Effects of Myeloperoxidase-Induced Oxidation on Antiatherogenic Functions of High-Density Lipoprotein

Kameda, Takahiro; Ohkawa, Ryunosuke; Yano, Kouji; Usami, Yoko; Miyazaki, Akira; Matsuda, Kazuyuki; Kawasaki, Kenji; Sugano, Mitsutoshi; Tozuka, Minoru

doi:10.1155/2015/592594

Cited by 27 publications

(17 citation statements)

References 39 publications

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“…MPO-ANCA binds MPO exposed on the surface of activated neutrophils expressing MPO and moesin. 17,18,[29][30][31]36 AP1 in HDL plays a central role in reverse cholesterol transport to maintain blood vessel function. Moreover, a moesin-like protein, a glycosylphosphatidylinositol anchor, binds to HDL/AP1 and specifically promotes cholesterol efflux.…”

Section: Resultsmentioning

confidence: 99%

<p>Efficacy of a recombinant single-chain fragment variable region, VasSF, as a new drug for vasculitis</p>

Kameoka¹,

Kishi²,

Koura

et al. 2019

DDDT

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Background: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a pauci-immune disease with the inflammation of the small blood vessels. The efficacies of antibody drugs for induction therapies of vasculitis vary among cases. Here, we developed a novel clone of a single chain Fv region (ScFv) with vasculitis-specific therapeutic potential. Materials and methods: The clone, termed VasSF, was selected from our Escherichia coli expression library of recombinant human ScFv based on the therapeutic efficacy in an SCG/ Kj mouse model of MPO-ANCA-associated vasculitis (MAAV), such as improvement of the urinary score and decreased crescent formation in glomeruli, granulomatous in lung, MPO-ANCA biomarkers, the anti-moesin antibody, and some cytokine levels. Results: We identified vasculitis-associated apolipoprotein A-II (VAP2) as a target molecule of the clone and confirmed the independently-established VAP2 antibodies were also therapeutic in SCG/Kj mice. In MAAV, MPO-ANCA and cytokines stimulate neutrophils by facilitating heterodimer formation of VAP2 with apolipoprotein A-I in HDL. Conclusion: VasSF would constitute a novel antibody drug for vasculitis by suppressing the heterodimer formation of the apolipoproteins.

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Section: Resultsmentioning

confidence: 99%

<p>Efficacy of a recombinant single-chain fragment variable region, VasSF, as a new drug for vasculitis</p>

Kameoka¹,

Kishi²,

Koura

et al. 2019

DDDT

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“…Both proteins and lipids associated with HDL contribute to its anti-inflammatory activity. Modifications of HDL, such as glycation or oxidation, impair the anti-inflammatory capacity of HDL and instead generate particles with pro-inflammatory activity [62][63][64][65]. Furthermore, during an inflammatory response, HDL may undergo profound modifications both in mass and composition.…”

Section: Hdl Structure Composition and Functionsmentioning

confidence: 99%

Biological Consequences of Dysfunctional HDL

Pirillo

Catapano

Norata

2019

CMC

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Epidemiological studies have suggested an inverse correlation between high density lipoprotein (HDL) cholesterol levels and the risk of cardiovascular disease. HDLs promote reverse cholesterol transport (RCT) and possess several putative atheroprotective functions, associated to the anti-inflammatory, anti-thrombotic and anti-oxidant properties as well as to the ability to support endothelial physiology. The assumption that increasing HDL-C levels would be beneficial on cardiovascular disease (CVD), however, has been questioned as, in most clinical trials, HDL-C-raising therapies did not result in improved cardiovascular outcomes. These findings, together with the observations from Mendelian randomization studies showing that polymorphisms mainly or solely associated with increased HDL-C levels did not decrease the risk of myocardial infarction, shift the focus from HDL-C levels toward HDL functional properties. Indeed, HDL from atherosclerotic patients not only exhibit impaired atheroprotective functions but also acquire pro-atherogenic properties and are referred to as "dysfunctional" HDL; this occurs even in the presence of normal or elevated HDL-C levels. Pharmacological approaches aimed at restoring HDL functions may therefore impact more significantly on CVD outcome than drugs used so far to increase HDL-C levels. Aims of this review is to discuss the pathological conditions leading to the formation of dysfunctional HDL and their role in atherosclerosis and beyond.

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“…Furthermore, in pro-inflammatory states, Apo-AI becomes a substrate for myeloperoxidase (MPO), a protein released by macrophages, monocytes and neutrophils, which catalyzes the chlorination or nitration of tyrosyl residues of ApoA-I molecules in HDL. MPO promotes oxidative damage of the HDL particle, which leads to a significant reduction of its anti-inflammatory properties, thus rendering HDL dysfunctional [20] .…”

Section: Factors Affecting Hdl Functionalitymentioning

confidence: 99%

Dysfunctional high-density lipoprotein and atherogenesis

Kosmas¹,

Silverio²,

Sourlas³

et al. 2019

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High-density lipoprotein (HDL) plays a major role in reverse cholesterol transport (RCT) but also exhibits, antiinflammatory, endothelial/vasodilatory, anti-thrombotic, antioxidant, anti-aggregating, anticoagulant and cytoprotective functions, which enhance its protective effect against cardiovascular disease. However, the function of HDL is dependent upon genetic, environmental and lifestyle factors. Modification of the protein or lipid components of HDL in certain conditions may convert the HDL particles from anti-inflammatory to pro-inflammatory and pro-atherogenic by limiting their ability to promote RCT and to prevent LDL modification. In our review, we will present the clinical and scientific data pertaining to the factors and conditions that impair HDL functionality and we will discuss the effects of dysfunctional HDL on atherogenesis.

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Effects of Myeloperoxidase-Induced Oxidation on Antiatherogenic Functions of High-Density Lipoprotein

Cited by 27 publications

References 39 publications

<p>Efficacy of a recombinant single-chain fragment variable region, VasSF, as a new drug for vasculitis</p>

<p>Efficacy of a recombinant single-chain fragment variable region, VasSF, as a new drug for vasculitis</p>

Biological Consequences of Dysfunctional HDL

Dysfunctional high-density lipoprotein and atherogenesis

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