Restraint stress up-regulates lectin-like oxidized low-density lipoprotein receptor-1 in aorta of apolipoprotein E-deficient mice.
Psychological stress is a risk factor for cardiovascular disease including atherosclerosis, but the mechanisms are unknown. The vascular lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in vascular pathology and early atherogenesis. We hypothesized that LOX-1 is up-regulated by psychological stress via the formation of oxygen-derived free radicals, and that treatment with EUK-8 (a superoxide dismutase and catalase mimetic) prevents production of oxygen-derived free radicals and leads to reduced expression of LOX-1 in the vascular wall. As a model for psychological stress, we exposed male apolipoprotein E-deficient mice to repeated restraint stress by placement in a conical tube for 2 h per day for 14 consecutive days. Stressed and control mice were treated with EUK-8 (n = 4-5) or vehicle (n = 4-5). Reactive oxygen species and peroxynitrite levels, as detected by oxidative fluorescence microscopy, were increased in the aortic root of mice exposed to stress compared to those of controls by 212 +/- 22% (mean +/- SEM; p < 0.001) and 110 +/- 6% (p < 0.001), respectively. LOX-1, as detected by immunohistochemistry, was increased by 443 +/- 63% in stressed mice compared to control mice (p < 0.001). EUK-8 reduced reactive oxygen species, peroxynitrite, and LOX-1 levels in stressed mice compared to vehicle-treated stressed mice. To conclude, LOX-1 induced by reactive oxygen species and/or peroxynitrite could be one mechanism by which stress promotes cardiovascular disease.
Andersson
Irene J
IJ
Department of Obstetrics and Gynecology, Women and Children's Health Research Institute, Mazankowski Alberta Heart Institute, Cardiovascular Research Centre, University of Alberta, Edmonton, Canada.
Sankaralingam
Sowndramalingam
S
Davidge
Sandra T
ST
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D001835:Body Weight / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003627:Data Interpretation, Statistical; D005029:Ethylenediamines / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D030421:Peroxynitrous Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012149:Restraint, Physical; D051127:Scavenger Receptors, Class E / Q000096:biosynthesis* / Q000235:genetics*; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology
D000975:Antioxidants; D001057:Apolipoproteins E; D005029:Ethylenediamines; C495138:Olr1 protein, mouse; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C090577:N,N'-bis(salicylideneamino)ethane-manganese(II); D003345:Corticosterone