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Article: Oxysterols in Vascular Cells and Role in Atherosclerosis.

Luquain-Costaz, Celine / Delton, Isabelle

Advances in experimental medicine and biology

2023 Volume 1440, Page(s) 213–229

Abstract: Atherosclerosis is a major cardiovascular complication of diseases associated with elevated oxidative stress such as type 2 diabetes and metabolic syndrome. In these situations, low-density lipoproteins (LDL) undergo oxidation. Oxidized LDL displays ... ...

Abstract	Atherosclerosis is a major cardiovascular complication of diseases associated with elevated oxidative stress such as type 2 diabetes and metabolic syndrome. In these situations, low-density lipoproteins (LDL) undergo oxidation. Oxidized LDL displays proatherogenic activities through multiple and complex mechanisms which lead to dysfunctions of vascular cells (endothelial cells, smooth muscle cells, and macrophages). Oxidized LDLs are enriched in oxidized products of cholesterol called oxysterols formed either by autoxidation, enzymatically, or by both mechanisms. Several oxysterols have been shown to accumulate in atheroma plaques and to play a key role in atherogenesis. Depending on the type of oxysterols, various biological effects are exerted on vascular cells to regulate the formation of macrophage foam cells, endothelial integrity, adhesion and transmigration of monocytes, plaque progression, and instability. Most of these effects are linked to the ability of oxysterols to induce cellular oxidative stress and cytotoxicity mainly through apoptosis and proinflammatory mediators. Like for excess cholesterol, high-density lipoproteins (HDL) can exert antiatherogenic activity by stimulating the efflux of oxysterols that have accumulated in foamy macrophages.
MeSH term(s)	Humans ; Oxysterols/metabolism ; Diabetes Mellitus, Type 2/complications ; Endothelial Cells/metabolism ; Lipoproteins, LDL/metabolism ; Atherosclerosis/metabolism ; Cholesterol/metabolism ; Plaque, Atherosclerotic
Chemical Substances	Oxysterols ; Lipoproteins, LDL ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2023-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	410187-X
ISSN	0065-2598
ISSN	0065-2598
DOI	10.1007/978-3-031-43883-7_11
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Article ; Online: Fatty Acid Composition and Metabolism in

Leroux, Marine / Luquain-Costaz, Céline / Lawton, Philippe / Azzouz-Maache, Samira / Delton, Isabelle

International journal of molecular sciences

2023 Volume 24, Issue 5

Abstract: Fatty acids have received growing interest ... ...

Abstract	Fatty acids have received growing interest in
MeSH term(s)	Animals ; Leishmania ; Fatty Acids ; Parasites ; Leishmaniasis ; Biomarkers
Chemical Substances	Fatty Acids ; Biomarkers
Language	English
Publishing date	2023-02-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24054702
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Article ; Online: Exosomal lipids from membrane organization to biomarkers: Focus on an endolysosomal-specific lipid.

Hullin-Matsuda, Françoise / Colosetti, Pascal / Rabia, Maxence / Luquain-Costaz, Céline / Delton, Isabelle

Biochimie

2022

Abstract: The term extracellular vesicles (EVs) has been recommended to describe various membrane-bound vesicles secreted by most living cells and found in various biological fluids. They gained growing interest as mediators of cell-cell communication and for ... ...

Abstract	The term extracellular vesicles (EVs) has been recommended to describe various membrane-bound vesicles secreted by most living cells and found in various biological fluids. They gained growing interest as mediators of cell-cell communication and for their roles in different patho-physiological processes. In addition, they were recently considered as disease biomarkers and new drug delivery systems. However, it is still difficult to link a biological function to a specific EV population among the heterogenous EV mixture secreted in the extracellular space due to limitations of optimal isolation methods. EV classification according to their size as small (<200 nm) and large (>200 nm) vesicles is also completed by the identification of selected proteins, nucleic acids and lipids. In this review, we summarized briefly knowledge about the composition and role of EV lipids that received less attention compared to their protein and nucleic acid content. Lipids are not only essential structural components of EVs, but can give important information on their biogenesis. Especially, we discussed our recent data showing the utility of bis(monoacylglycero)phosphate (BMP), a specific endolysosomal lipid marker, that could sign the endosomal origin of small EVs, classically named as exosomes.
Language	English
Publishing date	2022-09-30
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2022.09.016
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Article ; Online: Fatty Acid Composition and Metabolism in Leishmania Parasite Species

Marine Leroux / Céline Luquain-Costaz / Philippe Lawton / Samira Azzouz-Maache / Isabelle Delton

International Journal of Molecular Sciences, Vol 24, Iss 4702, p

Potential Biomarkers or Drug Targets for Leishmaniasis?

2023 Volume 4702

Abstract: Fatty acids have received growing interest in Leishmania biology with the characterization of the enzymes allowing the complete fatty acid synthesis of this trypanosomatid parasite. This review presents a comparative analysis of the fatty acid profiles ... ...

Abstract	Fatty acids have received growing interest in Leishmania biology with the characterization of the enzymes allowing the complete fatty acid synthesis of this trypanosomatid parasite. This review presents a comparative analysis of the fatty acid profiles of the major classes of lipids and phospholipids in different species of Leishmania with cutaneous or visceral tropism. Specificities relating to the parasite forms, resistance to antileishmanial drugs, and host/parasite interactions are described as well as comparisons with other trypanosomatids. Emphasis is placed on polyunsaturated fatty acids and their metabolic and functional specificities, in particular, their conversion into oxygenated metabolites that are inflammatory mediators able to modulate metacyclogenesis and parasite infectivity. The impact of lipid status on the development of leishmaniasis and the potential of fatty acids as therapeutic targets or candidates for nutritional interventions are discussed.
Keywords	fatty acids ; lipid mediators ; trypanosomatids ; leishmania ; leishmania/macrophage interactions ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses.

Luquain-Costaz, Céline / Rabia, Maxence / Hullin-Matsuda, Françoise / Delton, Isabelle

Biochimie

2020 Volume 179, Page(s) 247–256

Abstract: Viruses, including the novel coronavirus SARS-CoV-2, redirect infected cell metabolism to their own purposes. After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated ... ...

Abstract	Viruses, including the novel coronavirus SARS-CoV-2, redirect infected cell metabolism to their own purposes. After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated endocytosis ending in the acidic endolysosomal compartment. The virus hijacks the endosomal machinery leading to fusion of viral and endosomal membranes and release of the viral RNA into the cytosol. This mini-review specifically highlights the membrane lipid organization of the endosomal system focusing on the unconventional and late endosome/lysosome-specific phospholipid, bis(monoacylglycero)phosphate (BMP). BMP is enriched in alveolar macrophages of lung, one of the target tissue of SARS-CoV-2. This review details the BMP structure, its unsaturated fatty acid composition and fusogenic properties that are essential for the highly dynamic formation of the intraluminal vesicles inside the endosomes. Interestingly, BMP is necessary for infection and replication of enveloped RNA virus such as SARS-CoV-1 and Dengue virus. We also emphasize the role of BMP in lipid sorting and degradation, especially cholesterol transport in cooperation with Niemann Pick type C proteins (NPC 1 and 2) and with some oxysterol-binding protein (OSBP)-related proteins (ORPs) as well as in sphingolipid degradation. Interestingly, numerous virus infection required NPC1 as well as ORPs along the endocytic pathway. Furthermore, BMP content is increased during pathological endosomal lipid accumulation in various lysosomal storage disorders. This is particularly important knowing the high percentage of patients with metabolic disorders among the SARS-CoV-2 infected patients presenting severe forms of COVID-19.
MeSH term(s)	Cholesterol/metabolism ; Endocytosis ; Homeostasis ; Host Microbial Interactions ; Humans ; Lysophospholipids/metabolism ; Monoglycerides/metabolism ; SARS-CoV-2/physiology
Chemical Substances	Lysophospholipids ; Monoglycerides ; bis(monoacylglyceryl)phosphate ; Cholesterol (97C5T2UQ7J)
Keywords	covid19
Language	English
Publishing date	2020-11-05
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2020.10.018
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Article: Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses

Luquain-Costaz, Céline / Rabia, Maxence / Hullin-Matsuda, Françoise / Delton, Isabelle

Biochimie. 2020 Dec., v. 179

2020

Abstract	Viruses, including the novel coronavirus SARS-CoV-2, redirect infected cell metabolism to their own purposes. After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated endocytosis ending in the acidic endolysosomal compartment. The virus hijacks the endosomal machinery leading to fusion of viral and endosomal membranes and release of the viral RNA into the cytosol. This mini-review specifically highlights the membrane lipid organization of the endosomal system focusing on the unconventional and late endosome/lysosome-specific phospholipid, bis(monoacylglycero)phosphate (BMP). BMP is enriched in alveolar macrophages of lung, one of the target tissue of SARS-CoV-2. This review details the BMP structure, its unsaturated fatty acid composition and fusogenic properties that are essential for the highly dynamic formation of the intraluminal vesicles inside the endosomes. Interestingly, BMP is necessary for infection and replication of enveloped RNA virus such as SARS-CoV-1 and Dengue virus. We also emphasize the role of BMP in lipid sorting and degradation, especially cholesterol transport in cooperation with Niemann Pick type C proteins (NPC 1 and 2) and with some oxysterol-binding protein (OSBP)-related proteins (ORPs) as well as in sphingolipid degradation. Interestingly, numerous virus infection required NPC1 as well as ORPs along the endocytic pathway. Furthermore, BMP content is increased during pathological endosomal lipid accumulation in various lysosomal storage disorders. This is particularly important knowing the high percentage of patients with metabolic disorders among the SARS-CoV-2 infected patients presenting severe forms of COVID-19.
Keywords	COVID-19 infection ; Dengue virus ; RNA ; Severe acute respiratory syndrome coronavirus ; Severe acute respiratory syndrome coronavirus 2 ; cholesterol ; cytosol ; endocytosis ; endosomes ; fatty acid composition ; lungs ; macrophages ; metabolism ; peptidyl-dipeptidase A ; phosphates ; phospholipids ; sphingolipids ; unsaturated fatty acids ; viruses
Language	English
Dates of publication	2020-12
Size	p. 247-256.
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	120345-9
ISSN	0300-9084
ISSN	0300-9084
DOI	10.1016/j.biochi.2020.10.018
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses

Luquain-Costaz, Céline / Rabia, Maxence / Hullin-Matsuda, Françoise / Delton, Isabelle

Biochimie ; ISSN 0300-9084

2020

Keywords	Biochemistry ; General Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
DOI	10.1016/j.biochi.2020.10.018
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses

Luquain-Costaz, Céline / Rabia, Maxence / Hullin-Matsuda, Françoise / Delton, Isabelle

Biochimie

Abstract	Viruses, including the novel coronavirus SARS-CoV-2, redirect infected cell metabolism to their own purposes. After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated endocytosis ending in the acidic endolysosomal compartment. The virus hijacks the endosomal machinery leading to fusion of viral and endosomal membranes and release of the viral RNA into the cytosol. This mini-review specifically highlights the membrane lipid organization of the endosomal system focusing on the unconventional and late endosome/lysosome-specific phospholipid, bis(monoacylglycero)phosphate (BMP). BMP is enriched in alveolar macrophages of lung, one of the target tissue of SARS-CoV-2. This review details the BMP structure, its unsaturated fatty acid composition and fusogenic properties that are essential for the highly dynamic formation of the intraluminal vesicles inside the endosomes. Interestingly, BMP is necessary for infection and replication of enveloped RNA virus such as SARS-CoV-1 and Dengue virus. We also emphasize the role of BMP in lipid sorting and degradation, especially cholesterol transport in cooperation with Niemann Pick type C proteins (NPC 1 and 2) and with some oxysterol-binding protein (OSBP)-related proteins (ORPs) as well as in sphingolipid degradation. Interestingly, numerous virus infection required NPC1 as well as ORPs along the endocytic pathway. Furthermore, BMP content is increased during pathological endosomal lipid accumulation in various lysosomal storage disorders. This is particularly important knowing the high percentage of patients with metabolic disorders among the SARS-CoV-2 infected patients presenting severe forms of COVID-19.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #909113
Database	COVID19

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Article ; Online: Enriched PUFA environment of Leishmania infantum promastigotes promotes the accumulation of lipid mediators and favors parasite infectivity towards J774 murine macrophages.

Leroux, Marine / Bouazizi-Ben Messaoud, Hana / Luquain-Costaz, Céline / Jordheim, Lars P / Le Faouder, Pauline / Gustin, Marie-Paule / Aoun, Karim / Lawton, Philippe / Azzouz-Maache, Samira / Delton, Isabelle

Lipids

2022 Volume 58, Issue 2, Page(s) 81–92

Abstract: Leishmania parasites are the causative agents of visceral or cutaneous leishmaniasis in humans and of canine leishmaniosis. The macrophage is the predilected host cell of Leishmania in which the promastigote stage is transformed into amastigote. We ... ...

Abstract	Leishmania parasites are the causative agents of visceral or cutaneous leishmaniasis in humans and of canine leishmaniosis. The macrophage is the predilected host cell of Leishmania in which the promastigote stage is transformed into amastigote. We previously showed changes in the fatty acid composition (FA) of lipids in two strains of Leishmania donovani upon differentiation of promastigote to amastigote, including increased proportions of arachidonic acid (AA) and to a less extent of docosahexaenoic acid (DHA). Here, we carried out supplementation with AA or DHA on two Leishmania infantum strains, a visceral (MON-1) and a cutaneous (MON-24), to evaluate the role of these FA in parasite/macrophage interactions. The proportions of AA or DHA in total lipids were significantly increased in promastigotes cultured in AA- or DHA-supplemented media compared to controls. The content of FA-derived oxygenated metabolites was enhanced in supplemented strains, generating especially epoxyeicosatrienoic acids (11,12- and 14,15-EET) and hydroxyeicosatetraenoic acids (5- and 8- HETE) from AA, and hydroxydocosahexaenoic acids (14- and 17-HDoHE) from DHA. For both MON-1 and MON-24, AA-supplemented promastigotes showed higher infectivity towards J774 macrophages as evidenced by higher intracellular amastigote numbers. Higher infectivity was observed after DHA supplementation for MON-24 but not MON-1 strain. ROS production by macrophages increased upon parasite infection, but only minor change was observed between control and supplemented parasites. We propose that under high AA or DHA environment that is associated with AA or DHA enrichment of promastigote lipids, FA derivatives can accumulate in the parasite, thereby modulating parasite infectivity towards host macrophages.
MeSH term(s)	Humans ; Mice ; Animals ; Dogs ; Leishmania infantum/metabolism ; Parasites ; Macrophages/parasitology ; Leishmaniasis, Cutaneous/parasitology ; Arachidonic Acid/pharmacology ; Arachidonic Acid/metabolism ; Leishmaniasis, Visceral/parasitology ; Mice, Inbred BALB C
Chemical Substances	Arachidonic Acid (27YG812J1I)
Language	English
Publishing date	2022-12-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	241539-2
ISSN	1558-9307 ; 0024-4201
ISSN (online)	1558-9307
ISSN	0024-4201
DOI	10.1002/lipd.12365
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Article ; Online: Increased ABCA1 (ATP-Binding Cassette Transporter A1)-Specific Cholesterol Efflux Capacity in Schizophrenia.

Luquain-Costaz, Céline / Kockx, Maaike / Anastasius, Malcolm / Chow, Vincent / Kontush, Anatol / Jessup, Wendy / Kritharides, Leonard

Arteriosclerosis, thrombosis, and vascular biology

2020 Volume 40, Issue 11, Page(s) 2728–2737

Abstract: Objective: Patients with schizophrenia have increased long-term mortality attributable to cardiovascular disease and commonly demonstrate features of mixed dyslipidemia with low HDL-C (high-density lipoprotein cholesterol). The removal of cholesterol ... ...

Abstract	Objective: Patients with schizophrenia have increased long-term mortality attributable to cardiovascular disease and commonly demonstrate features of mixed dyslipidemia with low HDL-C (high-density lipoprotein cholesterol). The removal of cholesterol from cells by HDL via specific ATP-binding cholesterol transporters is a major functional property of HDL, and its measurement as cholesterol efflux capacity (CEC) can predict cardiovascular risk. Whether HDL function is impaired in patients with schizophrenia is unknown. Approach and Results: We measured basal and ABCA1 (ATP-binding cassette transporter A1)- and ABCG1 (ATP-binding cassette transporter G1)-dependent CEC, comparing patients with schizophrenia with age- and sex-matched healthy controls, and related our findings to nuclear magnetic resonance analysis of lipoprotein subclasses. Total plasma cholesterol and LDL-C (low-density lipoprotein cholesterol) were comparable between healthy controls (n=51) and patients (n=120), but patients with schizophrenia had increased total plasma triglyceride, low HDL-C and apo (apolipoprotein) A-I concentrations. Nuclear magnetic resonance analysis indicated a marked (15-fold) increase in large triglyceride-rich lipoprotein particle concentration, increased small dense LDL particles, and fewer large HDL particles. Despite lower HDL-C concentration, basal CEC was 13.7±1.6% higher, ABCA1-specific efflux was 35.9±1.6% higher, and ABCG1 efflux not different, in patients versus controls. In patients with schizophrenia, ABCA1-specific efflux correlated with the abundance of small 7.8 nm HDL particles but not with serum plasminogen or triglyceride levels. Conclusions: Patients with schizophrenia have increased concentrations of atherogenic apoB-containing lipoproteins, decreased concentrations of large HDL particles, but enhanced ABCA1-mediated CEC. In this population, preventative strategies should focus on reducing atherogenic lipoproteins rather than increasing CEC.
MeSH term(s)	ATP Binding Cassette Transporter 1/genetics ; ATP Binding Cassette Transporter 1/metabolism ; ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics ; ATP Binding Cassette Transporter, Subfamily G, Member 1/metabolism ; Adult ; Animals ; Antipsychotic Agents/therapeutic use ; Biomarkers/blood ; CHO Cells ; Case-Control Studies ; Cholesterol/blood ; Cricetulus ; Dyslipidemias/blood ; Dyslipidemias/diagnosis ; Female ; Humans ; Lipoproteins/blood ; Male ; Middle Aged ; Schizophrenia/blood ; Schizophrenia/diagnosis ; Schizophrenia/drug therapy ; Triglycerides/blood
Chemical Substances	ABCA1 protein, human ; ABCG1 protein, human ; ATP Binding Cassette Transporter 1 ; ATP Binding Cassette Transporter, Subfamily G, Member 1 ; Antipsychotic Agents ; Biomarkers ; Lipoproteins ; Triglycerides ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2020-09-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.120.314847
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