Effects of chronic mental stress and atherogenic diet on the immune inflammatory environment in mouse aorta

慢性精神应激和致动脉粥样硬化饮食对小鼠主动脉免疫炎症环境的影响

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作者:Maria Cecilia Garibaldi Marcondes, Viktor Zhukov, Henry Bradlow, Manuel Sanchez-Alavez, Alejandro Sanchez-Alavez Gonzalez, Linda K Curtiss, Bruno Conti

Abstract

Inflammation and stress are regarded as two important atherogenic factors. Because stress can affect leukocyte distribution, we hypothesized that stress-mediated leukocyte extravasation can modify the inflammatory environment of the arterial wall possibly contributing to atherogenesis. To test this hypothesis we evaluated the inflammatory environment of the aorta in C57Bl/6 mice subjected to 3 and 12 months of chronic stress and compared it to age matched non-stressed animals. Experiments were carried out in mice fed regular chow or atherogenic diets. Both treatments increased the expression of vascular and leukocyte adhesion molecules and leukocyte accumulation. At 3 months, stress but not an atherogenic diet elevated the number of CD4 cells, CD8 cells, macrophages, dendritic cells and neutrophils. These changes were associated with elevation of transcripts for ICAM-1 and VCAM-1, E-selectin and neuropeptide Y. At 12 months, stress or high cholesterol acted similarly to elevate the number of CD8 and macrophages, and synergistically on the number of all cell types investigated. At this time-point, strong synergism was also observed on the level of E-selectin and NPY in the aorta, but not in the circulation. Despite these effects, histological and morphological alterations of the arterial wall were severe in the atherogenic diet, but not in the stress groups. Thus, although stress and an atherogenic diet may both affect leukocyte accumulation in the aorta, they may contribute differently to atherogenesis.

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