Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts

Bibliographic Details
Main Author: Lopes, Elizeth
Publication Date: 2023
Other Authors: Machado De Oliveira, Gisela, Guerreiro Simões, Catarina, Ferreira, Inês, Ramos, Cristiano Manuel Colaço, JS, Ramalho, Soares, Maria I. L., Melo, Teresa M. V. D. Pinho E, Puertollano, Rosa, R. A. Marques, André, Vieira, Larissa Abbud
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/162704
Summary: Funding Information: This work was financially supported by the FCT (Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Education), Refs. 2022.01305.PTDC and 2022.03249.PTDC. The Coimbra Chemistry Centre (CQC) is supported by the FCT through projects UIDB/00313/2020 and UIDP/00313/2020. E.L. is the holder of a PhD fellowship from the FCT (2021.06265.BD). A.R.A.M. was funded by the FCT Stimulus of Scientific Employment Individual Support Call 2017 (CEECIND/01006/2017). R.P. was funded by the NHLBI Division of Intramural Research (ZIA HL006151-10). Publisher Copyright: © 2023 by the authors.
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spelling Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblastsatherosclerosisautophagy and apoptosischolesteryl hemiazelatecholesteryl hemiesterslysosome dysfunctionmouse embryonic fibroblastsBiochemistry, Genetics and Molecular Biology(all)SDG 3 - Good Health and Well-beingFunding Information: This work was financially supported by the FCT (Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Education), Refs. 2022.01305.PTDC and 2022.03249.PTDC. The Coimbra Chemistry Centre (CQC) is supported by the FCT through projects UIDB/00313/2020 and UIDP/00313/2020. E.L. is the holder of a PhD fellowship from the FCT (2021.06265.BD). A.R.A.M. was funded by the FCT Stimulus of Scientific Employment Individual Support Call 2017 (CEECIND/01006/2017). R.P. was funded by the NHLBI Division of Intramural Research (ZIA HL006151-10). Publisher Copyright: © 2023 by the authors.There is growing evidence supporting the role of fibroblasts in all stages of atherosclerosis, from the initial phase to fibrous cap and plaque formation. In the arterial wall, as with macrophages and vascular smooth muscle cells, fibroblasts are exposed to a myriad of LDL lipids, including the lipid species formed during the oxidation of their polyunsaturated fatty acids of cholesteryl esters (PUFA-CEs). Recently, our group identified the final oxidation products of the PUFA-CEs, cholesteryl hemiesters (ChE), in tissues from cardiovascular disease patients. Cholesteryl hemiazelate (ChA), the most prevalent lipid of this family, is sufficient to impact lysosome function in macrophages and vascular smooth muscle cells, with consequences for their homeostasis. Here, we show that the lysosomal compartment of ChA-treated fibroblasts also becomes dysfunctional. Indeed, fibroblasts exposed to ChA exhibited a perinuclear accumulation of enlarged lysosomes full of neutral lipids. However, this outcome did not trigger de novo lysosome biogenesis, and only the lysosomal transcription factor E3 (TFE3) was slightly transcriptionally upregulated. As a consequence, autophagy was inhibited, probably via mTORC1 activation, culminating in fibroblasts’ apoptosis. Our findings suggest that the impairment of lysosome function and autophagy and the induction of apoptosis in fibroblasts may represent an additional mechanism by which ChA can contribute to the progression of atherosclerosis.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)iNOVA4Health - pólo NMSRUNLopes, ElizethMachado De Oliveira, GiselaGuerreiro Simões, CatarinaFerreira, InêsRamos, Cristiano Manuel ColaçoJS, RamalhoSoares, Maria I. L.Melo, Teresa M. V. D. Pinho EPuertollano, RosaR. A. Marques, AndréVieira, Larissa Abbud2024-01-24T16:59:44Z2023-122023-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/162704eng2073-4409PURE: 81977688https://doi.org/10.3390/cells12242826info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T18:17:41Zoai:run.unl.pt:10362/162704Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:48:11.044090Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts
title Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts
spellingShingle Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts
Lopes, Elizeth
atherosclerosis
autophagy and apoptosis
cholesteryl hemiazelate
cholesteryl hemiesters
lysosome dysfunction
mouse embryonic fibroblasts
Biochemistry, Genetics and Molecular Biology(all)
SDG 3 - Good Health and Well-being
title_short Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts
title_full Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts
title_fullStr Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts
title_full_unstemmed Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts
title_sort Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts
author Lopes, Elizeth
author_facet Lopes, Elizeth
Machado De Oliveira, Gisela
Guerreiro Simões, Catarina
Ferreira, Inês
Ramos, Cristiano Manuel Colaço
JS, Ramalho
Soares, Maria I. L.
Melo, Teresa M. V. D. Pinho E
Puertollano, Rosa
R. A. Marques, André
Vieira, Larissa Abbud
author_role author
author2 Machado De Oliveira, Gisela
Guerreiro Simões, Catarina
Ferreira, Inês
Ramos, Cristiano Manuel Colaço
JS, Ramalho
Soares, Maria I. L.
Melo, Teresa M. V. D. Pinho E
Puertollano, Rosa
R. A. Marques, André
Vieira, Larissa Abbud
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
iNOVA4Health - pólo NMS
RUN
dc.contributor.author.fl_str_mv Lopes, Elizeth
Machado De Oliveira, Gisela
Guerreiro Simões, Catarina
Ferreira, Inês
Ramos, Cristiano Manuel Colaço
JS, Ramalho
Soares, Maria I. L.
Melo, Teresa M. V. D. Pinho E
Puertollano, Rosa
R. A. Marques, André
Vieira, Larissa Abbud
dc.subject.por.fl_str_mv atherosclerosis
autophagy and apoptosis
cholesteryl hemiazelate
cholesteryl hemiesters
lysosome dysfunction
mouse embryonic fibroblasts
Biochemistry, Genetics and Molecular Biology(all)
SDG 3 - Good Health and Well-being
topic atherosclerosis
autophagy and apoptosis
cholesteryl hemiazelate
cholesteryl hemiesters
lysosome dysfunction
mouse embryonic fibroblasts
Biochemistry, Genetics and Molecular Biology(all)
SDG 3 - Good Health and Well-being
description Funding Information: This work was financially supported by the FCT (Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Education), Refs. 2022.01305.PTDC and 2022.03249.PTDC. The Coimbra Chemistry Centre (CQC) is supported by the FCT through projects UIDB/00313/2020 and UIDP/00313/2020. E.L. is the holder of a PhD fellowship from the FCT (2021.06265.BD). A.R.A.M. was funded by the FCT Stimulus of Scientific Employment Individual Support Call 2017 (CEECIND/01006/2017). R.P. was funded by the NHLBI Division of Intramural Research (ZIA HL006151-10). Publisher Copyright: © 2023 by the authors.
publishDate 2023
dc.date.none.fl_str_mv 2023-12
2023-12-01T00:00:00Z
2024-01-24T16:59:44Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/162704
url http://hdl.handle.net/10362/162704
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2073-4409
PURE: 81977688
https://doi.org/10.3390/cells12242826
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
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instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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