Abstract 15715: Dendritic Cells and Macrophages Contribute Differently to the Initiation of Atherosclerosis
Dendritic cells have been discovered in the atherosclerotic prone areas of blood vessels. Our previous work has shown that the number of dendritic cells increases in the arterial intima of aging and atherosclerotic animal models. Since dendritic cells are professional antigen-presenting cells, we hypothesized that dendritic cells are involved in the initiation of atherosclerosis. To test this hypothesis and compare with the role of macrophages under similar conditions, we crossed conditional dendritic cell depletion mice (DTR-CD11c) or conditional macrophage depletion mice (DTR-CD11b) with ApoE-/- mice. Then we measured aortic plaque formation and dendritic cell and macrophage abundance in the arterial intima at day 10 after a high-fat diet. Our results showed that the atherosclerotic plaques in the aortic roots increased in ApoE-/- mice after 10 days of high-fat diet compared to ApoE-/- mice fed a normal chow diet (high-fat diet: 0.0163 ± 0.0045, n= 6; normal chow diet: 0.0074 ± 0.0023, n= 5; p=0.0031). While high-fat diet augmented the number of dendritic cells in the aorta (high-fat diet: 87 3± 337, n=6; normal chow diet: 356±276, n=3; p=0.0064), few macrophages were observed in ApoE-/- mice with or without high-fat diet. Dendritic cells in mice fed high-fat diet expressed MHC-Class II and co-stimulatory molecule CD86. The administration of diphtheria toxin (DT) yielded a decrease of approximately 50% of aortic dendritic cells in DTR-CD11c/ApoE-/- mice compared to ApoE-/- mice (DTR-CD11c/ApoE-/-: 432 ± 162, n=4; ApoE-/-: 873 ± 337, n=6; p= 0.048). The decrease of dendritic cells in DTR-CD11c/ApoE-/- mice was accompanied with a reduction of plaques in the aortic root (DTR-CD11c/ApoE-/-: 0.0066 ± 0.0018, n=4; ApoE-/-: 0.0163 ± 0.0045, n=6; p= 0.0021). In contrast, neither plaques nor dendritic cell numbers were changed in DTR-CD11b/ApoE-/- mice after 10 days of high-fat diet and DT administration. Thus, our data demonstrate a correlation between a brief high-fat diet and the accumulation of dendritic cells in the arterial wall. The reduction of plaques in dendritic cell depletion suggests a critical role for dendritic cells in the initiation of atherosclerosis. In contrast, macrophages do not seem to be required in the early stage of plaque formation.
- © 2012 by American Heart Association, Inc.