Corticosterone accelerates atherosclerosis in the apolipoprotein E-deficient mouse.
Chronic stress is an important risk factor for atherosclerosis, which is a chief process in the development of cardiovascular disease. Increased circulating levels of corticosterone have been documented in several animal models of chronic stress. However, it remains to be established whether corticosterone is sufficient to exacerbate atherosclerosis. To test this hypothesis, apolipoprotein E (ApoE)-deficient mice were fed a high-fat diet for 13 weeks with exposure to either corticosterone or vehicle in the drinking water (CORT and Con). Corticosterone treatment significantly increased atherosclerotic plaque area at the aortic root. Such exacerbation of atherosclerosis was accompanied by significantly lower levels of circulating white blood cells and serum interleukin-1β (IL-1β), and significantly elevated serum concentrations of total cholesterol, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and small dense low-density lipoprotein (sd-LDL) in CORT mice when compared to Con mice. These findings demonstrate that corticosterone is sufficient to exacerbate atherosclerosis in vivo despite its anti-inflammatory properties and that this marked pro-atherogenic phenotype is primarily associated with increased dyslipidaemia.
Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, Japan; Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Tokyo, Japan. Electronic address: mitsu.okutsu@aoni.waseda.jp.
Mitsuharu
M
Okutsu
Department of Health and Human Physiology, University of Iowa, Iowa City, IA, USA; Obesity Research and Education Initiative, University of Iowa, Iowa City, IA, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA.
Vitor A
VA
Lira
Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, Japan.
Kazuhiko
K
Higashida
School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
Jonathan
J
Peake
Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, Japan; Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Tokyo, Japan.
Mitsuru
M
Higuchi
Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, Japan; Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Tokyo, Japan.
Katsuhiko
K
Suzuki
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D003345:Corticosterone / Q000009:adverse effects* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D050171:Dyslipidemias / Q000378:metabolism; D007249:Inflammation; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000139:chemically induced / Q000473:pathology*; D013312:Stress, Physiological
D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D008055:Lipids; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; C577686:interleukin-6, mouse; D003345:Corticosterone
ApoE-deficient mice; Cholesterol; Dyslipidaemia; Hypothalamic–pituitary–adrenal axis; Stress