Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 302 (5647): 1053-1056

Copyright © 2003 by the American Association for the Advancement of Science

Evidence for Ozone Formation in Human Atherosclerotic Arteries

Paul Wentworth, Jr.,1,7 Jorge Nieva,4 Cindy Takeuchi,2 Roger Galve,1 Anita D. Wentworth,1 Ralph B. Dilley,5 Giacomo A. DeLaria,5 Alan Saven,4 Bernard M. Babior,3 Kim D. Janda,1 Albert Eschenmoser,1,6 Richard A. Lerner1

Abstract: Here, we report evidence for the production of ozone in human disease. Signature products unique to cholesterol ozonolysis are present within atherosclerotic tissue at the time of carotid endarterectomy, suggesting that ozone production occurred during lesion development. Furthermore, advanced atherosclerotic plaques generate ozone when the leukocytes within the diseased arteries are activated in vitro. The steroids produced by cholesterol ozonolysis cause effects that are thought to be critical to the pathogenesis of atherosclerosis, including cytotoxicity, lipid-loading in macrophages, and deformation of the apolipoprotein B-100 secondary structure. We propose the trivial designation "atheronals" for this previously unrecognized class of steroids.

1 Department of Chemistry, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Department of Immunology, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
3 Department of Molecular and Experimental Medicine, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
4 Division of Hematology and Oncology, The Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
5 Division of Cardiothoracic and Vascular Surgery, The Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
6 Laboratorium für organische Chemie, Eidgenössische Technische Hochschule Hönggerberg HCl-H309, Universitaetstrasse 16 CH-8093 Zürich, Switzerland.
7 Department of Biochemistry, Oxford Glycobiology Institute University of Oxford, South Parks Road, Oxford OX1 3QU, UK.

New views on cellular uptake and trafficking of manufactured nanoparticles.
L. Treuel, X. Jiang, and G. U. Nienhaus (2013)
J R Soc Interface 10, 20120939
   Abstract »    Full Text »    PDF »
Childhood Air Pollutant Exposure and Carotid Artery Intima-Media Thickness in Young Adults.
C. V. Breton, X. Wang, W. J. Mack, K. Berhane, M. Lopez, T. S. Islam, M. Feng, F. Lurmann, R. McConnell, H. N. Hodis, et al. (2012)
Circulation 126, 1614-1620
   Abstract »    Full Text »    PDF »
Controlled Exposure of Healthy Young Volunteers to Ozone Causes Cardiovascular Effects.
R. B. Devlin, K. E. Duncan, M. Jardim, M. T. Schmitt, A. G. Rappold, and D. Diaz-Sanchez (2012)
Circulation 126, 104-111
   Abstract »    Full Text »    PDF »
Chemical Pathology of Homocysteine. V. Thioretinamide, Thioretinaco, and Cystathionine Synthase Function in Degenerative Diseases.
K. S. McCully (2011)
Ann. Clin. Lab. Sci. 41, 301-314
   Abstract »    Full Text »    PDF »
Formation of cholesterol ozonolysis products in vitro and in vivo through a myeloperoxidase-dependent pathway.
S. Tomono, N. Miyoshi, H. Shiokawa, T. Iwabuchi, Y. Aratani, T. Higashi, H. Nukaya, and H. Ohshima (2011)
J. Lipid Res. 52, 87-97
   Abstract »    Full Text »    PDF »
Site-specific modification of Alzheimer's peptides by cholesterol oxidation products enhances aggregation energetics and neurotoxicity.
K. Usui, J. D. Hulleman, J. F. Paulsson, S. J. Siegel, E. T. Powers, and J. W. Kelly (2009)
PNAS 106, 18563-18568
   Abstract »    Full Text »    PDF »
Cholesterol, Reactive Oxygen Species, and the Formation of Biologically Active Mediators.
R. C. Murphy and K. M. Johnson (2008)
J. Biol. Chem. 283, 15521-15525
   Full Text »    PDF »
Homocysteine-induced extracellular superoxide dismutase and its epigenetic mechanisms in monocytes.
Y. Jiang, J. Jiang, J. Xiong, J. Cao, N. Li, G. Li, and S. Wang (2008)
J. Exp. Biol. 211, 911-920
   Abstract »    Full Text »    PDF »
Liquid chromatography-mass spectrometry utilizing multi-stage fragmentation for the identification of oxysterols.
K. Karu, M. Hornshaw, G. Woffendin, K. Bodin, M. Hamberg, G. Alvelius, J. Sjovall, J. Turton, Y. Wang, and W. J. Griffiths (2007)
J. Lipid Res. 48, 976-987
   Abstract »    Full Text »    PDF »
Ozonized Low Density Lipoprotein (ozLDL) Inhibits NF-{kappa}B and IRAK-1-Associated Signaling.
C. Cappello, B. Saugel, K. C. Huth, A. Zwergal, M. Krautkramer, C. Furman, M. Rouis, B. Wieser, H. W. Schneider, D. Neumeier, et al. (2007)
Arterioscler Thromb Vasc Biol 27, 226-232
   Abstract »    Full Text »    PDF »
Free radical biology and medicine: it's a gas, man!.
W. A. Pryor, K. N. Houk, C. S. Foote, J. M. Fukuto, L. J. Ignarro, G. L. Squadrito, and K. J. A. Davies (2006)
Am J Physiol Regulatory Integrative Comp Physiol 291, R491-R511
   Abstract »    Full Text »    PDF »
Secretory IgA, Salivary Peroxidase, and Catalase-Mediated Microbicidal Activity during Hydrogen Peroxide Catabolism in Viridans Streptococci: Pathogen Coaggregation.
Y. Uehara, K. Agematsu, K. Kikuchi, S. Matsuzaki, S. Imai, M. Takamoto, K. Sugane, T. Sugiura, Y. Konishi, N. Yoshino, et al. (2006)
The Journal of Infectious Disease 194, 98-107
   Abstract »    Full Text »    PDF »
Ferrous Ions and Reactive Oxygen Species Increase Antigen-binding and Anti-inflammatory Activities of Immunoglobulin G.
J. D. Dimitrov, N. D. Ivanovska, S. Lacroix-Desmazes, V. R. Doltchinkova, S. V. Kaveri, and T. L. Vassilev (2006)
J. Biol. Chem. 281, 439-446
   Abstract »    Full Text »    PDF »
Coxibs and cardiovascular risk.
S. A.H. Zaidi (2005)
Can. Med. Assoc. J. 173, 852-853
   Full Text »    PDF »
Role of Oxidative Modifications in Atherosclerosis.
R. Stocker and J. F. Keaney Jr. (2004)
Physiol Rev 84, 1381-1478
   Abstract »    Full Text »    PDF »
Formation of Biologically Active Oxysterols during Ozonolysis of Cholesterol Present in Lung Surfactant.
M. K. Pulfer and R. C. Murphy (2004)
J. Biol. Chem. 279, 26331-26338
   Abstract »    Full Text »    PDF »
A. J. Kettle, B. M. Clark, and C. C. Winterbourn (2004)
J. Biol. Chem. 279, 18521-18525
   Abstract »    Full Text »    PDF »
Metabolite-initiated protein misfolding may trigger Alzheimer's disease.
Q. Zhang, E. T. Powers, J. Nieva, M. E. Huff, M. A. Dendle, J. Bieschke, C. G. Glabe, A. Eschenmoser, P. Wentworth Jr., R. A. Lerner, et al. (2004)
PNAS 101, 4752-4757
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882