Hepatic oxidative stress, genotoxicity and vascular dysfunction in lean or obese Zucker rats.
Metabolic syndrome is associated with increased risk of cardiovascular disease, which could be related to oxidative stress. Here, we investigated the associations between hepatic oxidative stress and vascular function in pressurized mesenteric arteries from lean and obese Zucker rats at 14, 24 and 37 weeks of age. Obese Zucker rats had more hepatic fat accumulation than their lean counterparts. Nevertheless, the obese rats had unaltered age-related level of hepatic oxidatively damaged DNA in terms of formamidopyrimidine DNA glycosylase (FPG) or human oxoguanine DNA glycosylase (hOGG1) sensitive sites as measured by the comet assay. There were decreasing levels of oxidatively damaged DNA with age in the liver of lean rats, which occurred concurrently with increased expression of Ogg1. The 37 week old lean rats also had higher expression level of Hmox1 and elevated levels of DNA strand breaks in the liver. Still, both strain of rats had increased protein level of HMOX-1 in the liver at 37 weeks. The external and lumen diameters of mesenteric arteries increased with age in obese Zucker rats with no change in media cross-sectional area, indicating outward re-modelling without hypertrophy of the vascular wall. There was increased maximal response to acetylcholine-mediated endothelium-dependent vasodilatation in both strains of rats. Collectively, the results indicate that obese Zucker rats only displayed a modest mesenteric vascular dysfunction, with no increase in hepatic oxidative stress-generated DNA damage despite substantial hepatic steatosis.
Section of Environmental Health, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.
Mille
M
Løhr
Section of Environmental Health, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.
Janne K
JK
Folkmann
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark.
Majid
M
Sheykhzade
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, Grønnegårdsvej 7, 1870 Frederiksberg C, Denmark.
Lars J
LJ
Jensen
Section of Environmental Health, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.
Ali
A
Kermanizadeh
Section of Environmental Health, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.
Steffen
S
Loft
Section of Environmental Health, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.
Peter
P
Møller
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008074:Lipoproteins / Q000235:genetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008638:Mesenteric Arteries / Q000473:pathology / Q000503:physiopathology*; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D018384:Oxidative Stress; D051381:Rats; D011924:Rats, Zucker; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D066253:Vascular Remodeling; D014666:Vasomotor System / Q000503:physiopathology
C462600:ABCG5 protein, mouse; C462601:ABCG8 protein, mouse; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D007328:Insulin; D008074:Lipoproteins; D008565:Membrane Proteins; D051782:Sterol Regulatory Element Binding Protein 2; D014280:Triglycerides; D002784:Cholesterol; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; D043382:DNA-Formamidopyrimidine Glycosylase