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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.


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