Abstract 12286: AnxA5 Decreases Plaque Inflammation of Advanced Atherosclerotic Lesions in Apoe-/- Mice
Introduction: Annexin A5 (anxA5) has been demonstrated to exert anti-inflammatory, anti-coagulant and anti-apoptotic effects through binding cell surface expressed phosphatidylserine. The actions of anxA5 on the pathogenesis of atherosclerosis are incompletely understood. We investigated effects of exogenous anxA5 on plaque morphology and phenotype of advanced lesions in a murine model of atherosclerosis.
Methods and Results: Advanced atherosclerotic lesions were induced in 12 weeks-old apoE-/- mice using a collar placement around the right carotid artery and a high-fat diet. After 5 weeks mice were injected either with anxA5 (1 mg/kg i.p., 3 times a week, n=8) or with vehicle for another 4 weeks.
No change in lesion size was observed between mice injected with anxA5 (0.175±0.026 mm3) and vehicle (0.175±0.042 mm3) in the carotid artery. However, anxA5 reduced plaque macrophage content both in the intima (59% reduction; 6.7±5.6% vs. 16.2±10.2% for anxA5 vs. controls, p≤0.05) and the media (72.9% reduction; 2.3±2.4% vs. 8.5±4.1% for anxA5 vs. controls, p≤0.01) in advanced atherosclerotic lesions as determined by MAC3 immunohistochemistry. These findings were confirmed in advanced lesions of the aortic arch, where a 66.7% reduction in plaque macrophage content was observed with anxA5 compared to controls (2.6±3.2% vs. 7.8±2.5%, p≤0.01). AnxA5 did not change plaque apoptosis, collagen content, smooth muscle cell content or acellular plaque composition after 4 weeks of treatment as determined by immunohistochemistry in advanced carotid lesions (p=ns). An in vitro flow chamber based assay demonstrated that anxA5 inhibited adhesion of monocytes to TNFα-activated endothelial cells.
Conclusion: Short termtreatment with anxA5 decreases plaque inflammation of advanced lesions in a mouse model of atherosclerosis likely through interfering with recruitment of monocytes to the inflamed lesion site. Suppressing chronic inflammation by targeting exposed phosphatidylserine may become a viable strategy to treat patients suffering from advanced atherosclerosis.
- © 2013 by American Heart Association, Inc.