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Article ; Online: HDL as a Treatment Target: Should We Abandon This Idea?

Begue, Floran / Apalama, Marie Laurine / Lambert, Gilles / Meilhac, Olivier

2023 Volume 25, Issue 12, Page(s) 1093–1099

Abstract: Purpose of review: High-density lipoproteins (HDL) have long been regarded as an antiatherogenic lipoprotein species by virtue of their role in reverse cholesterol transport (RCT), as well as their established anti-inflammatory and antioxidant ... ...

Abstract	Purpose of review: High-density lipoproteins (HDL) have long been regarded as an antiatherogenic lipoprotein species by virtue of their role in reverse cholesterol transport (RCT), as well as their established anti-inflammatory and antioxidant properties. For decades, HDL have been an extremely appealing therapeutic target to combat atherosclerotic cardiovascular diseases (ASCVD). Recent findings: Unfortunately, neither increasing HDL with drugs nor direct infusions of reconstituted HDL have convincedly proven to be positive strategies for cardiovascular health, raising the question of whether we should abandon the idea of considering HDL as a treatment target. The results of two large clinical trials, one testing the latest CETP inhibitor Obicetrapib and the other testing the infusion of patients post-acute coronary events with reconstituted HDL, are still awaited. If they prove negative, these trials will seal the fate of HDL as a direct therapeutic target. However, using HDL as a therapeutic agent still holds promise if we manage to optimize their beneficial properties for not only ASCVD but also outside the cardiovascular field.
MeSH term(s)	Humans ; Lipoproteins, HDL ; Cholesterol, HDL/metabolism ; Atherosclerosis/drug therapy ; Biological Transport ; Cardiovascular Diseases/prevention & control ; Cardiovascular Diseases/drug therapy
Chemical Substances	Lipoproteins, HDL ; Cholesterol, HDL
Language	English
Publishing date	2023-12-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057369-8
ISSN	1534-6242 ; 1523-3804
ISSN (online)	1534-6242
ISSN	1523-3804
DOI	10.1007/s11883-023-01176-1
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Article ; Online: Plasma Apolipoprotein Concentrations Are Highly Altered in Severe Intensive Care Unit COVID-19 Patients: Preliminary Results from the LIPICOR Cohort Study.

Begue, Floran / Chemello, Kévin / Veeren, Bryan / Lortat-Jacob, Brice / Tran-Dinh, Alexy / Zappella, Nathalie / Snauwaert, Aurelie / Robert, Tiphaine / Rondeau, Philippe / Lagrange-Xelot, Marie / Montravers, Philippe / Couret, David / Tanaka, Sébastien / Meilhac, Olivier

International journal of molecular sciences

2023 Volume 24, Issue 5

Abstract: SARS-CoV-2 infection goes beyond acute pneumonia, as it also impacts lipid metabolism. Decreased HDL-C and LDL-C levels have been reported in patients with COVID-19. The lipid profile is a less robust biochemical marker than apolipoproteins, components ... ...

Abstract	SARS-CoV-2 infection goes beyond acute pneumonia, as it also impacts lipid metabolism. Decreased HDL-C and LDL-C levels have been reported in patients with COVID-19. The lipid profile is a less robust biochemical marker than apolipoproteins, components of lipoproteins. However, the association of apolipoprotein levels during COVID-19 is not well described and understood. The objective of our study is to measure plasma levels of 14 apolipoproteins in patients with COVID-19 and to evaluate the relationships between apolipoprotein levels, severity factors and patient outcomes. From November to March 2021, 44 patients were recruited on admission to the intensive care unit because of COVID-19. Fourteen apolipoproteins and LCAT were measured by LC-MS/MS in plasma of 44 COVID-19 patients on admission to the ICU and 44 healthy control subjects. Absolute apolipoprotein concentrations were compared between COVID-19 patients and controls. Plasma apolipoproteins (Apo) A (I, II, IV), C(I, II), D, H, J and M and LCAT were lower in COVID-19 patients, whereas Apo E was higher. COVID-19 severity factors such as PaO2/FiO2 ratio, SO-FA score and CRP were correlated with certain apolipoproteins. Lower Apo B100 and LCAT levels were observed in non-survivors of COVID-19 versus survivors. To conclude, in this study, lipid and apolipoprotein profiles are altered in COVID-19 patients. Low Apo B100 and LCAT levels may be predictive of non-survival in COVID-19 patients.
MeSH term(s)	Humans ; Cohort Studies ; Chromatography, Liquid ; Cholesterol/metabolism ; COVID-19 ; SARS-CoV-2/metabolism ; Tandem Mass Spectrometry ; Apolipoproteins ; Apolipoproteins A ; Apolipoprotein B-100 ; Intensive Care Units ; Apolipoprotein A-I ; Apolipoproteins B ; Apolipoprotein A-II
Chemical Substances	Cholesterol (97C5T2UQ7J) ; Apolipoproteins ; Apolipoproteins A ; Apolipoprotein B-100 ; Apolipoprotein A-I ; Apolipoproteins B ; Apolipoprotein A-II
Language	English
Publishing date	2023-02-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24054605
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Article: Zika E Glycan Loop Region and Guillain-Barré Syndrome-Related Proteins: A Possible Molecular Mimicry to Be Taken in Account for Vaccine Development.

Lebeau, Grégorie / Frumence, Etienne / Turpin, Jonathan / Begue, Floran / Hoarau, Jean-Jacques / Gadea, Gilles / Krejbich-Trotot, Pascale / Desprès, Philippe / Viranaicken, Wildriss

Vaccines

2021 Volume 9, Issue 3

Abstract: The neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of ... ...

Abstract	The neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of the ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. The analysis of the ZIKV epidemic strains showed that the glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Ca
Language	English
Publishing date	2021-03-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines9030283
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Article ; Online: Extracellular Vesicles Are Conveyors of the NS1 Toxin during Dengue Virus and Zika Virus Infection.

Safadi, Daed El / Lebeau, Grégorie / Lagrave, Alisé / Mélade, Julien / Grondin, Lauriane / Rosanaly, Sarah / Begue, Floran / Hoareau, Mathilde / Veeren, Bryan / Roche, Marjolaine / Hoarau, Jean-Jacques / Meilhac, Olivier / Mavingui, Patrick / Desprès, Philippe / Viranaïcken, Wildriss / Krejbich-Trotot, Pascale

Viruses

2023 Volume 15, Issue 2

Abstract: Extracellular vesicles (EVs), produced during viral infections, are of emerging interest in understanding infectious processes and host-pathogen interactions. EVs and exosomes in particular have the natural ability to transport nucleic acids, proteins, ... ...

Abstract	Extracellular vesicles (EVs), produced during viral infections, are of emerging interest in understanding infectious processes and host-pathogen interactions. EVs and exosomes in particular have the natural ability to transport nucleic acids, proteins, and other components of cellular or viral origin. Thus, they participate in intercellular communication, immune responses, and infectious and pathophysiological processes. Some viruses are known to hijack the cell production and content of EVs for their benefit. Here, we investigate whether two pathogenic flaviviruses i.e., Zika Virus (ZIKV) and Dengue virus (DENV2) could have an impact on the features of EVs. The analysis of EVs produced by infected cells allowed us to identify that the non-structural protein 1 (NS1), described as a viral toxin, is associated with exosomes. This observation could be confirmed under conditions of overexpression of recombinant NS1 from each flavivirus. Using different isolation methods (i.e., exosome isolation kit, size exclusion chromatography, Polyethylene Glycol enrichment, and ELISA capture), we showed that NS1 was present as a dimer at the surface of excreted exosomes, and that this association could occur in the extracellular compartment. This finding could be of major importance in a physiological context. Indeed, this capacity of NS1 to address EVs and its implication in the pathophysiology during Dengue or Zika diseases should be explored. Furthermore, exosomes that have demonstrated a natural capacity to vectorize NS1 could serve as useful tools for vaccine development.
MeSH term(s)	Humans ; Dengue Virus ; Exosomes ; Extracellular Vesicles ; Zika Virus ; Zika Virus Infection ; Viral Nonstructural Proteins/metabolism
Chemical Substances	NS1 protein, zika virus ; Viral Nonstructural Proteins
Language	English
Publishing date	2023-01-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15020364
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Article ; Online: Zika E Glycan Loop Region and Guillain–Barré Syndrome-Related Proteins

Grégorie Lebeau / Etienne Frumence / Jonathan Turpin / Floran Begue / Jean-Jacques Hoarau / Gilles Gadea / Pascale Krejbich-Trotot / Philippe Desprès / Wildriss Viranaicken

Vaccines, Vol 9, Iss 283, p

A Possible Molecular Mimicry to Be Taken in Account for Vaccine Development

2021 Volume 283

Abstract: The neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain–Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of ... ...

Abstract	The neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain–Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of the ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. The analysis of the ZIKV epidemic strains showed that the glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Ca v 1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our in silico analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS through a potent mimicry with Heat Shock 70 kDa protein 12A (HSP70 12A).
Keywords	ZIKV ; Guillain–Barré syndrome ; molecular mimicry ; calcium channel voltage dependent ; heat shock protein ; vaccine ; Medicine ; R
Subject code	572
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: First Recombinant High-Density Lipoprotein Particles Administration in a Severe ICU COVID-19 Patient, a Multi-Omics Exploratory Investigation.

Tanaka, Sébastien / Begue, Floran / Veeren, Bryan / Tran-Dinh, Alexy / Robert, Tiphaine / Tashk, Parvine / Lortat-Jacob, Brice / Faille, Dorothée / de Chaisemartin, Luc / Zappella, Nathalie / Atchade, Enora / Kramer, Laura / Montravers, Philippe / Meilhac, Olivier

Biomedicines

2022 Volume 10, Issue 4

Abstract: High-density lipoproteins (HDLs) have multiple endothelioprotective properties. During SARS-CoV-2 infection, HDL-cholesterol (HDL-C) concentration is markedly reduced, and studies have described severe impairment of the functionality of HDL particles. ... ...

Abstract	High-density lipoproteins (HDLs) have multiple endothelioprotective properties. During SARS-CoV-2 infection, HDL-cholesterol (HDL-C) concentration is markedly reduced, and studies have described severe impairment of the functionality of HDL particles. Here, we report a multi-omic investigation of the first administration of recombinant HDL (rHDL) particles in a severe COVID-19 patient in an intensive care unit. Plasma ApoA1 increased and HDL-C decreased after each recombinant HDL injection, suggesting that these particles were functional in terms of reverse cholesterol transport. The proportion of large HDL particles also increased after injection of recombinant HDL. Shotgun proteomics performed on HDLs isolated by ultracentrifugation indicated that ApoA1 was more abundant after injections whereas most of the pro-inflammatory proteins identified were less abundant. Assessment of Serum amyloid A-1, inflammatory markers, and cytokines showed a significant decrease for most of them during recombinant HDL infusion. Our results suggest that recombinant HDL infusion is feasible and a potential therapeutic strategy to be explored in COVID-19 patients.
Language	English
Publishing date	2022-03-23
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10040754
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Article: Antirhea borbonica

Delveaux, Jade / Turpin, Chloé / Veeren, Bryan / Diotel, Nicolas / Bravo, Susana B / Begue, Floran / Álvarez, Ezequiel / Meilhac, Olivier / Bourdon, Emmanuel / Rondeau, Philippe

Antioxidants (Basel, Switzerland)

2020 Volume 9, Issue 5

Abstract: Diabetes constitutes a major health problem associated with severe complications. In hyperglycemic conditions, chronically increased oxidation and glycation of circulating components lead to advanced glycation end-products (AGEs) formation, a key ... ...

Abstract	Diabetes constitutes a major health problem associated with severe complications. In hyperglycemic conditions, chronically increased oxidation and glycation of circulating components lead to advanced glycation end-products (AGEs) formation, a key contributor in diabetes complication progression. In line with literature documenting the beneficial properties of herbal teas, this study evaluates the antioxidant/glycant properties of
Language	English
Publishing date	2020-05-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox9050415
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Altered high-density lipoprotein composition and functions during severe COVID-19.

Begue, Floran / Tanaka, Sébastien / Mouktadi, Zarouki / Rondeau, Philippe / Veeren, Bryan / Diotel, Nicolas / Tran-Dinh, Alexy / Robert, Tiphaine / Vélia, Erick / Mavingui, Patrick / Lagrange-Xélot, Marie / Montravers, Philippe / Couret, David / Meilhac, Olivier

Scientific reports

2021 Volume 11, Issue 1, Page(s) 2291

Abstract: Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported ...

Abstract	Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.
MeSH term(s)	Apolipoprotein A-I/blood ; Aryldialkylphosphatase/analysis ; Aryldialkylphosphatase/blood ; COVID-19/blood ; COVID-19/epidemiology ; COVID-19/pathology ; COVID-19/virology ; Case-Control Studies ; Chromatography, Liquid/methods ; Endothelial Cells/pathology ; Female ; France/epidemiology ; Humans ; Lipoproteins, HDL/blood ; Male ; Middle Aged ; Pandemics ; Proteome/metabolism ; Proteomics/methods ; SARS-CoV-2/isolation & purification ; Serum Amyloid A Protein/metabolism ; Tandem Mass Spectrometry/methods ; Tumor Necrosis Factor-alpha/blood ; alpha 1-Antitrypsin/blood
Chemical Substances	Apolipoprotein A-I ; Lipoproteins, HDL ; Proteome ; Serum Amyloid A Protein ; Tumor Necrosis Factor-alpha ; alpha 1-Antitrypsin ; Aryldialkylphosphatase (EC 3.1.8.1)
Language	English
Publishing date	2021-01-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-81638-1
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Article ; Online: Altered high-density lipoprotein composition and functions during severe COVID-19

Floran Begue / Sébastien Tanaka / Zarouki Mouktadi / Philippe Rondeau / Bryan Veeren / Nicolas Diotel / Alexy Tran-Dinh / Tiphaine Robert / Erick Vélia / Patrick Mavingui / Marie Lagrange-Xélot / Philippe Montravers / David Couret / Olivier Meilhac

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 16

Abstract: Abstract Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were ...

Abstract	Abstract Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Antirhea borbonica Aqueous Extract Protects Albumin and Erythrocytes from Glycoxidative Damages

Delveaux, Jade / Turpin, Chloé / Veeren, Bryan / Diotel, Nicolas / Bravo, Susana B / Begue, Floran / Álvarez, Ezequiel / Meilhac, Olivier / Bourdon, Emmanuel / Rondeau, Philippe

Antioxidants. 2020 May 12, v. 9, no. 5

2020

Abstract	Diabetes constitutes a major health problem associated with severe complications. In hyperglycemic conditions, chronically increased oxidation and glycation of circulating components lead to advanced glycation end-products (AGEs) formation, a key contributor in diabetes complication progression. In line with literature documenting the beneficial properties of herbal teas, this study evaluates the antioxidant/glycant properties of Antirhea borbonica (Ab). Ab aqueous extract effects were tested on human albumin or erythrocytes submitted to methyl glyoxal-mediated glycoxidative damages. By using mass spectrometry, Ab aqueous extracts revealed to be rich in polyphenols. All tested biomarkers of oxidation and glycation, such as AGE, ketoamine, oxidized thiol groups, were decreased in albumin when glycated in the presence of Ab aqueous extract. Ab extract preserve erythrocyte from methylglyoxal (MGO)-induced damages in terms of restored membrane deformability, reduced oxidative stress and eryptosis phenomenon. Antioxidant capacities of Ab extract on erythrocytes were retrieved in vivo in zebrafish previously infused with MGO. These results bring new evidences on the deleterious impacts of glycation on albumin and erythrocyte in diabetes. Furthermore, it reveals antioxidant and antiglycant properties of Ab that could be used for the dietary modulation of oxidative stress and glycation in hyperglycemic situations.
Keywords	Danio rerio ; advanced glycation end products ; albumins ; antioxidant activity ; antioxidants ; biomarkers ; diabetic complications ; erythrocytes ; glycation ; herbal tea ; humans ; mass spectrometry ; oxidation ; oxidative stress ; polyphenols ; thiols
Language	English
Dates of publication	2020-0512
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox9050415
Database	NAL-Catalogue (AGRICOLA)

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