Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
3.7
4.7
Journals
Biomedicines
Special Issues
High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and...
share announcement

High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 30987

Special Issue Editors

Dr. Joan Carles Escolà-Gil

E-Mail Website
Guest Editor
Institut d’Investigacions Biomèdiques (IIB) Sant Pau, CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
Interests: atherosclerosis; cholesterol; genetically-modified mice; HDL; lipoproteins
Special Issues, Collections and Topics in MDPI journals
Dr. Josep Julve

E-Mail Website
Guest Editor
1. Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau–Centre CERCA, Barcelona, Spain
2. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
Interests: obesity; diabetes; lipoprotein metabolism; metabolic syndrome; therapeutics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Clinical and experimental studies have shown that low levels of plasma high-density lipoprotein (HDL) cholesterol are associated with increased atherosclerotic cardiovascular disease. Nevertheless, HDL-targeted drugs such as cholesteryl ester transfer protein inhibitors, fibrates, and niacin have failed to reduce cardiovascular events in clinical trials, thereby casting doubt on the beneficial effects of raising HDL levels.

Experimental studies have identified several cardioprotective functions of HDL, including the enhancement of macrophage reverse cholesterol transport and endothelial function, as well as its antioxidant, anti-inflammatory, and anti-thrombotic properties. HDL is highly heterogeneous and carries a large variety of lipids, proteins, and microRNAs. The different composition of HDL subpopulations is directly related to their cardioprotective functions, but the assignment of specific molecules to HDL functions is not completely understood.

Compelling available data strongly indicate that increased HDL cholesterol levels do not always correlate with enhanced beneficial HDL properties, thus questioning their potential as a biomarker of HDL functionality. In addition, the association between low HDL cholesterol and cardiovascular disease can be further confounded by several factors, including insulin resistance, inflammation, and/or metabolic derangements leading to altered plasma lipids, thereby indicating that low HDL levels could simply be a marker of an underlying pathology. Current research is moving towards both the development of robust HDL function tests and the identification of specific HDL molecules (many of them bioactive) within HDL that can be widely applied in translational and pre-clinical studies. The application of novel HDL-based approaches for therapeutic purposes requires the development of validated and reproducible measures of these key atheroprotective HDL functions.

Dr. Joan Carles Escolà-Gil
Dr. Josep Julve
Guest Editors

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. Biomedicines 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 2600 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.

Keywords

  • atherosclerosis
  • cardiovascular
  • diabetes
  • cholesterol
  • HDL
  • inflammation
  • mice
  • oxidation
  • therapy

Related Special Issues

Published Papers (10 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

4 pages, 209 KiB  
Editorial
High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II
by Josep Julve and Joan Carles Escolà-Gil
Biomedicines 2022, 10(3), 620; https://doi.org/10.3390/biomedicines10030620 - 07 Mar 2022
Cited by 1 | Viewed by 1525
Abstract
The notion that high-density lipoproteins (HDL) are atheroprotective is supported by different lines of evidence [...] Full article
(This article belongs to the Special Issue High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II)

Research

Jump to: Editorial, Review

12 pages, 847 KiB  
Article
The Capacity of APOB-Depleted Plasma in Inducing ATP-Binding Cassette A1/G1-Mediated Macrophage Cholesterol Efflux—But Not Gut Microbial-Derived Metabolites—Is Independently Associated with Mortality in Patients with ST-Segment Elevation Myocardial Infarction
by Marina Canyelles, Álvaro García-Osuna, Alexandra Junza, Oscar Yanes, Núria Puig, Jordi Ordóñez-Llanos, Alessandro Sionis, Jordi Sans-Roselló, Aitor Alquézar-Arbé, David Santos, Noemi Rotllan, Josep Julve, Mireia Tondo, Joan Carles Escolà-Gil and Francisco Blanco-Vaca
Biomedicines 2021, 9(10), 1336; https://doi.org/10.3390/biomedicines9101336 - 27 Sep 2021
Cited by 3 | Viewed by 1992
Abstract
Impaired HDL-mediated macrophage cholesterol efflux and higher circulating concentrations of trimethylamine N-oxide (TMAO) levels are independent risk factors for cardiovascular mortality. The TMAO precursors, γ-butyrobetaine (γBB) and Trimethyllysine (TML), have also been recently associated with cardiovascular death, but their interactions with HDL-mediated cholesterol [...] Read more.
Impaired HDL-mediated macrophage cholesterol efflux and higher circulating concentrations of trimethylamine N-oxide (TMAO) levels are independent risk factors for cardiovascular mortality. The TMAO precursors, γ-butyrobetaine (γBB) and Trimethyllysine (TML), have also been recently associated with cardiovascular death, but their interactions with HDL-mediated cholesterol efflux remain unclear. We aimed to determine the associations between APOB depleted plasma-mediated macrophage cholesterol efflux and plasma TMAO, γBB, and TML concentrations and explore their association with two-year follow-up mortality in patients with acute ST-elevation myocardial infarction (STEMI) and unstable angina (UA). Baseline and ATP-binding cassette transporter ABCA1 and ABCG1 (ABCA1/G1)-mediated macrophage cholesterol efflux to APOB-depleted plasma was decreased in patients with STEMI, and the latter was further impaired in those who died during follow-up. Moreover, the circulating concentrations of TMAO, γBB, and TML were higher in the deceased STEMI patients when compared with the STEMI survivors or UA patients. However, after statistical adjustment, only ABCA1/G1-mediated macrophage cholesterol efflux remained significantly associated with mortality. Furthermore, neither the TMAO, γBB, nor TML levels altered the HDL-mediated macrophage cholesterol efflux in vitro. We conclude that impaired ABCA1/G1-mediated macrophage cholesterol efflux is independently associated with mortality at follow-up in STEMI patients. Full article
(This article belongs to the Special Issue High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II)
►▼ Show Figures

Figure 1

17 pages, 6216 KiB  
Article
Apolipoprotein Signature of HDL and LDL from Atherosclerotic Patients in Relation with Carotid Plaque Typology: A Preliminary Report
by Francesco Finamore, Gabriele Nieddu, Silvia Rocchiccioli, Rita Spirito, Anna Guarino, Marilena Formato and Antonio Junior Lepedda
Biomedicines 2021, 9(9), 1156; https://doi.org/10.3390/biomedicines9091156 - 03 Sep 2021
Cited by 3 | Viewed by 2062
Abstract
In the past years, it has become increasingly clear that the protein cargo of the different lipoprotein classes is largely responsible for carrying out their various functions, also in relation to pathological conditions, including atherosclerosis. Accordingly, detailed information about their apolipoprotein composition and [...] Read more.
In the past years, it has become increasingly clear that the protein cargo of the different lipoprotein classes is largely responsible for carrying out their various functions, also in relation to pathological conditions, including atherosclerosis. Accordingly, detailed information about their apolipoprotein composition and structure may contribute to the revelation of their role in atherogenesis and the understanding of the mechanisms that lead to atherosclerotic degeneration and toward vulnerable plaque formation. With this aim, shotgun proteomics was applied to identify the apolipoprotein signatures of both high-density and low-density lipoproteins (HDL and LDL) plasma fractions purified from healthy volunteers and atherosclerotic patients with different plaque typologies who underwent carotid endarterectomy. By this approach, two proteins with potential implications in inflammatory, immune, and hemostatic pathways, namely, integrin beta-2 (P05107) and secretoglobin family 3A member 2 (Q96PL1), have been confirmed to belong to the HDL proteome. Similarly, the list of LDL-associated proteins has been enriched with 21 proteins involved in complement and coagulation cascades and the acute-phase response, which potentially double the protein species of LDL cargo. Moreover, differential expression analysis has shown protein signatures specific for patients with “hard” or “soft” plaques. Full article
(This article belongs to the Special Issue High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial, Research

15 pages, 618 KiB  
Review
HDL Is Not Dead Yet
by Shuhui Wang Lorkowski and Jonathan D. Smith
Biomedicines 2022, 10(1), 128; https://doi.org/10.3390/biomedicines10010128 - 07 Jan 2022
Cited by 8 | Viewed by 2860
Abstract
High-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with coronary heart disease (CHD) in multiple epidemiological studies, but whether HDL is causal or merely associated with CHD is unclear. Recent trials for HDL-raising drugs were either not effective in reducing CHD events or, [...] Read more.
High-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with coronary heart disease (CHD) in multiple epidemiological studies, but whether HDL is causal or merely associated with CHD is unclear. Recent trials for HDL-raising drugs were either not effective in reducing CHD events or, if beneficial in reducing CHD events, were not conclusive as the findings could be attributed to the drugs’ LDL-reducing activity. Furthermore, the first large Mendelian randomization study did not causally relate HDL-C levels to decreased CHD. Thus, the hypothesis that HDL is protective against CHD has been rightfully challenged. However, subsequent Mendelian randomization studies found HDL characteristics that are causally related to decreased CHD. Many aspects of HDL structure and function, especially in reverse cholesterol transport, may be better indicators of HDL’s protective activity than simply measuring HDL-C. Cholesterol efflux capacity is associated with lower levels of prevalent and incident CHD, even after adjustment for HDL-C and apolipoprotein A-1 levels. Also, subjects with very high levels of HDL-C, including those with rare mutations that disrupt hepatic HDL uptake and reverse cholesterol transport, may be at higher risk for CHD than those with moderate levels. We describe here several cell-based and cell-free in vitro assays of HDL structure and function that may be used in clinical studies to determine which of HDL’s functions are best associated with protection against CHD. We conclude that the HDL hypothesis may need revision based on studies of HDL structure and function, but that the HDL hypothesis is not dead yet. Full article
(This article belongs to the Special Issue High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II)
►▼ Show Figures

Figure 1

13 pages, 1092 KiB  
Review
High-Density Lipoprotein Subfractions: Much Ado about Nothing or Clinically Important?
by Knut Tore Lappegård, Christian Abendstein Kjellmo and Anders Hovland
Biomedicines 2021, 9(7), 836; https://doi.org/10.3390/biomedicines9070836 - 18 Jul 2021
Cited by 11 | Viewed by 3166
Abstract
High-density lipoproteins (HDL) are a heterogenous group of plasma molecules with a large variety in composition. There is a wide specter in lipid content and the number of different proteins that has been associated with HDL is approaching 100. Given this heterogeneity and [...] Read more.
High-density lipoproteins (HDL) are a heterogenous group of plasma molecules with a large variety in composition. There is a wide specter in lipid content and the number of different proteins that has been associated with HDL is approaching 100. Given this heterogeneity and the fact that the total amount of HDL is inversely related to the risk of coronary heart disease (CHD), there has been increasing interest in the function of specific HDL subgroups and in what way measuring and quantifying these subgroups could be of clinical importance in determining individual CHD risk. If certain subgroups appear to be more protective than others, it may also in the future be possible to pharmacologically increase beneficial and decrease harmful subgroups in order to reduce CHD risk. In this review we give a short historical perspective, summarize some of the recent clinical findings regarding HDL subclassifications and discuss why such classification may or may not be of clinical relevance. Full article
(This article belongs to the Special Issue High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II)
►▼ Show Figures

Figure 1

11 pages, 19491 KiB  
Review
Familial Hypercholesterolemia: Do HDL Play a Role?
by Juan Pedro-Botet, Elisenda Climent and David Benaiges
Biomedicines 2021, 9(7), 810; https://doi.org/10.3390/biomedicines9070810 - 13 Jul 2021
Cited by 12 | Viewed by 2896
Abstract
Cardiovascular disease (CVD) in heterozygous familial hypercholesterolemia (HeFH), the most frequent monogenic disorder of human metabolism, is largely driven by low-density lipoprotein (LDL) cholesterol concentrations. Since the CVD rate differs considerably in this population, beyond the lifetime LDL cholesterol vascular accumulation, other classical [...] Read more.
Cardiovascular disease (CVD) in heterozygous familial hypercholesterolemia (HeFH), the most frequent monogenic disorder of human metabolism, is largely driven by low-density lipoprotein (LDL) cholesterol concentrations. Since the CVD rate differs considerably in this population, beyond the lifetime LDL cholesterol vascular accumulation, other classical risk factors are involved in the high cardiovascular risk of HeFH. Among other lipoprotein disturbances, alterations in the phenotype and functionality of high-density lipoproteins (HDL) have been described in HeFH patients, contributing to the presence and severity of CVD. In fact, HDL are the first defensive barrier against the burden of high LDL cholesterol levels owing to their contribution to reverse cholesterol transport as well as their antioxidant and anti-inflammatory properties, among others. In this context, the present narrative review aimed to focus on quantitative and qualitative abnormalities in HDL particles in HeFH, encompassing metabolic, genetic and epigenetic aspects. Full article
(This article belongs to the Special Issue High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II)
►▼ Show Figures

Graphical abstract

14 pages, 835 KiB  
Review
HDL Dysfunctionality: Clinical Relevance of Quality Rather Than Quantity
by Arianna Bonizzi, Gabriele Piuri, Fabio Corsi, Roberta Cazzola and Serena Mazzucchelli
Biomedicines 2021, 9(7), 729; https://doi.org/10.3390/biomedicines9070729 - 25 Jun 2021
Cited by 22 | Viewed by 3470
Abstract
High-density lipoproteins (HDLs) represent a class of lipoproteins very heterogeneous in structure, composition, and biological functions, which carry out reverse cholesterol transport, antioxidant, anti-inflammatory, antithrombotic, and vasodilator actions. Despite the evidence suggesting a clear inverse relationship between HDL cholesterol (HDL-c) concentration and the [...] Read more.
High-density lipoproteins (HDLs) represent a class of lipoproteins very heterogeneous in structure, composition, and biological functions, which carry out reverse cholesterol transport, antioxidant, anti-inflammatory, antithrombotic, and vasodilator actions. Despite the evidence suggesting a clear inverse relationship between HDL cholesterol (HDL-c) concentration and the risk for cardiovascular disease, plasma HDL cholesterol levels do not predict the functionality and composition of HDLs. The importance of defining both the amount of cholesterol transported and lipoprotein functionality has recently been highlighted. Indeed, different clinical conditions such as obesity, diabetes mellitus type 2 (T2DM), and cardiovascular disease (CVD) can alter the HDL functionality, converting normal HDLs into dysfunctional ones, undergoing structural changes, and exhibiting proinflammatory, pro-oxidant, prothrombotic, and proapoptotic properties. The aim of the current review is to summarize the actual knowledge concerning the physical–chemical alteration of HDLs related to their functions, which have been found to be relevant in several pathological conditions associated with systemic inflammation and oxidative stress. Full article
(This article belongs to the Special Issue High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II)
►▼ Show Figures

Graphical abstract

14 pages, 1299 KiB  
Review
Structure and Dynamics of Oxidized Lipoproteins In Vivo: Roles of High-Density Lipoprotein
by Hiroyuki Itabe, Naoko Sawada, Tomohiko Makiyama and Takashi Obama
Biomedicines 2021, 9(6), 655; https://doi.org/10.3390/biomedicines9060655 - 08 Jun 2021
Cited by 15 | Viewed by 3440
Abstract
Oxidative modification of lipoproteins is implicated in the occurrence and development of atherosclerotic lesions. Earlier studies have elucidated on the mechanisms of foam cell formation and lipid accumulation in these lesions, which is mediated by scavenger receptor-mediated endocytosis of oxidized low-density lipoprotein (oxLDL). [...] Read more.
Oxidative modification of lipoproteins is implicated in the occurrence and development of atherosclerotic lesions. Earlier studies have elucidated on the mechanisms of foam cell formation and lipid accumulation in these lesions, which is mediated by scavenger receptor-mediated endocytosis of oxidized low-density lipoprotein (oxLDL). Mounting clinical evidence has supported the involvement of oxLDL in cardiovascular diseases. High-density lipoprotein (HDL) is known as anti-atherogenic; however, recent studies have shown circulating oxidized HDL (oxHDL) is related to cardiovascular diseases. A modified structure of oxLDL, which was increased in the plasma of patients with acute myocardial infarction, was characterized. It had two unique features: (1) a fraction of oxLDL accompanied oxHDL, and (2) apoA1 was heavily modified, while modification of apoB, and the accumulation of oxidized phosphatidylcholine (oxPC) and lysophosphatidylcholine (lysoPC) was less pronounced. When LDL and HDL were present at the same time, oxidized lipoproteins actively interacted with each other, and oxPC and lysoPC were transferred to another lipoprotein particle and enzymatically metabolized rapidly. This brief review provides a novel view on the dynamics of oxLDL and oxHDL in circulation. Full article
(This article belongs to the Special Issue High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II)
►▼ Show Figures

Graphical abstract

14 pages, 724 KiB  
Review
Subpopulations of High-Density Lipoprotein: Friends or Foes in Cardiovascular Disease Risk in Chronic Kidney Disease?
by Susana Coimbra, Flávio Reis, Maria João Valente, Susana Rocha, Cristina Catarino, Petronila Rocha-Pereira, Maria Sameiro-Faria, Elsa Bronze-da-Rocha, Luís Belo and Alice Santos-Silva
Biomedicines 2021, 9(5), 554; https://doi.org/10.3390/biomedicines9050554 - 16 May 2021
Cited by 2 | Viewed by 3264
Abstract
Dyslipidemia is a major traditional risk factor for cardiovascular disease (CVD) in chronic kidney disease (CKD) patients, although the altered lipid profile does not explain the number and severity of CVD events. High-density lipoprotein (HDL) is a heterogeneous (size, composition, and functionality) population [...] Read more.
Dyslipidemia is a major traditional risk factor for cardiovascular disease (CVD) in chronic kidney disease (CKD) patients, although the altered lipid profile does not explain the number and severity of CVD events. High-density lipoprotein (HDL) is a heterogeneous (size, composition, and functionality) population of particles with different atherogenic or atheroprotective properties. HDL-cholesterol concentrations per se may not entirely reflect a beneficial or a risk profile for CVD. Large HDL in CKD patients may have a unique proteome and lipid composition, impairing their cholesterol efflux capacity. This lack of HDL functionality may contribute to the paradoxical coexistence of increased large HDL and enhanced risk for CVD events. Moreover, CKD is associated with inflammation, oxidative stress, diabetes, and/or hypertension that are able to interfere with the anti-inflammatory, antioxidative, and antithrombotic properties of HDL subpopulations. How these changes interfere with HDL functions in CKD is still poorly understood. Further studies are warranted to fully clarify if different HDL subpopulations present different functionalities and/or atheroprotective effects. To achieve this goal, the standardization of techniques would be valuable. Full article
(This article belongs to the Special Issue High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II)
►▼ Show Figures

Figure 1

22 pages, 1387 KiB  
Review
Fetal High-Density Lipoproteins: Current Knowledge on Particle Metabolism, Composition and Function in Health and Disease
by Julia T. Stadler, Christian Wadsack and Gunther Marsche
Biomedicines 2021, 9(4), 349; https://doi.org/10.3390/biomedicines9040349 - 30 Mar 2021
Cited by 15 | Viewed by 4492
Abstract
Cholesterol and other lipids carried by lipoproteins play an indispensable role in fetal development. Recent evidence suggests that maternally derived high-density lipoprotein (HDL) differs from fetal HDL with respect to its proteome, size, and function. Compared to the HDL of adults, fetal HDL [...] Read more.
Cholesterol and other lipids carried by lipoproteins play an indispensable role in fetal development. Recent evidence suggests that maternally derived high-density lipoprotein (HDL) differs from fetal HDL with respect to its proteome, size, and function. Compared to the HDL of adults, fetal HDL is the major carrier of cholesterol and has a unique composition that implies other physiological functions. Fetal HDL is enriched in apolipoprotein E, which binds with high affinity to the low-density lipoprotein receptor. Thus, it appears that a primary function of fetal HDL is the transport of cholesterol to tissues as is accomplished by low-density lipoproteins in adults. The fetal HDL-associated bioactive sphingolipid sphingosine-1-phosphate shows strong vasoprotective effects at the fetoplacental vasculature. Moreover, lipoprotein-associated phospholipase A2 carried by fetal-HDL exerts anti-oxidative and athero-protective functions on the fetoplacental endothelium. Notably, the mass and activity of HDL-associated paraoxonase 1 are about 5-fold lower in the fetus, accompanied by an attenuation of anti-oxidative activity of fetal HDL. Cholesteryl ester transfer protein activity is reduced in fetal circulation despite similar amounts of the enzyme in maternal and fetal serum. This review summarizes the current knowledge on fetal HDL as a potential vasoprotective lipoprotein during fetal development. We also provide an overview of whether and how the protective functionalities of HDL are impaired in pregnancy-related syndromes such as pre-eclampsia or gestational diabetes mellitus. Full article
(This article belongs to the Special Issue High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-10
Back to TopTop