Mouse inferior vena cava stenosis model with all branches interrupted may help deep vein thrombosis research

Deep vein thrombosis (DVT) is a major cause of morbidity and mortality worldwide. Murine models are critical tools for understanding the DVT mechanism and bridging the bench-to-bedside transition. In 2019, Diaz et al. [ [1] Diaz J.A. Saha P. Cooley B. Palmer O.R. Grover S.P. Mackman N. Wakefield T.W. Henke P.K. Smith A. Lal B.K. Choosing a mouse model of venous thrombosis: a consensus assessment of utility and application. J Thromb Haemost. 2019; 17: 699-707 Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar ] published a consensus of leading experts in venous thrombosis research that provided valuable guidelines for model selection. Currently, one of the most used models is the infrarenal vena cava (IVC) stenosis model introduced by Brill et al. [ [2] Brill A. Fuchs T.A. Chauhan A.K. Yang J.J. De Meyer S.F. Köllnberger M. Wakefield T.W. Lämmle B. Massberg S. Wagner D.D. von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models. Blood. 2011; 117: 1400-1407 Crossref PubMed Scopus (331) Google Scholar ] in 2011. This model was adapted from the St. Thomas stenosis model, which involves a combination of reduced blood flow and endothelial damage [ [3] Singh I. Smith A. Vanzieleghem B. Collen D. Burnand K. Saint-Remy J.M. Jacquemin M. Antithrombotic effects of controlled inhibition of factor VIII with a partially inhibitory human monoclonal antibody in a murine vena cava thrombosis model. Blood. 2002; 99: 3235-3240 Crossref PubMed Scopus (73) Google Scholar ]. By avoiding vascular damage, this model mimics human DVT more closely than those triggered by chemical or physical vessel damage [ [4] Geddings J. Aleman M.M. Wolberg A. Brühl M.L. Massberg S. Mackman N. Strengths and weaknesses of a new mouse model of thrombosis induced by inferior vena cava stenosis: communication from the SSC of the ISTH. J Thromb Haemost. 2014; 12: 571-573 Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar ]. However, the thrombus incidence and size vary, which negatively affects the data interpretation and impairs the model’s application to detect small discrepancies between groups [ [1] Diaz J.A. Saha P. Cooley B. Palmer O.R. Grover S.P. Mackman N. Wakefield T.W. Henke P.K. Smith A. Lal B.K. Choosing a mouse model of venous thrombosis: a consensus assessment of utility and application. J Thromb Haemost. 2019; 17: 699-707 Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar ]. Based on the widely accepted rule of reduction, refinement, and replacement, using a larger number of animals to overcome these shortcomings was not recommended. Thus, it is still required to improve the existing models and develop new ones that would better recapitulate human DVT [ [5] Campos J. Brill A. By word of mouse: using animal models in venous thrombosis research. Platelets. 2020; 31: 447-454 Crossref PubMed Scopus (11) Google Scholar ]. In this letter, we communicate our results and introduce new modifications to the “modified stenosis model” that may be applied as a candidate for the model selection algorithm [ [1] Diaz J.A. Saha P. Cooley B. Palmer O.R. Grover S.P. Mackman N. Wakefield T.W. Henke P.K. Smith A. Lal B.K. Choosing a mouse model of venous thrombosis: a consensus assessment of utility and application. J Thromb Haemost. 2019; 17: 699-707 Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar ] in future DVT research.