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High-Density Lipoproteins in Health and Disease

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (20 April 2024) | Viewed by 10698

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Prof. Dr. Ilaria Zanotti

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Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy
Interests: lipid metabolism
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Dear Colleagues,

High density lipoproteins (HDL) are endogenous, heterogeneous particles with peculiar lipid and protein composition, carrying multiple physiological functions that range from the removal of excess cholesterol from cells, to anti-oxidant, anti-inflammatory and antiaggregant properties. Their function is strictly related to the composition, in particular the lipid and protein factions. The implication of HDL in cardiovascular disease has been documented for decades, but some controversial still challenges the identification of these lipoproteins as a well recognized pharmacological target. In addition, recent compelling data demonstrated that HDL may be considered a potential biomarker of a wide array of other pathologies, such as neurodegenerative disorders, cancer, autoimmune diseases, pathogen-driven pathologies, acute organ injury. It has been proposed that low levels of HDL and/or the presence of dysfunctional particles may contribute to the development of all the above mentioned diseases. A better understanding of the mechanisms by which HDL exert their activities and of which components of the particles are involved may open novel strategies for therapeutical approaches targeting HDL.

In this Special Issue, we welcome all contributions dealing with the physio-pathological role of HDL, either characterizing the composition or the function of these lipoproteins. 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

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.

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Keywords

omics
protein
lipid
cardiovascular
neurodegenerative disease
inflammation
preclinical studies
therapy

Published Papers (6 papers)

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Research

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12 pages, 1083 KiB

Open AccessArticle

Reduced High-Density Lipoprotein Cholesterol Is an Independent Determinant of Altered Bone Quality in Women with Type 2 Diabetes

by Sara Dule, Ilaria Barchetta, Flavia Agata Cimini, Giulia Passarella, Arianna Dellanno, Tiziana Filardi, Vittorio Venditti, Enrico Bleve, Diego Bailetti, Elisabetta Romagnoli, Susanna Morano, Marco Giorgio Baroni and Maria Gisella Cavallo

Int. J. Mol. Sci. 2023, 24(7), 6474; https://doi.org/10.3390/ijms24076474 - 30 Mar 2023

Cited by 3 | Viewed by 1504

Abstract

Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk. Our study aimed to explore differences in bone alterations between T2DM women and controls and to assess clinical predictors of bone impairment in T2DM. For this observational case control study, we recruited 126 T2DM female patients and 117 non-diabetic, age- and BMI-comparable women, who underwent clinical examination, routine biochemistry and dual-energy X-ray absorptiometry (DXA) scans for bone mineral density (BMD) and trabecular bone score (TBS) assessment-derived indexes. These were correlated to metabolic parameters, such as glycemic control and lipid profile, by bivariate analyses, and significant variables were entered in multivariate adjusted models to detect independent determinants of altered bone status in diabetes. The T2DM patients were less represented in the normal bone category compared with controls (5% vs. 12%; p = 0.04); T2DM was associated with low TBS (OR: 2.47, C.I. 95%: 1.19–5.16, p = 0.016) in a regression model adjusted for age, menopausal status and BMI. In women with T2DM, TBS directly correlated with plasma high-density lipoprotein cholesterol (HDL-c) (p = 0.029) and vitamin D (p = 0.017) levels. An inverse association was observed with menopausal status (p < 0.001), metabolic syndrome (p = 0.014), BMI (p = 0.005), and waist circumference (p < 0.001). In the multivariate regression analysis, lower HDL-c represented the main predictor of altered bone quality in T2DM, regardless of age, menopausal status, BMI, waist circumference, statin treatment, physical activity, and vitamin D (p = 0.029; R² = 0.47), which likely underlies common pathways between metabolic disease and bone health in diabetes. Full article

(This article belongs to the Special Issue High-Density Lipoproteins in Health and Disease)

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17 pages, 3973 KiB

Open AccessArticle

Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model

by Leonie Schoch, Pablo Sutelman, Rosa Suades, Laura Casani, Teresa Padro, Lina Badimon and Gemma Vilahur

Int. J. Mol. Sci. 2022, 23(15), 8596; https://doi.org/10.3390/ijms23158596 - 02 Aug 2022

Cited by 6 | Viewed by 1526

Abstract

High-density lipoproteins (HDL) undergo adverse remodeling and loss of function in the presence of comorbidities. We assessed the potential of lipid-lowering approaches (diet and rosuvastatin) to rescue hypercholesterolemia-induced HDL dysfunction. Hypercholesterolemia was induced in 32 pigs for 10 days. Then, they randomly received one of the 30-day interventions: (I) hypercholesterolemic (HC) diet; (II) HC diet + rosuvastatin; (III) normocholesterolemic (NC) diet; (IV) NC diet + rosuvastatin. We determined cholesterol efflux capacity (CEC), antioxidant potential, HDL particle number, HDL apolipoprotein content, LDL oxidation, and lipid levels. Hypercholesterolemia time-dependently impaired HDL function (−62% CEC, −11% antioxidant index (AOI); p < 0.01), increased HDL particles numbers 2.8-fold (p < 0.0001), reduced HDL-bound APOM (−23%; p < 0.0001), and increased LDL oxidation 1.7-fold (p < 0.0001). These parameters remained unchanged in animals on HC diet alone up to day 40, while AOI deteriorated up to day 25 (−30%). The switch to NC diet reversed HDL dysfunction, restored apolipoprotein M content and particle numbers, and normalized cholesterol levels at day 40. Rosuvastatin improved HDL, AOI, and apolipoprotein M content. Apolipoprotein A-I and apolipoprotein C-III remained unchanged. Lowering LDL-C levels with a low-fat diet rescues HDL CEC and antioxidant potential, while the addition of rosuvastatin enhances HDL antioxidant capacity in a pig model of hypercholesterolemia. Both strategies restore HDL-bound apolipoprotein M content. Full article

(This article belongs to the Special Issue High-Density Lipoproteins in Health and Disease)

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14 pages, 947 KiB

Open AccessArticle

HDL Cholesterol Efflux and Serum Cholesterol Loading Capacity Alterations Associate to Macrophage Cholesterol Accumulation in FH Patients with Achilles Tendon Xanthoma

by Maria Pia Adorni, Marta Biolo, Francesca Zimetti, Marcella Palumbo, Nicoletta Ronda, Paolo Scarinzi, Paolo Simioni, Maria Giovanna Lupo, Nicola Ferri, Lorenzo Previato, Franco Bernini and Alberto Zambon

Int. J. Mol. Sci. 2022, 23(15), 8255; https://doi.org/10.3390/ijms23158255 - 26 Jul 2022

Cited by 4 | Viewed by 1313

Abstract

Achilles tendon xanthoma (ATX) formation involves macrophage cholesterol accumulation within the tendon, similar to that occurring in atheroma. Macrophage cholesterol homeostasis depends on serum lipoprotein functions, namely the high-density lipoprotein (HDL) capacity to promote cell cholesterol efflux (cholesterol efflux capacity, CEC) and the serum cholesterol loading capacity (CLC). We explored the HDL-CEC and serum CLC, comparing 16 FH patients with ATX to 29 FH patients without ATX. HDL-CEC through the main efflux mechanisms mediated by the transporters ATP binding cassette G1 (ABCG1) and A1 (ABCA1) and the aqueous diffusion (AD) process was determined by a cell-based radioisotopic technique and serum CLC fluorimetrically. Between the two groups, no significant differences were found in terms of plasma lipid profile. A trend toward reduction of cholesterol efflux via AD and a significant increase in ABCA1-mediated HDL-CEC (+18.6%) was observed in ATX compared to no ATX patients. In ATX-presenting patients, ABCG1-mediated HDL-CEC was lower (−11%) and serum CLC was higher (+14%) compared to patients without ATX. Considering all the patients together, ABCG1 HDL-CEC and serum CLC correlated with ATX thickness inversely (p = 0.013) and directly (p < 0.0001), respectively. In conclusion, lipoprotein dysfunctions seem to be involved in ATX physiopathology and progression in FH patients. Full article

(This article belongs to the Special Issue High-Density Lipoproteins in Health and Disease)

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Review

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25 pages, 2320 KiB

Open AccessReview

High-Density Lipoproteins at the Interface between the NLRP3 Inflammasome and Myocardial Infarction

by Helison R. P. Carmo, Isabella Bonilha, Joaquim Barreto, Massimiliano Tognolini, Ilaria Zanotti and Andrei C. Sposito

Int. J. Mol. Sci. 2024, 25(2), 1290; https://doi.org/10.3390/ijms25021290 - 20 Jan 2024

Viewed by 1172

Abstract

Despite significant therapeutic advancements, morbidity and mortality following myocardial infarction (MI) remain unacceptably high. This clinical challenge is primarily attributed to two significant factors: delayed reperfusion and the myocardial injury resulting from coronary reperfusion. Following reperfusion, there is a rapid intracellular pH shift, disruption of ionic balance, heightened oxidative stress, increased activity of proteolytic enzymes, initiation of inflammatory responses, and activation of several cell death pathways, encompassing apoptosis, necroptosis, and pyroptosis. The inflammatory cell death or pyroptosis encompasses the activation of the intracellular multiprotein complex known as the NLRP3 inflammasome. High-density lipoproteins (HDL) are endogenous particles whose components can either promote or mitigate the activation of the NLRP3 inflammasome. In this comprehensive review, we explore the role of inflammasome activation in the context of MI and provide a detailed analysis of how HDL can modulate this process. Full article

(This article belongs to the Special Issue High-Density Lipoproteins in Health and Disease)

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20 pages, 907 KiB

Open AccessReview

HDL Function across the Lifespan: From Childhood, to Pregnancy, to Old Age

by Brian V. Hong, Jingyuan Zheng and Angela M. Zivkovic

Int. J. Mol. Sci. 2023, 24(20), 15305; https://doi.org/10.3390/ijms242015305 - 18 Oct 2023

Cited by 2 | Viewed by 1429

Abstract

The function of high-density lipoprotein (HDL) particles has emerged as a promising therapeutic target and the measurement of HDL function is a promising diagnostic across several disease states. The vast majority of research on HDL functional biology has focused on adult participants with underlying chronic diseases, whereas limited research has investigated the role of HDL in childhood, pregnancy, and old age. Yet, it is apparent that functional HDL is essential at all life stages for maintaining health. In this review, we discuss current data regarding the role of HDL during childhood, pregnancy and in the elderly, how disturbances in HDL may lead to adverse health outcomes, and knowledge gaps in the role of HDL across these life stages. Full article

(This article belongs to the Special Issue High-Density Lipoproteins in Health and Disease)

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19 pages, 1208 KiB

Open AccessReview

Impact of High-Density Lipoproteins on Sepsis

by Bart De Geest and Mudit Mishra

Int. J. Mol. Sci. 2022, 23(21), 12965; https://doi.org/10.3390/ijms232112965 - 26 Oct 2022

Cited by 8 | Viewed by 2875

Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Here, we review the impact of high-density lipoproteins (HDL) on sepsis from the perspective of biochemistry and pathophysiology, epidemiological research, and intervention studies in animals. Pathogen lipid moieties are major ligands for innate immunity receptors, such as toll-like receptors. The binding of pathogen-associated lipids to lipoproteins leads to sequestration, neutralization, and inactivation of their pro-inflammatory effects. Lipoproteins constitute an arm of the innate immune system. Pathogen-associated lipids can be removed from the body via the reverse lipopolysaccharide transport pathway in which HDL play a key role. Independent of the capacity for sequestration, the direct anti-inflammatory effects of HDL may counteract the development of sepsis. Mendelian randomization research using genetic variants associated with HDL cholesterol as an instrumental variable was consistent with a probable causal relationship between increased HDL cholesterol levels and decreased risk of infectious hospitalizations. Low HDL cholesterol independently predicts an adverse prognosis in sepsis both in observational epidemiology and in Mendelian randomization studies. Several HDL-associated enzymes, including phospholipid transfer protein (PLTP) and cholesterol ester transfer protein (CETP), undergo profound changes during sepsis. Potential HDL-directed interventions for treatment of sepsis include apolipoprotein A-I-based therapies, recombinant PLTP, and CETP inhibition. Full article

(This article belongs to the Special Issue High-Density Lipoproteins in Health and Disease)

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