Abstract 16624: Nucleoside Tri(di)phosphohydolase 1 Protects Against Thrombosis in a Mouse Model of Deep Vein Thrombosis
Background: Deep venous thrombosis (DVT) mainly affects the large veins of legs and pelvis. Blood clots often embolize to the lung resulting in significant mortality risk. Nucleoside tri(di)phosphohydolase 1 (NTPDase1, also called CD39) residing on the surface of endothelium and certain leukocyte populations exhibit potent anti-inflammatory and anti-coagulant functions. The role for CD39 in venous thrombosis had not been previously investigated. We tested the hypothesis that CD39 plays a protective role in DVT.
Methods: Male Wild Type (WT) and CD39 gene-deleted (CD39-/-) mice underwent inferior vena cava (IVC) ligation. After 48 hours thrombotic IVC's were dissected, fixed, and H&E stained. Thrombi and vessel wall characteristics were assessed, and thrombus area measured by histomorphometry. Inflammatory cells which had accumulated into thrombotic vessel wall were counted. CD39 expression in IVC was evaluated by immunofluorescent microscopy. In a second group of experiments, the IVC and its associated thrombi were weighed.
Results: At 48 hours post-thrombosis, mice lacking CD39 had significantly larger thrombi than WT mice (26.5x103±1.1x103 um² vs 14.6x103±3.6x103um², p=0.04), with more evidence of inflammatory cell infiltration within the thrombus and at the thrombus/vessel interface. A significant difference between CD39-/-and WT IVCs was noted for total inflammatory cell counts (200±36 vs 88±12, p=0.04), and lymphocyte counts (95±25 vs 9±1, p=0.03) per section. Vessel wall thickness was significantly increased in the CD39-/- mice relative to WT (14.53±0.45um vs 7.4±0.45um, p=0.0001), as well as vessel wall weight (6.87mg±1.54mg vs 3.43mg±0.14mg, p<0.05). Immunostaining demonstrates strong expression of CD39 in the WT vessel wall after DVT.
Conclusion: There is a striking increase in local vein wall CD39 expression post-thrombosis, which may serve a protective anti-inflammatory role, including suppressive effects on thrombus formation and leukocyte accumulation.
- © 2011 by American Heart Association, Inc.