Evidence for Ozone Formation in Human Atherosclerotic Arteries

Author:

Wentworth Paul12345,Nieva Jorge12345,Takeuchi Cindy12345,Galve Roger12345,Wentworth Anita D.12345,Dilley Ralph B.12345,DeLaria Giacomo A.12345,Saven Alan12345,Babior Bernard M.12345,Janda Kim D.12345,Eschenmoser Albert12345,Lerner Richard A.12345

Affiliation:

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.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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