Abstract 14983: Orally Administered Eicosapentaenoic Acid Induce Rapid Regression of Atherosclerosis via Modulating the Phenotype of Dendritic Cells in LDL Receptor-deficient Mice
Background and Purpose: Recent clinical trials demonstrated that regression of atherosclerosis is achieved in human and is associated with decreasing cardiovascular events. Dendritic cells (DCs) were reported to play critical roles in atherogenesis, but roles in atherosclerosis regression are still unknown. A metabolite of eicosapentaenoic acid (EPA) has been described to increase anti-inflammatory DCs that suppress effector T cells through inducing indoleamine 2,3-dioxygenase (IDO). We examined whether administration of EPA could change DC phenotypes and regress established atherosclerosis or not.
Methods and Results: Six-week-old LDL receptor-deficient mice were fed high cholesterol and high fat diet for 8 weeks and atherosclerotic lesions were built up at aortic sinus. At 14 weeks of age, the diet was changed to normal chow with or without 5% EPA and continued for 4 weeks. Only changing the diet and lowering plasma cholesterol could not regress atherosclerosis (+0.02×103μm2) over a 4-week period. EPA treatment significantly regressed atherosclerosis (−89.0±6.3×103μm2, P<0.05) and decreased macrophage, CD4+ T cell, DC numbers, and IL-12 mRNA expressions in atherosclerotic lesions compared to controls. Flow cytometric analysis revealed that EPA treatment decreased CD4+ T cells (P<0.05) and increased anti-inflammatory DCs (CD11c+CD80-CD86-; 25.0±2.9% vs. 20.8±3.1%, P<0.05) which inhibit the inflammatory reactions compared to controls through high expression of IDO. In the presence of the IDO inhibitor, regression of atherosclerosis on the administration of EPA could be canceled, confirming that the effect of EPA was partially mediated through IDO.
Conclusions: We established a new rapid atherosclerosis regression mouse model. EPA treatment besides lowering plasma cholesterol can regress atherosclerosis probably due to changing DC phenotype and modulating immune cell functions.
- © 2010 by American Heart Association, Inc.