In vivo analysis of thrombus formation in arthritic mice

Abstract

Objectives Rheumatoid arthritis (RA) is characterized by inflammation in multiple joints. In addition to causing joint destruction, the persistent systemic inflammation with RA increases the risk of cardiovascular disease. Although there are in vitro studies showing the prothrombotic effect of inflammatory cytokines, especially TNF, in vivo experimental evidence is lacking due to the complexity of in vivo modeling and observation. In this study, we aimed to model in vivo thrombus formation in arthritic mice and to determine whether the arthritic condition would further promote thrombotic formation. Methods Human TNF-transgenic mice were used as the arthritis model. Thrombus formation was observed on the testicular arterioles. Thrombus formation was induced by reactive oxygen species generated from hematoporphyrin under laser irradiation. Results Platelet thrombus formation was observed in real-time using a laser confocal microscopy in both wild-type and arthritic mice. Quantitative analyses revealed that no significant differences were observed in thrombus formation, represented by platelet attachment time and vascular obstruction time, in our experimental setting. Conclusion Although we confirmed the usefulness of this novel technique for in vivo studies, further investigation is required to conclude the possible mechanism of prothrombotic phenotypes under inflammatory conditions.