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High-Density Lipoproteins in Non-cardiovascular Diseases
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High-Density Lipoproteins in Non-cardiovascular Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 29874

Special Issue Editor

Prof. Dr. Ilaria Zanotti

E-Mail Website
Guest Editor
Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy
Interests: lipid metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite being somewhat controversial, the implication of high-density lipoproteins (HDL) in cardiovascular disease is a generally accepted concept. However, recent compelling data has demonstrated that these lipoproteins may be considered a potential biomarker of a wide array of other pathologies. HDL represent heterogenous particles with peculiar lipid and protein compositions, exerting multiple beneficial activities. Among them, the most well documented are the promotion of cell cholesterol efflux, and antioxidative and anti-inflammatory properties. It has been proposed that low levels of HDL and/or the presence of dysfunctional particles may contribute to the development of neurodegenerative disorders, cancer, autoimmune diseases, pathogen-driven pathologies, and acute organ injury. A better understanding of the mechanisms by which HDL is implicated in the development of these diseases and of which components of the particles are involved may provide novel insights into their ethiopathology and open novel strategies for therapeutical approaches targeting HDL.

In this Special Issue, we welcome all contributions dealing with the cross-talk between HDL and non-cardiovascular diseases. Original articles may report either basic studies of biochemistry, molecular biology, and molecular medicine. Moreover, narrative or systemic reviews are well accepted.

Prof. Dr. Ilaria Zanotti
Guest Editor

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Keywords


  • cancer
  • HDL
  • inflammation
  • neurodegenerative disease
  • preclinical studies
  • sepsis
  • therapy

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Published Papers (8 papers)

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Editorial

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6 pages, 239 KiB  
Editorial
High-Density Lipoproteins in Non-Cardiovascular Diseases
by Ilaria Zanotti
Int. J. Mol. Sci. 2022, 23(16), 9413; https://doi.org/10.3390/ijms23169413 - 20 Aug 2022
Viewed by 1311
Abstract
High-density lipoproteins (HDLs) represent physiological carriers of lipids and proteins, the activity of which has been related to cardiovascular health for decades [...] Full article
(This article belongs to the Special Issue High-Density Lipoproteins in Non-cardiovascular Diseases)

Research

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12 pages, 1155 KiB  
Article
Effect of High-Density Lipoprotein from Healthy Subjects and Chronic Kidney Disease Patients on the CD14 Expression on Polymorphonuclear Leukocytes
by Gerald Cohen
Int. J. Mol. Sci. 2021, 22(6), 2830; https://doi.org/10.3390/ijms22062830 - 11 Mar 2021
Cited by 4 | Viewed by 1759
Abstract
In uremic patients, high-density lipoprotein (HDL) loses its anti-inflammatory features and can even become pro-inflammatory due to an altered protein composition. In chronic kidney disease (CKD), impaired functions of polymorphonuclear leukocytes (PMNLs) contribute to inflammation and an increased risk of cardiovascular disease. This [...] Read more.
In uremic patients, high-density lipoprotein (HDL) loses its anti-inflammatory features and can even become pro-inflammatory due to an altered protein composition. In chronic kidney disease (CKD), impaired functions of polymorphonuclear leukocytes (PMNLs) contribute to inflammation and an increased risk of cardiovascular disease. This study investigated the effect of HDL from CKD and hemodialysis (HD) patients on the CD14 expression on PMNLs. HDL was isolated using a one-step density gradient centrifugation. Isolation of PMNLs was carried out by discontinuous Ficoll-Hypaque density gradient centrifugation. CD14 surface expression was quantified by flow cytometry. The activity of the small GTPase Rac1 was determined by means of an activation pull-down assay. HDL increased the CD14 surface expression on PMNLs. This effect was more pronounced for HDL isolated from uremic patients. The acute phase protein serum amyloid A (SAA) caused higher CD14 expression, while SAA as part of an HDL particle did not. Lipid raft disruption with methyl-β-cyclodextrin led to a reduced CD14 expression in the absence and presence of HDL. HDL from healthy subjects but not from HD patients decreased the activity of Rac1. Considering the known anti-inflammatory effects of HDL, the finding that even HDL from healthy subjects increased the CD14 expression was unexpected. The pathophysiological relevance of this result needs further investigation. Full article
(This article belongs to the Special Issue High-Density Lipoproteins in Non-cardiovascular Diseases)
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13 pages, 2057 KiB  
Article
High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective Effects
by Alexy Tran-Dinh, Angélique Levoye, David Couret, Lauriane Galle-Treger, Martine Moreau, Sandrine Delbosc, Camille Hoteit, Philippe Montravers, Pierre Amarenco, Thierry Huby and Olivier Meilhac
Int. J. Mol. Sci. 2021, 22(1), 106; https://doi.org/10.3390/ijms22010106 - 24 Dec 2020
Cited by 18 | Viewed by 2759
Abstract
High-density lipoproteins (HDLs) display endothelial protective effects. We tested the role of SR-BI, an HDL receptor expressed by endothelial cells, in the neuroprotective effects of HDLs using an experimental model of acute ischemic stroke. After transient intraluminal middle cerebral artery occlusion (tMCAO), control [...] Read more.
High-density lipoproteins (HDLs) display endothelial protective effects. We tested the role of SR-BI, an HDL receptor expressed by endothelial cells, in the neuroprotective effects of HDLs using an experimental model of acute ischemic stroke. After transient intraluminal middle cerebral artery occlusion (tMCAO), control and endothelial SR-BI deficient mice were intravenously injected by HDLs or saline. Infarct volume and blood-brain barrier (BBB) breakdown were assessed 24 h post tMCAO. The potential of HDLs and the role of SR-BI to maintain the BBB integrity was assessed by using a human cellular model of BBB (hCMEC/D3 cell line) subjected to oxygen-glucose deprivation (OGD). HDL therapy limited the infarct volume and the BBB leakage in control mice relative to saline injection. Interestingly, these neuroprotective effects were thwarted by the deletion of SR-BI in endothelial cells and preserved in mice deficient for SR-BI in myeloid cells. In vitro studies revealed that HDLs can preserve the integrity of the BBB in OGD conditions, and that this effect was reduced by the SR-BI inhibitor, BLT-1. The protection of BBB integrity plays a pivotal role in HDL therapy of acute ischemic stroke. Our results show that this effect is partially mediated by the HDL receptor, SR-BI expressed by endothelial cells. Full article
(This article belongs to the Special Issue High-Density Lipoproteins in Non-cardiovascular Diseases)
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Review

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22 pages, 1989 KiB  
Review
Good Cholesterol Gone Bad? HDL and COVID-19
by George E. G. Kluck, Jeong-Ah Yoo, Emmanuel H. Sakarya and Bernardo L. Trigatti
Int. J. Mol. Sci. 2021, 22(19), 10182; https://doi.org/10.3390/ijms221910182 - 22 Sep 2021
Cited by 23 | Viewed by 5656
Abstract
The transmissible respiratory disease COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide since its first reported outbreak in December of 2019 in Wuhan, China. Since then, multiple studies have shown an inverse correlation between [...] Read more.
The transmissible respiratory disease COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide since its first reported outbreak in December of 2019 in Wuhan, China. Since then, multiple studies have shown an inverse correlation between the levels of high-density lipoprotein (HDL) particles and the severity of COVID-19, with low HDL levels being associated with an increased risk of severe outcomes. Some studies revealed that HDL binds to SARS-CoV-2 particles via the virus’s spike protein and, under certain conditions, such as low HDL particle concentrations, it facilitates SARS-CoV-2 binding to angiotensin-converting enzyme 2 (ACE2) and infection of host cells. Other studies, however, reported that HDL suppressed SARS-CoV-2 infection. In both cases, the ability of HDL to enhance or suppress virus infection appears to be dependent on the expression of the HDL receptor, namely, the Scavenger Receptor Class B type 1 (SR-B1), in the target cells. SR-B1 and HDL represent crucial mediators of cholesterol metabolism. Herein, we review the complex role of HDL and SR-B1 in SARS-CoV-2-induced disease. We also review recent advances in our understanding of HDL structure, properties, and function during SARS-CoV-2 infection and the resulting COVID-19 disease. Full article
(This article belongs to the Special Issue High-Density Lipoproteins in Non-cardiovascular Diseases)
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15 pages, 909 KiB  
Review
High-Density Lipoproteins in Kidney Disease
by Valentina Kon, Hai-Chun Yang, Loren E. Smith, Kasey C. Vickers and MacRae F. Linton
Int. J. Mol. Sci. 2021, 22(15), 8201; https://doi.org/10.3390/ijms22158201 - 30 Jul 2021
Cited by 10 | Viewed by 3246
Abstract
Decades of epidemiological studies have established the strong inverse relationship between high-density lipoprotein (HDL)-cholesterol concentration and cardiovascular disease. Recent evidence suggests that HDL particle functions, including anti-inflammatory and antioxidant functions, and cholesterol efflux capacity may be more strongly associated with cardiovascular disease protection [...] Read more.
Decades of epidemiological studies have established the strong inverse relationship between high-density lipoprotein (HDL)-cholesterol concentration and cardiovascular disease. Recent evidence suggests that HDL particle functions, including anti-inflammatory and antioxidant functions, and cholesterol efflux capacity may be more strongly associated with cardiovascular disease protection than HDL cholesterol concentration. These HDL functions are also relevant in non-cardiovascular diseases, including acute and chronic kidney disease. This review examines our current understanding of the kidneys’ role in HDL metabolism and homeostasis, and the effect of kidney disease on HDL composition and functionality. Additionally, the roles of HDL particles, proteins, and small RNA cargo on kidney cell function and on the development and progression of both acute and chronic kidney disease are examined. The effect of HDL protein modification by reactive dicarbonyls, including malondialdehyde and isolevuglandin, which form adducts with apolipoprotein A-I and impair proper HDL function in kidney disease, is also explored. Finally, the potential to develop targeted therapies that increase HDL concentration or functionality to improve acute or chronic kidney disease outcomes is discussed. Full article
(This article belongs to the Special Issue High-Density Lipoproteins in Non-cardiovascular Diseases)
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16 pages, 1373 KiB  
Review
HDL Cholesterol and Non-Cardiovascular Disease: A Narrative Review
by Emilie W. Kjeldsen, Liv T. Nordestgaard and Ruth Frikke-Schmidt
Int. J. Mol. Sci. 2021, 22(9), 4547; https://doi.org/10.3390/ijms22094547 - 27 Apr 2021
Cited by 32 | Viewed by 6335
Abstract
High density lipoprotein (HDL) cholesterol has traditionally been considered the “good cholesterol”, and most of the research regarding HDL cholesterol has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within atherosclerotic cardiovascular disease. Randomized trials aiming [...] Read more.
High density lipoprotein (HDL) cholesterol has traditionally been considered the “good cholesterol”, and most of the research regarding HDL cholesterol has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within atherosclerotic cardiovascular disease. Randomized trials aiming at increasing HDL cholesterol have, however, failed and left questions to what role HDL cholesterol plays in human health and disease. Recent observational studies involving non-cardiovascular diseases have shown that high levels of HDL cholesterol are not necessarily associated with beneficial outcomes as observed for age-related macular degeneration, type II diabetes, dementia, infection, and mortality. In this narrative review, we discuss these interesting associations between HDL cholesterol and non-cardiovascular diseases, covering observational studies, human genetics, and plausible mechanisms. Full article
(This article belongs to the Special Issue High-Density Lipoproteins in Non-cardiovascular Diseases)
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24 pages, 1160 KiB  
Review
Revealing the Role of High-Density Lipoprotein in Colorectal Cancer
by Aleksandra Zeljkovic, Jelena Vekic, Marija Mihajlovic, Tamara Gojkovic, Sandra Vladimirov, Dejan Zeljkovic, Vesna Spasojevic-Kalimanovska and Bratislav Trifunovic
Int. J. Mol. Sci. 2021, 22(7), 3352; https://doi.org/10.3390/ijms22073352 - 25 Mar 2021
Cited by 23 | Viewed by 3757
Abstract
Colorectal cancer (CRC) is a highly prevalent malignancy with multifactorial etiology, which includes metabolic alterations as contributors to disease development. Studies have shown that lipid status disorders are involved in colorectal carcinogenesis. In line with this, previous studies have also suggested that the [...] Read more.
Colorectal cancer (CRC) is a highly prevalent malignancy with multifactorial etiology, which includes metabolic alterations as contributors to disease development. Studies have shown that lipid status disorders are involved in colorectal carcinogenesis. In line with this, previous studies have also suggested that the serum high-density lipoprotein cholesterol (HDL-C) level decreases in patients with CRC, but more recently, the focus of investigations has shifted toward the exploration of qualitative properties of HDL in this malignancy. Herein, a comprehensive overview of available evidences regarding the putative role of HDL in CRC will be presented. We will analyze existing findings regarding alterations of HDL-C levels but also HDL particle structure and distribution in CRC. In addition, changes in HDL functionality in this malignancy will be discussed. Moreover, we will focus on the genetic regulation of HDL metabolism, as well as the involvement of HDL in disturbances of cholesterol trafficking in CRC. Finally, possible therapeutic implications related to HDL will be presented. Given the available evidence, future studies are needed to resolve all raised issues concerning the suggested protective role of HDL in CRC, its presumed function as a biomarker, and eventual therapeutic approaches based on HDL. Full article
(This article belongs to the Special Issue High-Density Lipoproteins in Non-cardiovascular Diseases)
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22 pages, 2445 KiB  
Review
Participation of ABCA1 Transporter in Pathogenesis of Chronic Obstructive Pulmonary Disease
by Stanislav Kotlyarov
Int. J. Mol. Sci. 2021, 22(7), 3334; https://doi.org/10.3390/ijms22073334 - 24 Mar 2021
Cited by 16 | Viewed by 3966
Abstract
Chronic obstructive pulmonary disease (COPD) is the important medical and social problem. According to modern concepts, COPD is a chronic inflammatory disease, macrophages play a key role in its pathogenesis. Macrophages are heterogeneous in their functions, which is largely determined by their immunometabolic [...] Read more.
Chronic obstructive pulmonary disease (COPD) is the important medical and social problem. According to modern concepts, COPD is a chronic inflammatory disease, macrophages play a key role in its pathogenesis. Macrophages are heterogeneous in their functions, which is largely determined by their immunometabolic profile, as well as the features of lipid homeostasis, in which the ATP binding cassette transporter A1 (ABCA1) plays an essential role. The objective of this work is the analysis of the ABCA1 protein participation and the function of reverse cholesterol transport in the pathogenesis of COPD. The expression of the ABCA1 gene in lung tissues takes the second place after the liver, which indicates the important role of the carrier in lung function. The participation of the transporter in the development of COPD consists in provision of lipid metabolism, regulation of inflammation, phagocytosis, and apoptosis. Violation of the processes in which ABCA1 is involved may be a part of the pathophysiological mechanisms, leading to the formation of a heterogeneous clinical course of the disease. Full article
(This article belongs to the Special Issue High-Density Lipoproteins in Non-cardiovascular Diseases)
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