Abstract 2094: Sex Differences In Venous Thrombus Resolution In Mice With Metabolic Syndrome

Abstract

Introduction: Metabolic syndrome (MS) is highly prevalent and have been shown to be associated with mitochondrial impairment and increased cardiovascular and thrombotic risk. It is less understood how MS impacts venous thrombosis and thrombus resolution and the effect of sex as a biological variable on these processes. We hypothesize that mice with MS will have impaired thrombus resolution, particularly males compared to females. Methods: We used a model of diet-independent MS where wildtype FVB mice that have been born to high fat diet fed mothers exhibit multiple organ manifestations of MS. 29 adult mice underwent surgical induction of deep vein thrombosis (DVT) via inferior vena cava ligation (stasis model) resulting in thrombi formation until day 3 and thrombus resolution until day 7. Immunohistochemistry was used to assess vascular tissue remodeling. Results: Comparing control mice to mice born to obese mothers after DVT, there were no significant differences in thrombus weights on day 3 (1.83±.62 vs 1.48±.53 g/kg, p =.186), suggesting a similar initial thrombus burden. However, mice born to obese mothers had significantly impaired thrombus resolution at day 7 (1.85±.53 vs 1.14±.42 g/kg, Student’s t-test p =.007) as compared to control mice born from mothers fed a regular diet. Importantly, thrombus weights were significantly larger in male offspring of obese mothers as compared to females (2.17±.67 vs 1.43±.26 g/kg, Student’s t test p =.013). Additionally, histology analyses showed associations with increased vein wall collagen deposition (Masson’s trichrome) (25±3 vs 13±4% area stained, Student’s t test, p =.0018) and neovascularization (smooth muscle cell actin) within the thrombi of mice with signs of MS as compared to control mice (70+/-10 vs 40+/-8% area stained, Student’s t test, p =.009). Conclusions: Wildtype mice with diet-independent MS demonstrate diminished thrombus resolution, with males having significantly larger thrombi than females. Impaired DVT resolution was associated with decreased tissue remodeling within the thrombi. These data suggest that MS may induce negative tissue remodeling decreasing thrombus involution and increasing vein wall fibrosis, factors that may increase the likelihood of post thrombotic syndrome.