Background: Tissue factor (TF) is a pro-coagulant receptor that is thought to promote tumor-associated angiogenesis through MAPK signaling. TF is highly expressed in malignancy and the amount of TF expressed by cancer cells directly correlates with the density of tumor vasculature. Thus it has been suggested that angiogenesis is dependent on TF expression. However, we have reported that TF in pericytes is downregulated during angiogenesis in normal wound healing. TF downregulation is confined to the angiogenesis phase of wound healing and only occurs in pericytes that encircle the angiogenic vessels.

Aims: The goal of this study was to characterize the relationship between TF expression and pericyte function during physiologic angiogenesis using the aortic ring model.

Methods: TF knockout (KO) is embryonic lethal. Therefore, we used low TF-expressing mice. These mice bear two alleles for human TF which are driven by the human TF promoter, resulting in expression of ~1% normal TF levels. Abdominal aortas were harvested from mice aged 4 to 8 weeks, cut into 0.1 cm rings, and cultured in collagen matrices for 21 days. The number of neovessels sprouting from each ring was counted on select days.

Results: Surprisingly, there was no difference in the number of sprouts from WT and low TF-expressing rings at any time point (n=24 rings per group). To further characterize angiogenesis we utilized immunofluorescent staining and confocal microscopy to evaluate pericyte morphology and sprout coverage in 7-day-old cultures. Image J was used to analyze the proportion of the vessel area that stained for the pericyte marker NG2. Results showed no difference in the amount of pericyte coverage or pericyte morphology.

Conclusions: These data suggest that normal aortic ring angiogenesis is maintained despite minimal TF expression. This further suggests that unlike pathologic angiogenesis, the amount of physiologic angiogenesis does not correlate with the amount of expressed TF.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/aortic-ring-angiogenesis-proceeds-normally-despite-minimal-tissue-factor-expression/