Collateral vein dynamics in mouse models of venous thrombosis: Pathways consistent with humans.

ABSTRACT

INTRODUCTION: Prolific collateralization in the venous system has been associated with more severe disease. However, there is a scarcity of information on venogenesis and collateral vessel progression over time. Further, little is understood regarding the relevance of the most common preclinical model-the mouse-for studying venous collateralization. The purpose of this work was to non-invasively and quantitatively characterize collateral vein development and progression in two murine models of deep vein thrombosis using magnetic resonance imaging (MRI). METHODS: Venous thrombosis (VT) was induced in 12-14-week-old male C57BL/6 mice using either the inferior vena cava (IVC) ligation model (n = 5) or the electrolytic IVC model (n = 5). Magnetic Resonance Imaging (MRI) methods optimized for small venous imaging were used on days 2, 6, 14, and 21 following venous thrombosis induction to quantify collateral development and thrombus volume. RESULTS: Collateral veins ~150-200 µm in diameter could be tracked in three dimensions. Collateral pathways were influenced by pre-existing anatomy; mice with bilateral IVC branches showed a predominant superficial collateral pathway (superficial and internal epigastric veins), whereas mice with no lateral branches exhibited a strong intermediate collateral pathway (gonadal and periureteric veins) and were less likely to develop ascending lumbar collaterals. The degree of venogenesis showed a positive correlation with thrombus volume in both models (combined R2 = 0.64, p < 0.0001). CONCLUSIONS: Venous collateral pathways in C57BL/6 mice are consistent with those described in humans. Collateral pathways are influenced by pre-existing anatomy, and the degree of collateralization correlates with thrombus volume.