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A chronic complex stress (CCS) mouse model consisting of physical and psychosocial stressors of different types and intensities, presented in a random order, was used to evaluate the effects of CCS, a low-carbohydrate, high-protein (LCHP) diet, and both on the development of atherosclerosis in mice.
Eighty-seven mice were randomly divided into a standard chow diet (n = 44) and LCHP diet (n = 43) groups, and both groups were subdivided into groups without and with CCS treatment. Ultrasound biomicroscopy, histopathological and fluorescence immunohistochemical examinations, ELISA, PCR, and flow cytometry were used.
CCS, especially in mice fed a LCHP diet, resulted in increases in the maximum intima media thickness and hypoechoic plaque formation but decreased blood total cholesterol (TCHO) level. These changes were accompanied by endothelial dysfunction and excessive inflammation based on down-regulation of aortic NOS3 mRNA, up-regulation of aortic syndecan-1 and thrombomodulin mRNA, and an increased percentage of CD45-positive cells in the aorta. Stressed mice had up-regulation of aortic nuclear receptor subfamily 3, group C, member 1 (GR) and NF-κB mRNA expressions, and hyperactivity of adrenal gland function based on increased phenylethanolamine-N-methyltransferase (PNMT) and GR-positive cells and up-regulation of GR and PNMT mRNA expressions in the adrenal gland.
CCS-accelerated atherosclerosis may be controlled by aortic endothelial dysfunction and an excessive inflammatory response independent of the blood TCHO level. These may be modulated in part by hyperactivity of the adrenal gland and co-upregulation of aortic GR and NF-κB gene expressions in mice.