Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/162704 |
Resumo: | 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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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:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:45:39Zoai:run.unl.pt:10362/162704Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:59:01.861962Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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