The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Myeloperoxidase Targets Apolipoprotein A-I, the Major High Density Lipoprotein Protein, for Site-Specific Oxidation in Human Atherosclerotic Lesions
Open accessAbstract
Oxidative damage by myeloperoxidase (MPO) has been proposed to deprive HDL of its cardioprotective effects. In vitro studies reveal that MPO chlorinates and nitrates specific tyrosine residues of apoA-I, the major HDL protein. After Tyr-192 is chlorinated, apoA-I is less able to promote cholesterol efflux by the ABCA1 pathway. To investigate the potential role of this pathway in vivo, we used tandem mass spectrometry with selected reaction monitoring to quantify the regiospecific oxidation of apoA-I. This approach demonstrated that Tyr-192 is the major chlorination site in apoA-I in both plasma and lesion HDL of humans. We also found that Tyr-192 is the major nitration site in apoA-I of circulating HDL but that Tyr-18 is the major site in lesion HDL. Levels of 3-nitrotyrosine strongly correlated with levels of 3-chlorotyrosine in lesion HDL, and Tyr-18 of apoA-I was the major nitration site in HDL exposed to MPO in vitro, suggesting that MPO is the major pathway for chlorination and nitration of HDL in human atherosclerotic tissue. These observations may have implications for treating cardiovascular disease, because recombinant apoA-I is under investigation as a therapeutic agent and mutant forms of apoA-I that resist oxidation might be more cardioprotective than the native form.
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Self-citationIncreased Atherosclerosis in Hyperlipidemic Mice With Inactivation of ABCA1 in Macrophages
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Inflammation and cardiovascular disease: From mechanisms to therapeutics
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High-Density Lipoprotein Function, Dysfunction, and Reverse Cholesterol Transport
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An abundant dysfunctional apolipoprotein A1 in human atheroma
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Metadata
- Authors
- Shao, B., Pennathur, S., & Heinecke, J. W.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 287
- Issue
- 9
- Pages
- 6375-6386
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2031748708
- Cited by
- 170
- References
- 13
- FWCI
- 7.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
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