Angiogenesis in a porcine von Willebrand disease model

M. von Depka, H. Allerkamp, C. Pfarrer, M. Ekhlasi-Hundrieser, C. Detering, S. Lehner (Hannover, Germany)

Women issues in thrombosis and hemostasis
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: Women with von Willebrand Disease (VWD) type 3 may develop miscarriage during pregnancy. There is evidence that besides its role in coagulation von Willebrand Factor (VWF) is also involved in angiogenesis and defects of this pathway could play a role in miscarriage. For this reason, VWF as well as proteins with known functions in angiogenesis were analysed by immunohistochemistry of several tissues in a pig model comprising all VWD type 3 genotypes (VWD, heterozygous carriers, wildtype).

Methods: We collected uterus tissue samples including the endometrium of two pigs affected by VWD type 3, two heterozygous carriers, and two wildtype individuals. None of these pigs was pregnant. Hematoxylin-eosin-staining was implemented for morphological evaluation of the tissues, especially with regard to possible differences in structure and pattern of blood vessels. In a second step immunohistochemical analyses comparing the expression of angiogenic factors including VWF were performed in VWD-animals, genetic carriers and wildtype pigs.

Results: The initial hematoxylin-eosin-staining on histological sections of the porcine uteri comprising the different genotypes revealed differences of vessel conformation within the lamina propria. Blood vessels of this tissue were small and less numerous in wildtype and heterozygous pigs. In individuals homozygous for VWD, however, they were partly dilated and thin-walled. The immunohistochemical analysis for VWF showed almost no VWF expression in the pigs affected by VWD. In wildtype and heterozygous pigs, expression was obvious in the endothelium. A narrow band of VWF expression apically on the epithel cells as well as partial expression in glands was seen only in wildtype pigs, but not in heterozygous pigs. For some, but not all further angiogenic factors analysed, expression differences were present among the porcine VWD genotypes.

Conclusion: The results of our study confirm effects of VWF on vessel conformation and structure and also on the expression of specific angiogenic factors. Pigs affected by VWD showed almost no expression of VWF and their blood vessels within the uterine lamina propria presented dilated and thin-walled. Expression differences among the genotypes were obvious for specific angiogenic factors.