Von Willebrand Factor and Animal Models: Contributions to Gene Therapy, Thrombotic Thrombocytopenic Purpura, and Coronary Artery Thrombosis

KENNETH M. BRINKHOUS, ROBERT L. REDDICK, MARJORIE S. READ, TIMOTHY C. NICHOLS, DWIGHT A. BELLINGER, THOMAS R. GRIGGS

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Use of animal models of von Willebrand factor (vWF) deficiency, both inherited and induced, continues to advance the knowledge of vWF-related diseases. Three examples are reviewed in this article—von Willebrand's disease (vWD), thrombotic thrombocytopenic purpura, and coronary artery thrombosis. The success of gene transfer by liver and bone marrow transplantation in porcine vWD and canine hemophilia A, with a change in phenotype that establishes improved hemostasis, portends imminent testing of gene therapy in these models. With use of recombinant technology, the phenotype of hemophilia B fibroblasts has been transformed to normal, as evidenced by secretion of the normal hemostatically active protein. This result is a prelude to implantation in hemophilic animals. Thrombotic thrombocytopenic purpura is characterized by qualitative and quantitative alterations in vWF. A new animal model induced by the venom factor botrocetin, a cofactor of vWF, closely mimics the human syndrome. A proposed pathophysiologic mechanism for thrombotic thrombocytopenic purpura is outlined. The third contribution is recognition that occlusive coronary thrombosis is a vWF-dependent condition. Without vWF, as in porcine vWD or normal pigs treated with a monoclonal anti-vWF antibody, occlusive thrombi do not develop, even with luminal stenosis. The thrombogenicity of coronary atheromas, including those with fissures of the fibrous cap, is also vWF-dependent.

Original languageEnglish (US)
Pages (from-to)733-742
Number of pages10
JournalMayo Clinic Proceedings
Volume66
Issue number7
DOIs
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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