PUBLICATION
Cholesteryl hemiazelate Identified in Cardiovascular Disease Patients Causes in vitro and in vivo Inflammation
- Authors
- Domingues, N., Gaifem, J., Matthiesen, R., Saraiva, D.P., Bento, L., Marques, A.R.A., Soares, M.I.L., Sampaio, J., Klose, C., Surma, M.A., Almeida, M.S., Rodrigues, G., Gonçalves, P.A., Ferreira, J., E Melo, R.G., Pedro, L.M., Simons, K., Pinho E Melo, T.M.V.D., Cabral, M.G., Jacinto, A., Silvestre, R., Vaz, W., Vieira, O.V.
- ID
- ZDB-PUB-230724-39
- Date
- 2023
- Source
- Journal of Lipid Research 64(9): 100419 (Journal)
- Registered Authors
- Keywords
- Cholesteryl hemiazelate, Cholesteryl hemiesters, atherosclerosis, innate inflammatory responses, lipidomics
- MeSH Terms
-
- Animals
- Atherosclerosis*
- Cholesterol Esters
- Esters
- Humans
- Inflammation
- Monocytes
- Zebrafish*
- PubMed
- 37482218 Full text @ J. Lipid Res.
Citation
Domingues, N., Gaifem, J., Matthiesen, R., Saraiva, D.P., Bento, L., Marques, A.R.A., Soares, M.I.L., Sampaio, J., Klose, C., Surma, M.A., Almeida, M.S., Rodrigues, G., Gonçalves, P.A., Ferreira, J., E Melo, R.G., Pedro, L.M., Simons, K., Pinho E Melo, T.M.V.D., Cabral, M.G., Jacinto, A., Silvestre, R., Vaz, W., Vieira, O.V. (2023) Cholesteryl hemiazelate Identified in Cardiovascular Disease Patients Causes in vitro and in vivo Inflammation. Journal of Lipid Research. 64(9):100419.
Abstract
Oxidation of polyunsaturated fatty acids (PUFA) in low-density lipoproteins (LDL) 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 (ChE), 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 cardiovascular disease patients and identified four ChE types in human endarterectomy specimens. Cholesteryl hemiazelate (ChA), the cholesteryl hemiester of azelaic acid (n-nonane-1,9-dioic acid), was the most prevalent ChE identified in both cases. Importantly human monocytes, monocyte-derived macrophages (MDM) and neutrophils exhibit inflammatory features when exposed to sub-toxic concentrations of ChA in vitro. ChA increases the secretion of proinflammatory cytokines such as IL-1β and IL-6 and modulates the surface-marker profile of monocytes and MDM. 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 has pro-atherogenic properties and can be considered part of a damage-associated molecular pattern (DAMP) in the development of atherosclerosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping