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| Pàgina inicial > Articles > Articles publicats > Malondialdehyde-modified HDL particles elicit a specific IgG response in abdominal aortic aneurysm |
(IIS-Fundación Jiménez-Díaz) (Odense University Hospital (Dinamarca)) (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares) (Institut d'Investigació Biomèdica Sant Pau) (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares) (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)| Data: | 2021 |
| Resum: | High Density Lipoprotein (HDL) plays a protective role in abdominal aortic aneurysm (AAA); however, recent findings suggest that oxidative modifications could lead to dysfunctional HDL in AAA. This study aimed at testing the effect of oxidized HDL on aortic lesions and humoral immune responses in a mouse model of AAA induced by elastase, and evaluating whether antibodies against modified HDL can be found in AAA patients. HDL particles were oxidized with malondialdehyde (HDL-MDA) and the changes were studied by biochemical and proteomics approaches. Experimental AAA was induced in mice by elastase perfusion and then mice were treated with HDL-MDA, HDL or vehicle for 14 days. Aortic lesions were studied by histomorphometric analysis. Levels of anti-HDL-MDA IgG antibodies were measured by an in-house immunoassay in the mouse model, in human tissue-supernatants and in plasma samples from the VIVA cohort. HDL oxidation with MDA was confirmed by enhanced susceptibility to diene formation. Proteomics demonstrated the presence of MDA adducts on Lysine residues of HDL proteins, mainly ApoA-I. MDA-modification of HDL abrogated the protective effect of HDL on cultured endothelial cells as well as on AAA dilation in mice. Exposure to HDL-MDA elicited an anti-HDL-MDA IgG response in mice. Anti-HDL-MDA were also detected in tissue-conditioned media from AAA patients, mainly in intraluminal thrombus. Higher plasma levels of anti-HDL-MDA IgG antibodies were found in AAA patients compared to controls. Anti-HDL-MDA levels were associated with smoking and were independent predictors of overall mortality in AAA patients. Overall, MDA-oxidized HDL trigger a specific humoral immune response in mice. Besides, antibodies against HDL-MDA can be detected in tissue and plasma of AAA patients, suggesting its potential use as surrogate stable biomarkers of oxidative stress in AAA. |
| Ajuts: | Ministerio de Asuntos Económicos y Transformación Digital SAF2016-80843-R Agencia Estatal de Investigación PID2019-106814RB-I00 Agencia Estatal de Investigación PGC2018-097019-B-I00 Instituto de Salud Carlos III PI19/00128 Instituto de Salud Carlos III Biobancos RD09/0076/00101 Instituto de Salud Carlos III PI16/00113 Instituto de Salud Carlos III PT17/0019/0003-ISCIII-SGEFI/ERDF |
| Nota: | Altres ajuts: Comunidad Autónoma de Madrid (Complemento II-CM, S2017/BMD-3673); Fondo Europeo de Desarrollo Regional (FEDER); Fundació "La Caixa" (HR17-00247). |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | HDL ; MDA ; Oxidative stress ; Immune response ; Antibodies ; Abdominal aortic aneurysm |
| Publicat a: | Free Radical Biology and Medicine, Vol. 174 (october 2021) , p. 171-181, ISSN 1873-4596 |
