title: Brief Communication: Plasma lipid oxidation predicts atherosclerotic status better than cholesterol in diabetic apolipoprotein E deficient mice.
abstract: Increased levels of oxidative stress have been suggested to play a detrimental role in the development of diabetes-related vascular complications. Here, we investigated whether the concentration of malondialdehyde, a marker of lipid oxidation correlated to the degree of aortic plaque lesions in a proatherogenic diabetic mouse model. Three groups of apolipoprotein E knockout mice were studied for 20 weeks, a control, a streptozotocin-induced diabetic, and a diabetic enalapril-treated group. Enalapril was hypothesized to lower oxidative stress level and thus the plaque burden. Both diabetic groups were significantly different from the control group as they had higher blood glucose, HbA1c, total cholesterol, low-density lipoprotein, very low-density lipoprotein, together with a lower high-density lipoprotein concentration and body weight. Animals in the diabetic group had significantly higher plaque area and plasma malondialdehyde than controls. The two diabetic groups did not differ significantly in any measured characteristic. In summary, there was a positive correlation between plasma malondialdehyde concentration and aorta plaque area in apolipoprotein E knockout. Even though further investigation of the role of lipid oxidation in the development of atherosclerosis is warranted, these results suggest that biomarkers of lipid oxidation may be of value in the evaluation of cardiovascular risk.
authors.affiliation: 1 Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Frederiksberg C, Denmark.|2 Department of Incretin and Obesity Pharmacology, Novo Nordisk A/S, DK-2760 Maaloev, Denmark.
authors.forename: Karen Ekkelund
authors.initials: KE
authors.lastname: Petersen
authors.affiliation: 1 Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Frederiksberg C, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.affiliation: 2 Department of Incretin and Obesity Pharmacology, Novo Nordisk A/S, DK-2760 Maaloev, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Raun
authors.affiliation: 3 Department of Diabetes Pharmacology, Novo Nordisk A/S, DK-2760 Maaloev, Denmark.
authors.forename: Günaj
authors.initials: G
authors.lastname: Rakipovski
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D004656:Enalapril / Q000494:pharmacology; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D004656:Enalapril; D002784:Cholesterol
keywords: APOE(-/-) mice; Diabetes; atherosclerosis; lipid oxidation; malondialdehyde; oxidative stress