular segments under known conditions of flow. This later element will be especially important in the study of vWF-mediated platelet function, since shear forces are a critical determinant of vWF function. Systems that model flow conditions in various segments of the aorta, carotid, and coronary arteries are presently under development for this purpose. Finally, studies examining the molecular basis of vWF-mediated and other platelet functions will probably guide the most productive use of these models. Platelet membrane glycoprotein (GP) receptor Ib and the complex GP IIb and IIIa have been shown in ex vivo studies to be binding sites for vWF molecules.(ABSTRACT TRUNCATED AT 400 WORDS)

Original languageEnglish
Pages (from-to)159-183
Number of pages25
JournalProgress in hemostasis and thrombosis
StatePublished - 1986


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