Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48104, United States of America.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48104, United States of America.
Thromb Res. 2019 Oct;182:116-123. doi: 10.1016/j.thromres.2019.08.018. Epub 2019 Aug 23.
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).
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.
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 R = 0.64, p < 0.0001).
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.
静脉系统中丰富的侧支循环与更严重的疾病有关。然而，关于静脉生成和侧支血管随时间的进展，信息仍然匮乏。此外，对于研究静脉侧支循环最常见的临床前模型——小鼠——的相关性，人们知之甚少。本研究的目的是使用磁共振成像（MRI）非侵入性和定量地描述两种深静脉血栓形成的小鼠模型中的侧支静脉发育和进展。
通过下腔静脉结扎模型（n=5）或电解下腔静脉模型（n=5）在 12-14 周龄雄性 C57BL/6 小鼠中诱导静脉血栓形成。使用针对小静脉成像优化的磁共振成像（MRI）方法，在静脉血栓形成后第 2、6、14 和 21 天，对侧支静脉的发展和血栓体积进行定量。
直径约为 150-200μm 的侧支静脉可以在三维空间中追踪。侧支通路受预先存在的解剖结构的影响；双侧下腔静脉分支的小鼠显示出主要的浅侧支通路（腹壁浅静脉和内腹壁静脉），而没有侧支分支的小鼠则显示出强烈的中间侧支通路（生殖静脉和输尿管旁静脉），并且不太可能发展上升的腰侧支。两种模型中的静脉生成程度与血栓体积呈正相关（综合 R=0.64，p<0.0001）。
C57BL/6 小鼠的静脉侧支通路与人类描述的通路一致。侧支通路受预先存在的解剖结构的影响，侧支化的程度与血栓体积相关。
