Evidence for ozone formation in human atherosclerotic arteries.
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.
Wentworth
Paul
P
Department of Chemistry, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Nieva
Jorge
J
Takeuchi
Cindy
C
Galve
Roger
R
Wentworth
Anita D
AD
Dilley
Ralph B
RB
DeLaria
Giacomo A
GA
Saven
Alan
A
Babior
Bernard M
BM
Janda
Kim D
KD
Eschenmoser
Albert
A
Lerner
Richard A
RA
D001161:Arteriosclerosis / Q000378:metabolism*; D002339:Carotid Arteries / Q000378:metabolism*; D002776:Cholestanes / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D016894:Endarterectomy, Carotid; D005487:Foam Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006835:Hydrazones / Q000378:metabolism; D007203:Indigo Carmine / Q000378:metabolism; D007249:Inflammation; D007962:Leukocytes / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D009654:Norsteroids / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010126:Ozone / Q000378:metabolism*; D026082:Singlet Oxygen / Q000378:metabolism; D013261:Sterols / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C479527:5,6-secosterol; C479528:5-hydroxy-6-formyl-7-norcholesterol; D002776:Cholestanes; D006835:Hydrazones; D008077:Lipoproteins, LDL; D009654:Norsteroids; D013261:Sterols; D026082:Singlet Oxygen; D010126:Ozone; D002784:Cholesterol; D007203:Indigo Carmine; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide