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Antioxidants
Special Issues
Role of Lipoprotein Oxidation in Various Diseases
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Role of Lipoprotein Oxidation in Various Diseases

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

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 19665

Special Issue Editor

Dr. Fumiaki Ito

E-Mail Website
Guest Editor
The Institute of Prophylactic Pharmacology, Shinagawa, Tokyo 140-0001, Japan
Interests: Alzheimer's disease; amyloid-beta (Aβ); high-density lipoprotein; oxidative stress
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lipoproteins are large lipid/apolipoprotein complexes that play a major role in the transport of lipids in the plasma and central nervous system. Reactive oxygen species (ROS) at low concentrations play key physiological roles, but their deleterious effect at high concentrations contributes to the etiology of several disease states. Lipid and apolipoprotein constituents in lipoproteins are vulnerable to attack by ROS and form a variety of oxidized products upon oxidation. Oxidative modification of the constituents is expected to compromise the structure and function of lipoproteins and is related to various diseases that include atherosclerosis/cardiovascular disease, Alzheimer’s disease, and diabetes. This Special Issue will focus on the oxidation of lipoproteins from various viewpoints, especially concerning the pathophysiology of lipoprotein oxidation in various diseases.

We invite investigators to submit both original research and review articles that explore the oxidative modification of lipoproteins in various diseases. Potential topics include, but are not limited to the following:

  • Mechanisms for the oxidation of lipoproteins;
  • Identifications of lipoprotein oxidation products;
  • Metabolism of oxidized lipoproteins;
  • Functional change in oxidized lipoproteins;
  • Lipoprotein oxidation in vascular- and obesity-related chronic inflammation;
  • Lipoprotein oxidation in atherosclerosis/cardiovascular disease, Alzheimer’s disease, and diabetes;
  • Clinical application of oxidized lipoproteins (diagnosis and antioxidant treatment);
  • Beneficial effects of plant products and physical activity on oxidized lipoprotein-related diseases.

We look forward to your contribution.

Prof. emer Fumiaki Ito
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (5 papers)

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14 pages, 2850 KiB  
Article
Nox2 Deficiency Reduces Cartilage Damage and Ectopic Bone Formation in an Experimental Model for Osteoarthritis
by Nik N. L. Kruisbergen, Irene Di Ceglie, Yvonne van Gemert, Birgitte Walgreen, Monique M. A. Helsen, Annet W. Slöetjes, Marije I. Koenders, Fons A. J. van de Loo, Johannes Roth, Thomas Vogl, Peter M. van der Kraan, Arjen B. Blom, Peter L. E. M. van Lent and Martijn H. J. van den Bosch
Antioxidants 2021, 10(11), 1660; https://doi.org/10.3390/antiox10111660 - 22 Oct 2021
Cited by 7 | Viewed by 2414
Abstract
Osteoarthritis (OA) is a destructive disease of the joint with age and obesity being its most important risk factors. Around 50% of OA patients suffer from inflammation of the synovial joint capsule, which is characterized by increased abundance and activation of synovial macrophages [...] Read more.
Osteoarthritis (OA) is a destructive disease of the joint with age and obesity being its most important risk factors. Around 50% of OA patients suffer from inflammation of the synovial joint capsule, which is characterized by increased abundance and activation of synovial macrophages that produce reactive oxygen species (ROS) via NADPH-oxidase 2 (NOX2). Both ROS and high blood levels of low-density lipoprotein (LDL) are implicated in OA pathophysiology, which may interact to form oxidized LDL (oxLDL) and thereby promote disease. Therefore, targeting NOX2 could be a viable treatment strategy for OA. Collagenase-induced OA (CiOA) was used to compare pathology between wild-type (WT) and Nox2 knockout (Nox2−/−) C57Bl/6 mice. Mice were either fed a standard diet or Western diet (WD) to study a possible interaction between NOX2-derived ROS and LDL. Synovial inflammation, cartilage damage and ectopic bone size were assessed on histology. Extracellular ROS production by macrophages was measured in vitro using the Amplex Red assay. Nox2−/− macrophages produced basal levels of ROS but were unable to increase ROS production in response to the alarmin S100A8 or the phorbol ester PMA. Interestingly, Nox2 deficiency reduced cartilage damage, synovial lining thickness and ectopic bone size, whereas these disease parameters were not affected by WD-feeding. These results suggest that NOX2-derived ROS are involved in CiOA development. Full article
(This article belongs to the Special Issue Role of Lipoprotein Oxidation in Various Diseases)
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15 pages, 3864 KiB  
Article
A Novel Immunoassay for Malondialdehyde-Conjugated Low-Density Lipoprotein Measures Dynamic Changes in the Blood of Patients Undergoing Coronary Artery Bypass Graft Surgery
by Samata S. Pandey, Adam Hartley, Mikhail Caga-Anan, Tareq Ammari, Ameer Hamid Ahmed Khan, Bao Anh Vu Nguyen, Chiari Kojima, Jon Anderson, Steven Lynham, Michael Johns, Dorian O. Haskard and Ramzi Y. Khamis
Antioxidants 2021, 10(8), 1298; https://doi.org/10.3390/antiox10081298 - 17 Aug 2021
Cited by 4 | Viewed by 3015
Abstract
Oxidized low-density lipoproteins play an important role in tissue pathology. In this study, we report a sensitive novel enzyme-linked immunosorbent assay for the detection of malondialdehyde-modified low-density lipoprotein (MDA-LDL), a key component of oxidized LDL. The assay is capable of measuring a variable [...] Read more.
Oxidized low-density lipoproteins play an important role in tissue pathology. In this study, we report a sensitive novel enzyme-linked immunosorbent assay for the detection of malondialdehyde-modified low-density lipoprotein (MDA-LDL), a key component of oxidized LDL. The assay is capable of measuring a variable presence of MDA-LDL within human plasma and serum. We demonstrate the robust nature of the assay on samples stored for over 20 months, as well as high inter-operator reproducibility (r = 0.74, p < 0.0001). The assay was capable of detecting dynamic changes in patient blood samples after coronary artery bypass graft surgery, indicating synthesis or release of MDA-LDL with the oxidative stress of surgery, followed by homeostatic clearance. This robust, sensitive and specific assay for circulating MDA-LDL will serve as a valuable translational tool for the improved detection of oxidative forms of LDL in response to a range of physiological or pathological stimuli, with potential clinical applicability. Full article
(This article belongs to the Special Issue Role of Lipoprotein Oxidation in Various Diseases)
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11 pages, 858 KiB  
Article
Oxidised LDL and Anti-Oxidised LDL Antibodies Are Reduced by Lipoprotein Apheresis in a Randomised Controlled Trial on Patients with Refractory Angina and Elevated Lipoprotein(a)
by Tina Z. Khan, Adam Hartley, Dorian Haskard, Mikhail Caga-Anan, Dudley J. Pennell, Peter Collins, Mahmoud Barbir and Ramzi Khamis
Antioxidants 2021, 10(1), 132; https://doi.org/10.3390/antiox10010132 - 18 Jan 2021
Cited by 5 | Viewed by 2735
Abstract
Aims: An abundance of epidemiological evidence demonstrates that elevated lipoprotein(a) (Lp(a)) represents a significant contributing risk factor towards the development of cardiovascular disease. In particular, raised Lp(a) may play a mechanistic role in patients with refractory angina. Studies have also shown a correlation [...] Read more.
Aims: An abundance of epidemiological evidence demonstrates that elevated lipoprotein(a) (Lp(a)) represents a significant contributing risk factor towards the development of cardiovascular disease. In particular, raised Lp(a) may play a mechanistic role in patients with refractory angina. Studies have also shown a correlation between oxidised LDL (oxLDL) levels and atherosclerotic burden as well as rates of cardiovascular events. Antibodies against oxLDL (anti-oxLDL) are involved in the removal of oxLDL. Lipoprotein apheresis (LA), which removes lipoproteins using extra-corporeal processes, is an established means of reducing Lp(a), and thereby reduces cardiovascular events. The aim of this study was to investigate the effect of LA on oxLDL and anti-oxLDL levels amongst those with refractory angina in the context of raised Lp(a). Methods: We performed a sub-study within a randomised controlled crossover trial involving 20 patients with refractory angina and raised Lp(a) > 500 mg/L, comparing the effect of three months of blinded weekly LA or sham, followed by crossover to the opposite study arm. We utilized enzyme-linked immunosorbent assays (ELISA) to quantify oxLDL and IgG/ IgM anti-oxLDL antibody levels at baseline and following three months of active LA or sham sessions. Results: Following three months of LA, there was a 30% reduction in oxLDL from 0.37 ± 0.06 to 0.26 ± 0.04 with a mean drop of −0.11 units (U) (95% CI −0.13, −0.09) compared to no significant change with sham therapy (p < 0.0001 between treatment arms). LA also led to a 22% reduction in levels of IgG and IgM anti-oxLDL, again with no significant change demonstrated during sham (p = 0.0036 and p = 0.012, respectively, between treatment arms). Conclusion: Amongst patients with refractory angina in the context of elevated Lp(a), LA significantly lowers levels of oxLDL and anti-oxLDL antibodies, representing potential mechanisms by which LA yields symptomatic and prognostic benefits in this patient cohort. Full article
(This article belongs to the Special Issue Role of Lipoprotein Oxidation in Various Diseases)
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13 pages, 2067 KiB  
Article
Transfer and Enzyme-Mediated Metabolism of Oxidized Phosphatidylcholine and Lysophosphatidylcholine between Low- and High-Density Lipoproteins
by Naoko Sawada, Takashi Obama, Mirei Mizuno, Kiyoshi Fukuhara, Sanju Iwamoto, Toshihiro Aiuchi, Tomohiko Makiyama and Hiroyuki Itabe
Antioxidants 2020, 9(11), 1045; https://doi.org/10.3390/antiox9111045 - 26 Oct 2020
Cited by 15 | Viewed by 3373
Abstract
Oxidized low-density lipoprotein (oxLDL) and oxidized high-density lipoprotein (oxHDL), known as risk factors for cardiovascular disease, have been observed in plasma and atheromatous plaques. In a previous study, the content of oxidized phosphatidylcholine (oxPC) and lysophosphatidylcholine (lysoPC) species stayed constant in isolated in [...] Read more.
Oxidized low-density lipoprotein (oxLDL) and oxidized high-density lipoprotein (oxHDL), known as risk factors for cardiovascular disease, have been observed in plasma and atheromatous plaques. In a previous study, the content of oxidized phosphatidylcholine (oxPC) and lysophosphatidylcholine (lysoPC) species stayed constant in isolated in vivo oxLDL but increased in copper-induced oxLDL in vitro. In this study, we prepared synthetic deuterium-labeled 1-palmitoyl lysoPC and palmitoyl-glutaroyl PC (PGPC), a short chain-oxPC to elucidate the metabolic fate of oxPC and lysoPC in oxLDL in the presence of HDL. When LDL preloaded with d13-lysoPC was mixed with HDL, d13-lysoPC was recovered in both the LDL and HDL fractions equally. d13-LysoPC decreased by 50% after 4 h of incubation, while d13-PC increased in both fractions. Diacyl-PC production was abolished by an inhibitor of lecithin-cholesterol acyltransferase (LCAT). When d13-PGPC-preloaded LDL was incubated with HDL, d13-PGPC was transferred to HDL in a dose-dependent manner when both LCAT and lipoprotein-associated phospholipase A2 (Lp-PLA2) were inhibited. Lp-PLA2 in both HDL and LDL was responsible for the hydrolysis of d13-PGPC. These results suggest that short chain-oxPC and lysoPC can transfer between lipoproteins quickly and can be enzymatically converted from oxPC to lysoPC and from lysoPC to diacyl-PC in the presence of HDL. Full article
(This article belongs to the Special Issue Role of Lipoprotein Oxidation in Various Diseases)
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10 pages, 1180 KiB  
Perspective
High-Density Lipoprotein (HDL) Triglyceride and Oxidized HDL: New Lipid Biomarkers of Lipoprotein-Related Atherosclerotic Cardiovascular Disease
by Fumiaki Ito and Tomoyuki Ito
Antioxidants 2020, 9(5), 362; https://doi.org/10.3390/antiox9050362 - 26 Apr 2020
Cited by 42 | Viewed by 7120
Abstract
Lipid markers are well-established predictors of vascular disease. The most frequently measured lipid markers are total cholesterol, high-density lipoprotein (HDL)-cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglyceride. HDL reduces atherosclerosis by multiple mechanisms, leading to a reduced risk of cardiovascular disease, and HDL-C, as [...] Read more.
Lipid markers are well-established predictors of vascular disease. The most frequently measured lipid markers are total cholesterol, high-density lipoprotein (HDL)-cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglyceride. HDL reduces atherosclerosis by multiple mechanisms, leading to a reduced risk of cardiovascular disease, and HDL-C, as a metric of HDL quantity, is inversely associated with cardiovascular disease, independent of LDL-C. However, the quality of the HDL appears to be more important than its quantity, because HDL loses its antiatherogenic functions due to changes in its composition and becomes “dysfunctional HDL”. Although there is evidence of the existence of “dysfunctional HDL”, biomarkers for monitoring dysfunctional HDL in clinical practice have not yet been established. In this review, we propose a new lipid panel for the assessment of dysfunctional HDL and lipoprotein-related atherosclerotic cardiovascular disease. The lipid panel includes the measurement of lipid peroxide and triglyceride contents within HDL particles. Full article
(This article belongs to the Special Issue Role of Lipoprotein Oxidation in Various Diseases)
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