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

Autor:	Domingues N; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, (NMS, FCM), Universidade Nova de Lisboa, Lisboa, Portugal., Gaifem J; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Portugal and ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal., Matthiesen R; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, (NMS, FCM), Universidade Nova de Lisboa, Lisboa, Portugal., Saraiva DP; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, (NMS, FCM), Universidade Nova de Lisboa, Lisboa, Portugal., Bento L; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, (NMS, FCM), Universidade Nova de Lisboa, Lisboa, Portugal., Marques ARA; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, (NMS, FCM), Universidade Nova de Lisboa, Lisboa, Portugal., Soares MIL; Department of Chemistry, Coimbra Chemistry Centre, Institute of Molecular Sciences, University of Coimbra, Coimbra, Portugal., Sampaio J; Lipotype GmbH, Dresden, Germany., Klose C; Lipotype GmbH, Dresden, Germany., Surma MA; Lipotype GmbH, Dresden, Germany., Almeida MS; Hospital Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Carnaxide, Portugal., Rodrigues G; Hospital Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Carnaxide, Portugal., Gonçalves PA; Hospital Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Carnaxide, Portugal., Ferreira J; Hospital Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Carnaxide, Portugal., E Melo RG; Department of Vascular Surgery, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte (CHULN), Lisboa, Portugal., Pedro LM; Department of Vascular Surgery, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte (CHULN), Lisboa, Portugal., Simons K; Lipotype GmbH, Dresden, Germany., Pinho E Melo TMVD; Department of Chemistry, Coimbra Chemistry Centre, Institute of Molecular Sciences, University of Coimbra, Coimbra, Portugal., Cabral MG; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, (NMS, FCM), Universidade Nova de Lisboa, Lisboa, Portugal., Jacinto A; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, (NMS, FCM), Universidade Nova de Lisboa, Lisboa, Portugal., Silvestre R; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Portugal and ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal., Vaz W; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, (NMS, FCM), Universidade Nova de Lisboa, Lisboa, Portugal., Vieira OV; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, (NMS, FCM), Universidade Nova de Lisboa, Lisboa, Portugal. Electronic address: otilia.vieira@nms.unl.pt.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2023 Sep; Vol. 64 (9), pp. 100419. Date of Electronic Publication: 2023 Jul 21.
DOI:	10.1016/j.jlr.2023.100419
Abstrakt:	Oxidation of PUFAs in LDLs trapped in the arterial intima plays a critical role in atherosclerosis. Though there have been many studies on the atherogenicity of oxidized derivatives of PUFA-esters of cholesterol, the effects of cholesteryl hemiesters (ChEs), the oxidation end products of these esters, have not been studied. Through lipidomics analyses, we identified and quantified two ChE types in the plasma of CVD patients and identified four ChE types in human endarterectomy specimens. Cholesteryl hemiazelate (ChA), the ChE of azelaic acid (n-nonane-1,9-dioic acid), was the most prevalent ChE identified in both cases. Importantly, human monocytes, monocyte-derived macrophages, and neutrophils exhibit inflammatory features when exposed to subtoxic concentrations of ChA in vitro. ChA increases the secretion of proinflammatory cytokines such as interleukin-1β and interleukin-6 and modulates the surface-marker profile of monocytes and monocyte-derived macrophage. In vivo, when zebrafish larvae were fed with a ChA-enriched diet, they exhibited neutrophil and macrophage accumulation in the vasculature in a caspase 1- and cathepsin B-dependent manner. ChA also triggered lipid accumulation at the bifurcation sites of the vasculature of the zebrafish larvae and negatively impacted their life expectancy. We conclude that ChA behaves as an endogenous damage-associated molecular pattern with inflammatory and proatherogenic properties. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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