Circulating and vein wall P-selectin promote venous thrombogenesis during aging in a rodent model

摘要

Introduction: The objective of this study was to identify the direct relationship between aging and selectin activation during acute venous thrombosis in mice of varying ages. We hypothesized that older animals would have increased venous thrombus formation as a result of age associated-increases of pro-inflammatory molecules within the vein wall when compared to younger animals. Materials and Methods: Deep venous thrombosis (DVT) was induced in 4 and 18 month old C57BL/6 mice using the electrolytic inferior vena cava model (EIM) of DVT. Blood and tissue samples were collected at baseline (TC), 6 hours, and 2 days post-thrombosis induction. Results: Older mice had significantly larger thrombi versus younger mice at 6 H (18.4 ± 6.21 vs. 13.0 ± 4.29 × 10-3 grams, p = 0.0033) and 2D (18.4 ± 4.27 vs. 13.0 ± 5.01 × 10-3 grams, p = 0.0005), higher soluble P-selectin levels at 6 H (13 ± 2.5 vs. 8.4 ± 2.7 ng/mg p = 0.0010) and 2D (12.7 ± 5.0 vs. 5.9 ± 1.3 ng/mg p = 0.0020), and higher vein wall P-selectin levels at 6 H (1.94 × 105 ± 3.56 × 104 vs. 4.81 ± 2.29 × 104 pg/mg p = 0.0001) and 2D (1.38 × 105 ± 5.65 × 104 vs. 3.73 ± 1.66 × 104 pg/mg p = 0.0177). Older animals also had significantly higher platelet numbers at 6 H (841 ± 203.8 vs. 564 ± 164.8 K/μL p = 0.0001), and 2D (1002 ± 342.9 vs. 690 ± 186.1 K/μL p = 0.0003), with corresponding increases in mean platelet volume versus younger mice post thrombosis (p ≤ 0.01). Conclusions: Older animals had significantly larger venous thrombi versus younger animals post-thombosis, as a result of high levels of P-selectin both in the circulation and locally at the level of the vein wall. Expression of local and soluble P-selectin increased with age, resulting in a pro-thrombotic environment not represented in younger mice.