High density lipoprotein is targeted for oxidation by myeloperoxidase in rheumatoid arthritis

Vivekanandan-Giri, Anuradha; Slocum, Jessica L.; Byun, Jaeman; Tang, Chongren; Sands, Robin L.; Gillespie, Brenda W.; Heinecke, Jay W.; Saran, Rajiv; Kaplan, Mariana J.; Pennathur, Subramaniam

doi:10.1136/annrheumdis-2012-202033

Cited by 61 publications

(79 citation statements)

References 45 publications

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“…Since oxidative stress can accompany inflammation (64,65), it is possible that oxidation of apoA-I also accounts in part for the impaired ability of HDL to facilitate efflux. MPO targets apoA-I for site-specific oxidation in human subjects with rheumatoid arthritis (66) and in atherosclerotic lesions (36). Moreover, HDL from atherosclerotic humans have impaired ABCA1-mediated cholesterol efflux and enhanced MPO-mediated apoA-I oxidation (34).…”

Section: Discussionmentioning

confidence: 99%

Serum amyloid A impairs the antiinflammatory properties of HDL

Han¹,

Tang²,

Guevara³

et al. 2015

Journal of Clinical Investigation

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139

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Section: Discussionmentioning

confidence: 99%

Serum amyloid A impairs the antiinflammatory properties of HDL

Han¹,

Tang²,

Guevara³

et al. 2015

Journal of Clinical Investigation

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139

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“…This study used macrophages containing radiolabeled cholesterol to assess the impact of SAA on HDL function. Because the radiolabeled macrophages were injected into the animals' peritoneum only 4 h after endotoxin treatment, while circulating SAA levels in HDL generally peak at approximately 24 h after treatment, it is possible that the ability of HDL to promote effl ux from macrophages, the initial step of reverse cholesterol transport, was not affected by elevated associated with elevated risk of cardiovascular disease (e.g., systemic lupus erythematosus, rheumatoid arthritis) ( 76 ) or acute coronary syndrome ( 77 ). Infl ammatory HDL that is enriched in SAA1 and SAA2 is also depleted in specifi c proteins, including several that may be cardioprotective including apoA-I ( 78 ).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity

Vaisar

Tang

Babenko

et al. 2015

Journal of Lipid Research

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163

132

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Journal of Lipid Research Volume 56, 2015 1519have triggered intense interest in targeting HDL for therapeutic intervention. Several recent observations have cast doubt on the hypotheses that HDL-C levels relate to CAD risk in humans and that elevating HDL-C is therapeutic ( 3, 4 ). For example, genetic variations that alter levels of HDL-C do not always associate with CAD risk, and interventions that elevate HDL-C do not necessarily reduce cardiovascular events in humans with established CAD ( 5 ). Taken together, these observations indicate that HDL is complex and that simply quantifying HDL-C might be a poor way to assess HDL function ( 6, 7 ).The ability of HDL (or serum HDL, serum depleted of apoB-containing lipoproteins) to promote sterol effl ux from cultured macrophages incubated with radiolabeled cholesterol can vary markedly, despite similar levels of HDL-C and apoA-I ( 8 ). Therefore, HDL-C is not necessarily the major determinant of HDL's macrophage sterol effl ux capacity in this system. Importantly, the effl ux capacity of serum HDL is lower in individuals with prevalent CAD ( 9-11 ). A recent study of a large cohort, initially free of CAD, demonstrated that sterol effl ux associates strongly and negatively with the risk of future cardiac events ( 12 ). This association was strengthened by multivariate adjustment, suggesting that impaired HDL function affects incident cardiovascular risk by processes distinct from those involving HDL-C, LDL-cholesterol (LDL-C), and other traditional lipid risk factors. Together, these observations indicate that the sterol effl ux capacity of HDL might be a marker, and perhaps a mediator, of atherosclerotic Abstract Recent studies demonstrate that HDL's ability to promote cholesterol effl ux from macrophages associates strongly with cardioprotection in humans independently of HDL-cholesterol (HDL-C) and apoA-I, HDL's major protein. However, the mechanisms that impair cholesterol effl ux capacity during vascular disease are unclear. Infl ammation, a well-established risk factor for cardiovascular disease, has been shown to impair HDL's cholesterol effl ux capacity. We therefore tested the hypothesis that HDL's impaired effl ux capacity is mediated by specifi c changes of its protein cargo. Humans with acute infl ammation induced by low-level endotoxin had unchanged HDL-C levels, but their HDL-C effl ux capacity was signifi cantly impaired. Proteomic analyses demonstrated that HDL's cholesterol effl ux capacity correlated inversely with HDL content of serum amyloid A (SAA)1 and SAA2. In mice, acute infl ammation caused a marked impairment of HDL-C effl ux capacity that correlated with a large increase in HDL SAA. In striking contrast, the effl ux capacity of mouse infl ammatory HDL was preserved with genetic ablation of SAA1 and SAA2. Our observations indicate that the infl ammatory impairment of HDL-C effl ux capacity is due in part to SAA-mediated remodeling of HDL's protein cargo. -Vaisar, T

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“…atherosclerotic plaque), where MPO also is found. [60][61][62][63] In this case, not only the peroxidase/ H 2 O 2 /NO 2 − system could be implied in nitration, but also ONOO − -dependent nitration promoted by MPO might contribute to the high levels of NO 2 Tyr detected. Undoubtedly, one of the most relevant redox active transition metal complexes in biological systems is hemin (ferriprotoporphyrin IX).…”

mentioning

confidence: 85%

Metal-catalyzed protein tyrosine nitration in biological systems

Campolo¹,

Bartesaghi

Radí

2014

Redox Report

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Protein tyrosine nitration is an oxidative postranslational modification that can affect protein structure and function. It is mediated in vivo by the production of nitric oxide-derived reactive nitrogen species (RNS), including peroxynitrite (ONOO − ) and nitrogen dioxide ( • NO 2 ). Redox-active transition metals such as iron (Fe), copper (Cu), and manganese (Mn) can actively participate in the processes of tyrosine nitration in biological systems, as they catalyze the production of both reactive oxygen species and RNS, enhance nitration yields and provide site-specificity to this process. Early after the discovery that protein tyrosine nitration can occur under biologically relevant conditions, it was shown that some low molecular weight transition-metal centers and metalloproteins could promote peroxynitrite-dependent nitration. Later studies showed that nitration could be achieved by peroxynitrite-independent routes as well, depending on the transition metal-catalyzed oxidation of nitrite (NO 2 − ) to • NO 2 in the presence of hydrogen peroxide. Processes like these can be achieved either by hemeperoxidase-dependent reactions or by ferrous and cuprous ions through Fenton-type chemistry. Besides the in vitro evidence, there are now several in vivo studies that support the close relationship between transition metal levels and protein tyrosine nitration. So, the contribution of transition metals to the levels of tyrosine nitrated proteins observed under basal conditions and, specially, in disease states related with high levels of these metal ions, seems to be quite clear. Altogether, current evidence unambiguously supports a central role of transition metals in determining the extent and selectivity of protein tyrosine nitration mediated both by peroxynitritedependent and independent mechanisms.

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High density lipoprotein is targeted for oxidation by myeloperoxidase in rheumatoid arthritis

Cited by 61 publications

References 45 publications

Serum amyloid A impairs the antiinflammatory properties of HDL

Serum amyloid A impairs the antiinflammatory properties of HDL

Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity

Metal-catalyzed protein tyrosine nitration in biological systems

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