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

• DOI: 10.1016/j.jlr.2023.100419
• Publication Date: 2023-07-22T00:59:58Z
• Authors: Neuza Domingues; Joana Gaifem; Rune Matthiesen; Diana P. Saraiva; Luís Bento; André R.A. Marques; Maria I.L. Soares; Julio Sampaio; Christian Klose; Michal A. Surma; Manuel S. Almeida; Gustavo Rodrigues; Pedro Araújo Gonç...; Jorge Ferreira; Ryan Gouveia e Melo; Luís Mendes Pedro; Kai Simons; Teresa M.V.D. Pin...; M. Guadalupe Cabral; Antonio Jacinto; Ricardo Silvestre; Winchil Vaz; Otília V. Vieira
• Keywords: Proinflammatory cytokine; Cholesteryl ester

Oxidation of PUFAs in LDLs trapped the arterial intima plays a critical role atherosclerosis. Though there have been many studies on atherogenicity oxidized derivatives PUFA-esters cholesterol, effects cholesteryl hemiesters (ChEs), oxidation end products these esters, not studied. Through lipidomics analyses, we identified and quantified two ChE types plasma CVD patients four human endarterectomy specimens. Cholesteryl hemiazelate (ChA), azelaic acid (n-nonane-1,9-dioic acid), was most prevalent both cases. Importantly, monocytes, monocyte-derived macrophages, neutrophils exhibit inflammatory features when exposed to subtoxic concentrations ChA vitro. increases secretion proinflammatory cytokines such as interleukin-1β interleukin-6 modulates surface-marker profile monocytes macrophage. In vivo, zebrafish larvae were fed with ChA-enriched diet, they exhibited neutrophil macrophage accumulation vasculature caspase 1- cathepsin B-dependent manner. also triggered lipid at bifurcation sites negatively impacted their life expectancy. We conclude that behaves an endogenous damage-associated molecular pattern proatherogenic properties.