title: Endothelial endoplasmic reticulum and nitrative stress in endothelial dysfunction in the atherogenic rabbit model.
abstract: Oxidative stress causes endothelial dysfunction which ultimately leads to atherogenesis, yet anti-oxidant therapy has failed to reduce human clinical outcomes. We hypothesise that endoplasmic reticulum stress and oxidative stress are both present in the endothelial layer of aorta with atherosclerosis. Rabbits were fed for 4 weeks a diet supplemented with 1% methionine +0.5% cholesterol (MC). Control animals received a normal diet. The endothelial function of the abdominal aorta was examined using organ bath techniques. Semi-quantitative immunohistochemistry was used to determine endothelial nitrotyrosine (for nitrative/oxidative stress) and glucose regulated protein 78 (GRP 78) and CHOP to determine endoplasmic reticulum stress. Endothelium dependent relaxation in response to acetylcholine significantly decreased in MC. Stress markers were significantly elevated in endothelia in MC compared to control. The total endothelial area examined for GRP78 increased by 8.4±0.25% in MC vs control (p=0.026) and C/EBP homologous protein (CHOP) increased by 21.9±0.05% in MC vs control (p=0.014). Nitrotyrosine increased by 13.3±0.03% in MC vs control (p=0.012).
  
  
  CONCLUSIONS
  Both endoplasmic reticulum stress and nitrative stress are present during endothelial dysfunction. Treatment directed at both stresses might be beneficial in the prevention of atherosclerosis.
authors.affiliation: Department of Medical Physics and Biophysics, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic. Electronic address: kruzliakpeter@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Kruzliak
authors.affiliation: Department of Medical Physics and Biophysics, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Sabo
authors.affiliation: The Centre for Chronic Disease Prevention and Management (CCDPM), College of Health and Biomedicine, Victoria University, St Albans, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Zulli
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D004730:Endothelium, Vascular / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D011817:Rabbits; D026361:Reactive Nitrogen Species / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D026361:Reactive Nitrogen Species
keywords: C/EBP homologous protein; ER stress; Endothelial dysfunction; Nitrative stress