Cholesteryl hemiazelate identified in CVD patients causes in vitro and in vivo inflammation

• Autor(a) principal: Domingues, Neuza
• Data de Publicação: 2023
• Outros Autores: Gaifem, Joana, Matthiesen, Rune, Saraiva, Diana P., Bento, Luís, Marques, André R.A., Soares, Maria I.L., Sampaio, Julio, Klose, Christian, Surma, Michal A., Almeida, Manuel S., Rodrigues, Gustavo, Gonçalves, Pedro Araújo, Ferreira, Jorge, Melo, Ryan Gouveiae, Pedro, Luís Mendes, Simons, Kai, Pinho e Melo, Teresa M.V.D., Guadalupe Cabral, M., Jacinto, Antonio, Silvestre, Ricardo, Vaz, Winchil, Vieira, Otília V.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/158604
• topic: atherosclerosis; cholesteryl hemiazelates; cholesteryl hemiesters; innate inflammatory responses; lipidomics; Biochemistry; Endocrinology; Cell Biology; SDG 3 - Good Health and Well-being

Funding Information: supported by FCT through projects UIDB/00313/2020 and UIDP/00313/2020. Funding Information: R. S. group has been funded by national funds, through the FCT—project numbers UIDB/50026/2020 and UIDP/ 50026/2020 and 2020.00185. CEECIND to the FCT. Funding Information: N. D. was a holder of a PhD fellowship from the FCT (Ref. N◦: SFRH/BD/51877/2012). Funding Information: The authors acknowledge the technical support of the Microscopy and Fish Facilities NOVA Medical School. They also acknowledge the UC-NMR facility for obtaining the NMR data (http://www.nmrccc.uc.pt). This work was also supported by the Biobanco-iMM, Lisbon Academic Medical Center, Lisbon, Portugal. This work was financially supported by the Foundation for Science and Technology (FCT) of the Portuguese Ministry of Science and Higher Education through national funds, project reference: 2022.01305.PTDC. The Coimbra Chemistry Centre is Fig. 7. Working model of the proatherogenic properties of ChA. ChA is an end product of cholesteryl linoleate oxidation, generated in the arterial intima. Because of its amphiphilic properties, ChA can be detected in the plasma of CVD patients. The presence of ChA in circulation can imprint an inflammatory phenotype in the circulating monocytes and neutrophils (1), conditioning the immunological response in the arterial intima. ChA promotes the recruitment of innate immune cells, neutrophils, and monocytes into the vasculature (2). Here, neutrophils in the presence of ChA secret IL-1β, which can interfere with monocyte/ macrophage priming. Monocytes differentiated in the presence of ChA are activated, increasing the secretion of inflammatory cytokines: IL-1β, IL-6, and IL-10 (3). In activated macrophages, ChA induces lipid accumulation (foam cells) and lysosomal dysfunction, conferring then the second signal necessary for IL-1β secretion mediated by inflammasome activation (4). IL-1β can initiate a propagation loop of the inflammation, increasing the macrophage secretion of IL-6 and TNF-α. On the other hand, dysfunctional lysosomes will decrease the clearance capacity of macrophages, leading to lipid accumulation in the arterial intima. Publisher Copyright: © 2023 THE AUTHORS.