Hepatic oxidative stress, genotoxicity and vascular dysfunction in lean or obese Zucker rats
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
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Yn: PLoS ONE, Cyfrol 10, Rhif 3, 04.03.2015, t. e0118773.
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
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T1 - Hepatic oxidative stress, genotoxicity and vascular dysfunction in lean or obese Zucker rats
AU - Løhr, Mille
AU - Folkmann, Janne K
AU - Sheykhzade, Majid
AU - Jensen, Lars J
AU - Kermanizadeh, Ali
AU - Loft, Steffen
AU - Møller, Peter
PY - 2015/3/4
Y1 - 2015/3/4
N2 - 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.
AB - 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.
KW - ATP Binding Cassette Transporter, Subfamily G, Member 5
KW - ATP Binding Cassette Transporter, Subfamily G, Member 8
KW - ATP-Binding Cassette Transporters/genetics
KW - Aging/genetics
KW - Animals
KW - Body Weight
KW - Cholesterol/blood
KW - DNA Damage
KW - DNA Glycosylases/genetics
KW - DNA-Formamidopyrimidine Glycosylase/metabolism
KW - Female
KW - Gene Expression Regulation
KW - Heme Oxygenase-1/genetics
KW - Insulin/blood
KW - Lipoproteins/genetics
KW - Liver/enzymology
KW - Membrane Proteins/genetics
KW - Mesenteric Arteries/pathology
KW - Obesity/genetics
KW - Oxidative Stress
KW - Rats
KW - Rats, Zucker
KW - Sterol Regulatory Element Binding Protein 2/genetics
KW - Triglycerides/blood
KW - Vascular Remodeling
KW - Vasomotor System/physiopathology
U2 - 10.1371/journal.pone.0118773
DO - 10.1371/journal.pone.0118773
M3 - Article
C2 - 25738756
VL - 10
SP - e0118773
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 3
ER -