Time-dependent changes to lipids and antioxidants in plasma and aortas of apolipoprotein E knockout mice

Autor: Paul K. Witting, Knut Pettersson, Annika Weston Eriksson, Julie K. Christison, Jacinta Letters, Roland Stocker
Jazyk: angličtina
Rok vydání: 1999
Předmět:
Zdroj: Journal of Lipid Research, Vol 40, Iss 6, Pp 1104-1112 (1999)
ISSN: 0022-2275
Popis: Oxidation of lipoproteins is thought to be an early event in atherogenesis. To evaluate whether aortic li- poprotein lipid (per)oxidation contributes to atherosclero- sis, we investigated the time-dependent changes to lipids and antioxidants in plasma and aortas of apolipoprotein E gene knockout (apoE 2 / 2 ) mice receiving a high fat diet, and compared these changes with lesion development. Cir- culating buoyant lipoproteins and associated cholesterol (C), cholesteryl esters (CE), and a -tocopherol ( a -TOH) in- creased within 1 month then remained largely constant up to 6 months. Coenzyme Q (CoQ) remained unchanged for the first 3 months and increased marginally after 6 months. With increasing duration of the diet, plasma lipids showed an increased propensity to undergo peroxyl radical-induced (per)oxidation. Absolute concentrations of aortic C, hydro- peroxides and hydroxides of CE (CE-O(O)H) and a -TOH increased gradually while aortic CE increased more mark- edly with changes to cholesteryl linoleate being most pro- nounced. Aortic CoQ remained largely unchanged. Overall, the extent of aortic CE (per)oxidation remained low ( < 1%) and the ratio of incremental changes of a -TOH to oxidiz- able lipid remained unchanged. Aortic biochemistry paral- leled lesion formation, particularly that in the descending thoracic aorta. Together, our results show that progress- ing atherosclerosis in apoE 2 / 2 mice is associated with in- creased aortic lipid (per)oxidation as assessed by the con- centrations of CE-O(O)H, measured directly by HPLC. This supports the oxidation theory. Measurement of aortic CE-O(O)H may be useful for mechanistic studies studying the relationship between inhibition of in vivo lipid (per)oxi- dation and atherosclerosis. —Letters, J. M., P. K. Witting, J. K. Christison, A. Weston Eriksson, K. Pettersson, and R. Stocker. Time-dependent changes to lipids and antioxidants in plasma and aortas of apolipoprotein E knockout mice. J. Lipid Res. 1999. 40: 1104-1112.
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