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Impact of Antioxidant and Anti-inflammatory Functions of HDL in Diseases

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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Aberrant Oxidation of Biomolecules".

Deadline for manuscript submissions: closed (20 December 2022) | Viewed by 17791

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Special Issue Editors

Dr. Carlo Cervellati

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Guest Editor

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy
Interests: oxidative stress; inflammation; HDL dysfuntion; disease biomarkers; Alzheimer’s disease; metabolic disorders; myeloperoxidase; PON-1
Special Issues, Collections and Topics in MDPI journals

Dr. Judit Marsillach

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Guest Editor

Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
Interests: paraoxonases; oxidative stress; inflammation; adductomics; environmental exposures; neurodegenerative diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is consolidated knowledge that oxidative stress (OxS) represents a key player in the pathogenesis of several diseases and pathophysiological conditions. Paraoxonase-1 (PON1) is a high-density-lipoprotein (HDL)-associated enzyme that endows its carrier with multiple biological functions, including the ability to contrast oxidative damage, protect from the toxicity of specific organophosphorus pesticides, and stimulate cholesterol efflux from macrophages. The impact of PON1 on HDL function relies on finely tuned coordination with apolipoproteins, primarily apolipoprotein A1 (Apo A1), and other (putative) accessory proteins, such as myeloperoxidase (MPO), platelet-activating factor acetylhydrolase, or serum amyloid A. OxS and triggered inflammation modify the HDL proteome and lipidome, leading to a dysfunctional HDL that has reduced antioxidant PON1 levels and accumulates pro-oxidative MPO, giving rise to a self-perpetuating detrimental cycle. This aberrant phenomenon appears to be critical in many pathological processes underlying metabolic, vascular, and neurological diseases.

This research topic will discuss experimental and epidemiological evidence, giving meaningful insight into the role of PON1 and other HDL accessory proteins in the onset/progression of diseases.

Dr. Carlo Cervellati
Dr. Judit Marsillach
Guest Editors

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Keywords

paraoxonases
oxidized LDL
high-density lipoproteins
metabolic diseases
apolipoproteins
cardiovascular disease
neurological disease

Published Papers (7 papers)

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Research

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11 pages, 742 KiB

Open AccessArticle

Lipoprotein-Associated Phospholipase A2 Activity as Potential Biomarker of Vascular Dementia

by Giovanni Zuliani, Judit Marsillach, Alessandro Trentini, Valentina Rosta and Carlo Cervellati

Antioxidants 2023, 12(3), 597; https://doi.org/10.3390/antiox12030597 - 28 Feb 2023

Cited by 2 | Viewed by 1432

Abstract

A wealth of evidence suggests that Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays a relevant role in atherogenesis and inflammation, which in turn are associated with the risk of developing dementia. The aim of this study was to evaluate whether serum Lp-PLA2 activity might be an early and/or late biomarker for different forms of dementia. Serum Lp-PLA2 activity was assessed in older patients with mild cognitive impairment (MCI, n = 166; median clinical follow-up = 29 months), Late-Onset Alzheimer’s disease (LOAD, n = 176), vascular dementia (VAD, n = 43), dementia characterized by an overlap between LOAD and VAD (AD-VAD MIXED dementia) (n = 136), other dementia subtypes (n = 45), and cognitively normal controls (n = 151). We found a significant trend towards higher levels of Lp-PLA2 activity in VAD compared with the other groups (ANOVA, p = 0.028). Similarly, Lp-PLA2 activity was greater in MCI converting to VAD compared with those that did not or did convert to the other types of dementia (ANOVA, p = 0.011). After adjusting for potential confounders, high levels of Lp-PLA2 activity were associated with the diagnosis of VAD (O.R. = 2.38, 95% C.I. = 1.06–5.10), but not with other types of dementia. Our data suggest that increased serum Lp-PLA2 activity may represent a potential biomarker for the diagnosis of VAD. Full article

(This article belongs to the Special Issue Impact of Antioxidant and Anti-inflammatory Functions of HDL in Diseases)

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14 pages, 2020 KiB

Open AccessArticle

Obesity Affects Maternal and Neonatal HDL Metabolism and Function

by Julia T. Stadler, Mireille N. M. van Poppel, Christian Wadsack, Michael Holzer, Anja Pammer, David Simmons, David Hill, Gernot Desoye, Gunther Marsche and DALI Core Investigator Group

Antioxidants 2023, 12(1), 199; https://doi.org/10.3390/antiox12010199 - 14 Jan 2023

Cited by 6 | Viewed by 2886

Abstract

Pregravid obesity is one of the major risk factors for pregnancy complications such as gestational diabetes mellitus (GDM) and an increased risk of cardiovascular events in children of affected mothers. However, the biological mechanisms that underpin these adverse outcomes are not well understood. High-density lipoproteins (HDLs) are antiatherogenic by promoting the efflux of cholesterol from macrophages and by suppression of inflammation. Functional impairment of HDLs in obese and GDM-complicated pregnancies may have long-term effects on maternal and offspring health. In the present study, we assessed metrics of HDL function in sera of pregnant women with overweight/obesity of the DALI lifestyle trial (prepregnancy BMI ≥ 29 kg/m²) and women with normal weight (prepregnancy BMI < 25 kg/m²), as well as HDL functionalities in cord blood at delivery. We observed that pregravid obesity was associated with impaired serum antioxidative capacity and lecithin–cholesterol acyltransferase activity in both mothers and offspring, whereas maternal HDL cholesterol efflux capacity was increased. Interestingly, functionalities of maternal and fetal HDL correlated robustly. GDM did not significantly further alter the parameters of HDL function and metabolism in women with obesity, so obesity itself appears to have a major impact on HDL functionality in mothers and their offspring. Full article

(This article belongs to the Special Issue Impact of Antioxidant and Anti-inflammatory Functions of HDL in Diseases)

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31 pages, 8943 KiB

Open AccessArticle

Oxidized High-Density Lipoprotein Induces Endothelial Fibrosis Promoting Hyperpermeability, Hypotension, and Increased Mortality

by Macarena Rojas, Yolanda Prado, Pablo Tapia, Leandro J. Carreño, Claudio Cabello-Verrugio and Felipe Simon

Antioxidants 2022, 11(12), 2469; https://doi.org/10.3390/antiox11122469 - 15 Dec 2022

Cited by 4 | Viewed by 1577

Abstract

During systemic inflammation, reactive oxygen species (ROS) are generated in the bloodstream, producing large amounts of oxidized HDL (oxHDL). OxHDL loses the vascular protective features of native HDL, acquiring detrimental actions. Systemic inflammation promotes endothelial fibrosis, characterized by adhesion protein downregulation and fibrotic-specific gene upregulation, disrupting endothelial monolayer integrity. Severe systemic inflammatory conditions, as found in critically ill patients in the intensive care unit (ICU), exhibit endothelial hyperpermeability, hypotension, and organ hypoperfusion, promoting organ dysfunction and increased mortality. Because endothelial fibrosis disturbs the endothelium, it is proposed that it is the cellular and molecular origin of endothelial hyperpermeability and the subsequent deleterious consequences. However, whether oxHDL is involved in this process is unknown. The aim of this study was to investigate the fibrotic effect of oxHDL on the endothelium, to elucidate the underlying molecular and cellular mechanism, and to determine its effects on vascular permeability, blood pressure, and mortality. The results showed that oxHDL induces endothelial fibrosis through the LOX-1/NOX-2/ROS/NF-κB pathway, TGF-β secretion, and ALK-5/Smad activation. OxHDL-treated rats showed endothelial hyperpermeability, hypotension, and an enhanced risk of death and mortality, which was prevented using an ALK-5 inhibitor and antioxidant diet consumption. Additionally, the ICU patients showed fibrotic endothelial cells, and the resuscitation fluid volume administered correlated with the plasma oxHDL levels associated with an elevated risk of death and mortality. We conclude that oxHDL generates endothelial fibrosis, impacting blood pressure regulation and survival. Full article

(This article belongs to the Special Issue Impact of Antioxidant and Anti-inflammatory Functions of HDL in Diseases)

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14 pages, 2151 KiB

Open AccessArticle

Low HDL Cholesterol Efflux Capacity Indicates a Fatal Course of COVID-19

by Julia T. Stadler, Harald Mangge, Alankrita Rani, Pero Curcic, Markus Herrmann, Florian Prüller and Gunther Marsche

Antioxidants 2022, 11(10), 1858; https://doi.org/10.3390/antiox11101858 - 21 Sep 2022

Cited by 7 | Viewed by 2805

Abstract

Plasma membrane cholesterol is required for proper trafficking and localization of receptors that facilitate severe acute respiratory syndrome coronavirus 2 infection. High-density lipoproteins (HDL) mobilize plasma membrane cholesterol, and HDL-cholesterol levels are associated with the severity of COVID-19 disease and mortality. However, HDL-cholesterol levels poorly reflect the function of this complex family of particles, and a detailed assessment of COVID-19-associated changes in HDL functionality and its prognostic value is lacking. In the present study, we assessed HDL cholesterol efflux capacity, HDL anti-inflammatory and antioxidant properties, and changes in HDL composition and metabolism in COVID-19 (n = 48) and non-COVID pneumonia patients (n = 32). COVID-19 infection markedly reduced the activity of lecithin-cholesteryl-acyltransferase and functional parameters of HDL, such as the cholesterol efflux capacity, arylesterase activity of paraoxonase 1, and anti-oxidative capacity of apoB-depleted serum when compared to non-COVID pneumonia at baseline, paralleled by markedly reduced levels of HDL-cholesterol. Of particular interest, low HDL cholesterol efflux capacity was associated with increased mortality risk in COVID-19 patients, independent of HDL-C levels. Our results highlight profound effects of COVID-19 infection on HDL function, metabolism, and composition. Low HDL cholesterol efflux capacity indicates a fatal course of COVID-19, independent of HDL-cholesterol levels. Full article

(This article belongs to the Special Issue Impact of Antioxidant and Anti-inflammatory Functions of HDL in Diseases)

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18 pages, 6216 KiB

Open AccessArticle

Ozonated Sunflower Oil Exerted Protective Effect for Embryo and Cell Survival via Potent Reduction Power and Antioxidant Activity in HDL with Strong Antimicrobial Activity

by Kyung-Hyun Cho, Dae-Jin Kang, Hyo-Seon Nam, Ju-Hyun Kim, Su-Young Kim, Jung-Ok Lee and Beom-Joon Kim

Antioxidants 2021, 10(11), 1651; https://doi.org/10.3390/antiox10111651 - 21 Oct 2021

Cited by 13 | Viewed by 2396

Abstract

Ozonated sunflower oil (OSO) has potent antimicrobial effects, making it useful for topical applications to treat various skin diseases. On the other hand, regarding mechanistic insight, the antioxidant activity and cytoprotective effects of OSO are relatively less known. The current study compared the antioxidant ability and protective ability of OSO on cells and embryos against oxidative stress, such as H₂O₂ and oxidized low-density lipoproteins (oxLDL), to investigate its potential applications for wound-healing and anti-infection. OSO showed potent radical scavenging activity and ferric ion reduction ability that was up to 35% and 42% stronger than sunflower oil (SO) as a control in a dose-dependent manner. Measurement of the wavelength-maximum fluorescence (WMF) of high-density lipoproteins (HDL) revealed different behavior between OSO and SO treatment (final 1–16%). The OSO treatment caused a 12 nm red shift of Trp movement from 345 nm (at 0%) to 357 nm (at 16%), while SO caused a 12 nm blue shift of Trp movement from 345 nm (at 0%) to 333 nm (at 16%). The fluorescence intensity of HDL₃ was diminished remarkably by the OSO treatment by up to 80% from the initial level, while SO-treated HDL did not. OSO-treated HDL₃ showed slower electromobility with stronger band intensity and bigger HDL particle sizes than those of SO-treated HDL₃. The paraoxonase-1 (PON-1) activity of HDL₃ was enhanced by a co-treatment of OSO that was up to 2.3 times higher than HDL₃ alone in a dose-dependent manner, whereas the co-treatment of SO even inhibited the PON activity. The cell viability of RAW264.7 by the OSO treatment was 3.3 times higher than the SO treatment at a high dose range (from 10% to 50%, final). The OSO also exhibited more cytoprotective effects than SO in brain microglial cells in the presence of H₂O₂ (final 0.03%); treatment with OSO impeded apoptosis and reduced ROS production more than an SO treatment did. In the presence of H₂O₂ alone, 86 ± 5% of the embryos were killed by cell explosion after 24 h, but a co-treatment of OSO (final 4%) resulted in almost no embryo death (98% survivability). Injection of oxLDL (15 ng of protein) into zebrafish embryos caused acute death, while the co-injection of OSO (final 2%) resulted in 2.8 times higher survivability than oxLDL alone. These results suggest new effects of ozonated oil, such as enhanced antioxidant activity, more cytoprotective ability, and higher embryo protection against oxidative stress. These results may be useful in developing new methods for the quality control of ozonated oil and an assessment of its efficacy. Full article

(This article belongs to the Special Issue Impact of Antioxidant and Anti-inflammatory Functions of HDL in Diseases)

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Review

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25 pages, 889 KiB

Open AccessReview

Phytochemicals as Modulators of Paraoxonase-1 in Health and Diseases

by Zahra Najafi Arab, Danial Khayatan, Seyed Mehrad Razavi, Kimia Zare, Elnaz Kheradkhah, Saeideh Momtaz, Gianna Ferretti, Tiziana Bacchetti, Thozhukat Sathyapalan, Seyed Ahmad Emami, Amir Hossein Abdolghaffari and Amirhossein Sahebkar

Antioxidants 2022, 11(7), 1273; https://doi.org/10.3390/antiox11071273 - 27 Jun 2022

Cited by 8 | Viewed by 2777

Abstract

Chronic diseases such as cardiovascular disease (CVD), atherosclerosis, chronic liver disease, and neurodegenerative diseases are major causes of mortality. These diseases have gained much attention due to their complications, and therefore novel approaches with fewer side effects are an important research topic. Free radicals and oxidative stress are involved in the molecular mechanisms of several diseases. Antioxidants can scavenge free radicals and mitigate their adverse effects. One of the most important antioxidant enzymes are paraoxonases (PONs). These enzymes perform a wide range of physiological activities ranging from drug metabolism to detoxification of neuroleptics. Paraoxonase-1 (PON1) is produced in the liver and then transferred to the bloodstream. It has been demonstrated that PON1 could have beneficial effects in numerous diseases such as atherosclerosis, CVD, diabetes mellitus, and neurodegenerative diseases by modulating relevant signalling pathways involved in inflammation and oxidative stress. These pathways include peroxisome proliferator-activated receptor gamma (PPAR-γ) and protein kinase B/nuclear factor kappa-light-chain-enhancer of activated B cells (AKT/NF-κB)-dependent signalling pathways. Increasing PON1 could potentially have protective effects and reduce the incidence of various diseases by modulating these signalling pathways. Several studies have reported that dietary factors are able to modulate PON1 expression and activity. This review aimed at summarizing the state of the art on the effects of dietary phytochemicals on PON1 enzyme activity and the relevant signalling pathways in different diseases. Full article

(This article belongs to the Special Issue Impact of Antioxidant and Anti-inflammatory Functions of HDL in Diseases)

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27 pages, 923 KiB

Open AccessReview

HDL Accessory Proteins in Parkinson’s Disease—Focusing on Clusterin (Apolipoprotein J) in Regard to Its Involvement in Pathology and Diagnostics—A Review

by Izabela Berdowska, Małgorzata Matusiewicz and Małgorzata Krzystek-Korpacka

Antioxidants 2022, 11(3), 524; https://doi.org/10.3390/antiox11030524 - 09 Mar 2022

Cited by 4 | Viewed by 2886

Abstract

Parkinson’s disease (PD)—a neurodegenerative disorder (NDD) characterized by progressive destruction of dopaminergic neurons within the substantia nigra of the brain—is associated with the formation of Lewy bodies containing mainly α-synuclein. HDL-related proteins such as paraoxonase 1 and apolipoproteins A1, E, D, and J are implicated in NDDs, including PD. Apolipoprotein J (ApoJ, clusterin) is a ubiquitous, multifunctional protein; besides its engagement in lipid transport, it modulates a variety of other processes such as immune system functionality and cellular death signaling. Furthermore, being an extracellular chaperone, ApoJ interacts with proteins associated with NDD pathogenesis (amyloid β, tau, and α-synuclein), thus modulating their properties. In this review, the association of clusterin with PD is delineated, with respect to its putative involvement in the pathological mechanism and its application in PD prognosis/diagnosis. Full article

(This article belongs to the Special Issue Impact of Antioxidant and Anti-inflammatory Functions of HDL in Diseases)

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