Evidence for Ozone Formation in Human Atherosclerotic Arteries

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.

Association of HLA-DRB3*0202 and serum IgG antibodies to Chlamydia pneumoniae with essential hypertension in a highly homogeneous population from Majorca (Balearic Islands, Spain)

“…However, these initial findings may help to elucidate in further studies mechanisms for development of EH. Since the interaction in the risk for EH of one allele of the HLA system (a key element of the immune response) and an infectious agent (C. pneumoniae) has been described in our study, the probability that immune and inflammatory mechanisms are important factors in the pathogenesis of EH (as has been well documented in atherosclerosis at the cellular 21 and biochemical level 22 ) is clearly higher than that previously suspected. On the basis of several experimental findings, [23][24][25][26][27][28] it has been hypothesized that chronic C. pneumoniae infection of the vessels may induce a chronic immune response orchestrated by cytokines and mediated by reactive oxygen intermediates.…”

Analysis of oxysterols by electrospray tandem mass spectrometry

“…It is not known if some of these occur naturally, and there is a need for methods to make comprehensive studies of the nature and levels of oxysterols in tissues and body fluids. This is illustrated by the recent identification of novel oxysterols, formed from cholesterol by the action of ozone, in human tissues [27][28][29][30]. Evidence has been presented for their involvement in the mediation of inflammatory processes associated with the development of atherosclerotic lesions [28], and in the initiation of protein misfolding as occurs in several neurological diseases [29].…”

“…This is illustrated by the recent identification of novel oxysterols, formed from cholesterol by the action of ozone, in human tissues [27][28][29][30]. Evidence has been presented for their involvement in the mediation of inflammatory processes associated with the development of atherosclerotic lesions [28], and in the initiation of protein misfolding as occurs in several neurological diseases [29]. Of these products, 3␤-hydroxy-5-oxo-5,6-secocholestan-6-al (5,6-seco-sterol), a ketoaldehyde, and its aldol condensation product both contain a reactive aldehyde group (Scheme 1).…”

Site-specific modification of Alzheimer's peptides by cholesterol oxidation products enhances aggregation energetics and neurotoxicity

“…1 A) (24), covalently modify A␤ and increase its amyloidogenicity (16)(17)(18)(25)(26)(27). Prior data indicated that cholesterol oxidation products 1 and 2, denoted 1(2) hereafter because they interconvert via an aldol/retro-aldol reaction (16,18,24), react with A␤ via Schiff base formation at the N-terminal ␣-amine of Asp-1 (D1) and the side-chain -amines of Lys-16 (K16) and Lys-28 (K28) (18). Compounds 1 and 2 have been detected by us (18,28) and others (29) in ex vivo human and rat brain samples at combined concentrations of up to 400 pg/mg of wet brain (Ϸ1 M concentration).…”