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Antioxidants
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Antioxidant Role of High-Density Lipoprotein
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Antioxidant Role of High-Density Lipoprotein

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: 15 April 2025 | Viewed by 2359

Special Issue Editor

Prof. Dr. Paul Durrington

E-Mail Website
Guest Editor
Cardiovascular Research Group, Faculty of Biology Medicine and Health, University of Manchester, Manchester M13 9PL, UK
Interests: atherosclerosis; diabetes mellitus; dyslipidaemia; insulin resistance; lipids; lipoproteins

Special Issue Information

Dear Colleagues, 

In the last 25 years, evidence has accumulated that LDL, which has undergone oxidation or glucoxidation, is cytotoxic to endothelial cells, and once it has crossed the arterial endothelium, it can be rapidly taken up by monocyte macrophages and smooth muscle cells in the arterial subintima to form foam cells responsible for the initiation and propagation of atherosclerosis. During the same period, our views about HDL have undergone radical revision: evidence that its anti-atherogenic role is because it is critical for reverse cholesterol transport has proved insubstantial. Most excess cholesterol secreted by the liver is removed before cellular uptake by a process in which HDL is not rate-limiting. Attention continues to be directed towards HDL as an early acceptor of excess intracellular cholesterol, but at the same time, it has been widely reported that HDL can protect LDL and cell membranes against oxidative modification, which can contribute to numerous disease processes besides atheroma. HDL is the repository of numerous proteins and lipids that can potentially protect both tissues and lipoproteins, but particularly in inflammation, HDL can undergo compositional change, rendering it proinflammatory and proatherogenic. This series of reviews and articles highlights the mechanisms and components contributing to the antioxidant role of HDL and the disease associations of HDL in which this characteristic is diminished.

Prof. Dr. Paul Durrington
Guest Editor

Manuscript Submission Information

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Keywords

  • lipoprotein oxidation
  • cell membrane oxidation
  • HDL antioxidant activity
  • glycosylation
  • atherosclerosis

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Published Papers (3 papers)

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Research

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15 pages, 1028 KiB  
Article
Healthier Lipid Profiles of Japanese Adults, Especially in Women with Elevated High-Density Lipoprotein Cholesterol (HDL-C), Are Associated with Low HDL-C Peroxide Content
by Loni Berkowitz-Fiebich, Shelby M. Flaherty, Shinobu Kitayama, Mayumi Karasawa, Norito Kawakami, Attilio Rigotti and Christopher L. Coe
Antioxidants 2024, 13(12), 1434; https://doi.org/10.3390/antiox13121434 - 22 Nov 2024
Viewed by 550
Abstract
Japanese adults typically have healthier lipid profiles than American and European adults and a lower prevalence and later onset of atherosclerotic cardiovascular disease (ASCVD). Many Japanese also have uniquely elevated levels of high-density lipoprotein cholesterol (HDL-C). The following analysis examined the relationship between [...] Read more.
Japanese adults typically have healthier lipid profiles than American and European adults and a lower prevalence and later onset of atherosclerotic cardiovascular disease (ASCVD). Many Japanese also have uniquely elevated levels of high-density lipoprotein cholesterol (HDL-C). The following analysis examined the relationship between HDL-C level and HDL-C peroxide content, a bioindicator of unhealthy lipid metabolism in Japanese adults. Blood samples were collected from 463 participants, 31–84 years of age, who lived in Tokyo. A second blood sample was collected 5 years later from 241 of the participants, allowing us to evaluate the temporal stability of the inverse correlation between HDL-C level and HDL-C peroxide content. Glucoregulation and inflammatory activity were assessed because both can be associated with dyslipidemia and HDL-C dysfunction. Obesity and central adiposity were also considered. Overall, women had healthier HDL-C profiles than men. Elevated HDL-C (>90 mg/dL) was common (16.6%) and found more often in women. Higher HDL-C peroxide content was associated with older age and central adiposity and incremented further when HA1c and CRP were higher. When assessed 5 years later, lower HDL-C peroxide content continued to be evident in adults with higher HDL-C. While similar associations have been described for other populations, most Japanese adults typically had healthier levels of HDL-C with lower HDL-C peroxide content than previously reported for American adults. Full article
(This article belongs to the Special Issue Antioxidant Role of High-Density Lipoprotein)
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Review

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29 pages, 3002 KiB  
Review
The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1
by Hieronim Jakubowski
Antioxidants 2024, 13(11), 1292; https://doi.org/10.3390/antiox13111292 - 25 Oct 2024
Viewed by 566
Abstract
The anti-oxidative and anti-inflammatory properties of high-density lipoprotein (HDL) are thought to be mediated by paraoxonase 1 (PON1), a calcium-dependent hydrolytic enzyme carried on a subfraction of HDL that also carries other anti-oxidative and anti-inflammatory proteins. In humans and mice, low PON1 activity [...] Read more.
The anti-oxidative and anti-inflammatory properties of high-density lipoprotein (HDL) are thought to be mediated by paraoxonase 1 (PON1), a calcium-dependent hydrolytic enzyme carried on a subfraction of HDL that also carries other anti-oxidative and anti-inflammatory proteins. In humans and mice, low PON1 activity is associated with elevated oxidized lipids and homocysteine (Hcy)-thiolactone, as well as proteins that are modified by these metabolites, which can cause oxidative stress and inflammation. PON1-dependent metabolic changes can lead to atherothrombotic cardiovascular disease, Alzheimer’s disease, and cancer. The molecular bases underlying these associations are not fully understood. Biochemical, proteomic, and metabolic studies have significantly expanded our understanding of the mechanisms by which low PON1 leads to disease and high PON1 is protective. The studies discussed in this review highlight the changes in gene expression affecting proteostasis as a cause of the pro-oxidative and pro-inflammatory phenotypes associated with attenuated PON1 activity. Accumulating evidence supports the conclusion that PON1 regulates the expression of anti-oxidative and anti-inflammatory proteins, and that the disruption of these processes leads to disease. Full article
(This article belongs to the Special Issue Antioxidant Role of High-Density Lipoprotein)
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14 pages, 940 KiB  
Review
Protective Role of High-Density Lipoprotein in Multiple Sclerosis
by Agnieszka Damiza-Detmer, Małgorzata Pawełczyk and Andrzej Głąbiński
Antioxidants 2024, 13(11), 1276; https://doi.org/10.3390/antiox13111276 - 23 Oct 2024
Viewed by 671
Abstract
Multiple sclerosis (MS) is a chronic, progressive demyelinating disease with a most likely autoimmune background and a neurodegenerative component. Besides the demyelinating process caused by autoreactive antibodies, an increased permeability in the blood–brain barrier (BBB) also plays a key role. Recently, there has [...] Read more.
Multiple sclerosis (MS) is a chronic, progressive demyelinating disease with a most likely autoimmune background and a neurodegenerative component. Besides the demyelinating process caused by autoreactive antibodies, an increased permeability in the blood–brain barrier (BBB) also plays a key role. Recently, there has been growing interest in assessing lipid profile alterations in patients with MS. As a result of myelin destruction, there is an increase in the level of cholesterol released from cells, which in turn causes disruptions in lipid metabolism homeostasis both in the central nervous system (CNS) and peripheral tissues. Currently, there is a growing body of evidence suggesting a protective role of HDL in MS through its effect on the BBB by decreasing its permeability. This follows from the impact of HDL on the endothelium and its anti-inflammatory effect, mostly by interacting with adhesion molecules like vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and E-selectin. HDL, through its action via sphingosine-1-phosphate, exerts an inhibitory effect on leukocyte migration, and its antioxidant properties contribute to the improvement of the BBB function. In this review, we want to summarize these studies and focus on HDL as a mediator of the anti-inflammatory response in MS. Full article
(This article belongs to the Special Issue Antioxidant Role of High-Density Lipoprotein)
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