This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Upston, J. M. Articles by Stocker, R. Search for Related Content PubMed PubMed Citation Articles by Upston, J. M. Articles by Stocker, R.

(American Journal of Pathology. 2002;160:701-710.)
© 2002 American Society for Investigative Pathology

Regular Articles

Disease Stage-Dependent Accumulation of Lipid and Protein Oxidation Products in Human Atherosclerosis

Joanne M. Upston^*, Xianwa Niu^*, Andrew J. Brown, Ryuichi Mashima^*, Hongjie Wang, Revathy Senthilmohan, Anthony J. Kettle, Roger T. Dean and Roland Stocker^*

From the Departments of Biochemistry^*
andCell Biology,
Heart Research Institute,Camperdown, Sydney, Australia; and the Department ofPathology,
Free Radical Research Group,Christchurch School of Medicine, Christchurch, New Zealand

Oxidative modification of low-density lipoprotein is thought to promote arterial lipid accumulation and atherogenesis. Previous studies reported on the presence of certain lipid or protein oxidation products in lesions, although a systematic investigation measuring several oxidation parameters and the accumulation of nonoxidized lipids and antioxidants at various stages of atherosclerosis has not been performed in the same tissue. Using the intimal lipoprotein-containing fraction of human aortic lesions, we demonstrate here that cholesterol accumulated with lesion development and that this increase was already significant at the fatty streak stage. By comparison, cholesterylesters increased significantly only in fibro-fatty and more complex lesions that also contained significantly increased amounts of cholesterylester hydro(pero)xides and 27-hydroxycholesterol. Cholesterylester hydroxides were the major lipid oxidation product detected. Despite accumulation of oxidized lipid, -tocopherol was also present and maintained at a comparable level over the disease process. Of the oxidized protein moieties measured only o,o-dityrosine increased with disease, although chlorotyrosines were present at relatively high levels in all lesions compared to healthy vessels. Our data show that accumulation of nonoxidized lipid precedes that of oxidized lipid in human aortic lesions.

This article has been cited by other articles:

				R. Harkewicz, K. Hartvigsen, F. Almazan, E. A. Dennis, J. L. Witztum, and Y. I. Miller Cholesteryl Ester Hydroperoxides Are Biologically Active Components of Minimally Oxidized Low Density Lipoprotein J. Biol. Chem., April 18, 2008; 283(16): 10241 - 10251. [Abstract] [Full Text] [PDF]

				M. Valiyaveettil, N. Kar, M. Z. Ashraf, T. V. Byzova, M. Febbraio, and E. A. Podrez Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI Blood, February 15, 2008; 111(4): 1962 - 1971. [Abstract] [Full Text] [PDF]

				T. J. Mocatta, A. P. Pilbrow, V. A. Cameron, R. Senthilmohan, C. M. Frampton, A. M. Richards, and C. C. Winterbourn Plasma Concentrations of Myeloperoxidase Predict Mortality After Myocardial Infarction J. Am. Coll. Cardiol., May 22, 2007; 49(20): 1993 - 2000. [Abstract] [Full Text] [PDF]

				M. A. Atkin, A. Gasper, R. Ullegaddi, and H. J. Powers Oxidative Susceptibility of Unfractionated Serum or Plasma: Response to Antioxidants in Vitro and to Antioxidant Supplementation Clin. Chem., November 1, 2005; 51(11): 2138 - 2144. [Abstract] [Full Text] [PDF]

				K. Choy, K. Beck, F. Y. Png, B. J. Wu, S. B. Leichtweis, S. R. Thomas, J. Y. Hou, K. D. Croft, T. A. Mori, and R. Stocker Processes Involved in the Site-Specific Effect of Probucol on Atherosclerosis in Apolipoprotein E Gene Knockout Mice Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1684 - 1690. [Abstract] [Full Text] [PDF]

				B. Fuhrman, N. Volkova, R. Coleman, and M. Aviram Grape Powder Polyphenols Attenuate Atherosclerosis Development in Apolipoprotein E Deficient (E0) Mice and Reduce Macrophage Atherogenicity J. Nutr., April 1, 2005; 135(4): 722 - 728. [Abstract] [Full Text] [PDF]

				A. J. Kettle, T. Chan, I. Osberg, R. Senthilmohan, A. L. P. Chapman, T. J. Mocatta, and J. S. Wagener Myeloperoxidase and Protein Oxidation in the Airways of Young Children with Cystic Fibrosis Am. J. Respir. Crit. Care Med., December 15, 2004; 170(12): 1317 - 1323. [Abstract] [Full Text] [PDF]

				R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]

				A. Kontush, M. J. Chapman, and R. Stocker Vitamin E Is Not Deficient in Human Atherosclerotic Plaques Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): e139 - e140. [Full Text] [PDF]

				S. Sugiyama, K. Kugiyama, M. Aikawa, S. Nakamura, H. Ogawa, and P. Libby Hypochlorous Acid, a Macrophage Product, Induces Endothelial Apoptosis and Tissue Factor Expression: Involvement of Myeloperoxidase-Mediated Oxidant in Plaque Erosion and Thrombogenesis Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1309 - 1314. [Abstract] [Full Text] [PDF]

				E. Waddington, I. B Puddey, and K. D Croft Red wine polyphenolic compounds inhibit atherosclerosis in apolipoprotein E-deficient mice independently of effects on lipid peroxidation Am. J. Clinical Nutrition, January 1, 2004; 79(1): 54 - 61. [Abstract] [Full Text] [PDF]

				R. Stocker and R. A O'Halloran Dealcoholized red wine decreases atherosclerosis in apolipoprotein E gene-deficient mice independently of inhibition of lipid peroxidation in the artery wall Am. J. Clinical Nutrition, January 1, 2004; 79(1): 123 - 130. [Abstract] [Full Text] [PDF]

				G. Pankhurst, X. L. Wang, D. E. Wilcken, G. Baernthaler, U. Panzenbock, M. Raftery, and R. Stocker Characterization of specifically oxidized apolipoproteins in mildly oxidized high density lipoprotein J. Lipid Res., February 1, 2003; 44(2): 349 - 355. [Abstract] [Full Text] [PDF]