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001-es BibID:BIBFORM120915
035-os BibID:(Scopus)85125965764 (WoS)000743142600029
Első szerző:Akhmedov, Alexander
Cím:TNFα induces endothelial dysfunction in rheumatoid arthritis via LOX-1 and Arginase 2 : reversal by monoclonal TNFα antibodies / Alexander Akhmedov, Margot Crucet, Branko Simic, Simon Kraler, Nicole R. Bonetti, Caroline Ospelt, Oliver Distler, Adrian Ciurea, Luca Liberale, Matti Jauhiainen, Jari Metso, Melroy Miranda, Rose Cydecian, Lena Schwarz, Vera Fehr, Rita Zilinyi, Mohammad Amrollahi-Sharifabadi, Lydia Ntari, Niki Karagianni, Frank Ruschitzka, Reijo Laaksonen, Paul M. Vanhoutte, George Kollias, Giovanni G. Camici, Thomas F. Lüscher
Dátum:2022
ISSN:0008-6363
Megjegyzések:Aims: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting joints and blood vessels. Despite low levels of low-density lipoprotein cholesterol (LDL-C), RA patients exhibit endothelial dysfunction and are at increased risk of death from cardiovascular complications, but the molecular mechanism of action is unknown. We aimed in the present study to identify the molecular mechanism of endothelial dysfunction in a mouse model of RA and in patients with RA. Methods and results: Endothelium-dependent relaxations to acetylcholine were reduced in aortae of two tumour necrosis factor alpha (TNF?) transgenic mouse lines with either mild (Tg3647) or severe (Tg197) forms of RA in a time-and severity-dependent fashion as assessed by organ chamber myograph. In Tg197, TNF? plasma levels were associated with severe endothelial dysfunction. LOX-1 receptor was markedly up-regulated leading to increased vascular oxLDL uptake and NF?B-mediated enhanced Arg2 expression via direct binding to its promoter resulting in reduced NO bioavailability and vascular cGMP levels as shown by ELISA and chromatin immunoprecipitation. Anti-TNF? treatment with infliximab normalized endothelial function together with LOX-1 and Arg2 serum levels in mice. In RA patients, soluble LOX-1 serum levels were also markedly increased and closely related to serum levels of C-reactive protein. Similarly, ARG2 serum levels were increased. Similarly, anti-TNF? treatment restored LOX-1 and ARG2 serum levels in RA patients. Conclusions: Increased TNF? levels not only contribute to RA, but also to endothelial dysfunction by increasing vascular oxLDL content and activation of the LOX-1/NF?B/Arg2 pathway leading to reduced NO bioavailability and decreased cGMP levels. Anti-TNF? treatment improved both articular symptoms and endothelial function by reducing LOX-1, vascular oxLDL, and Arg2 levels. ? 2021 Published on behalf of the European Society of Cardiology. All rights reserved.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Arg2
Endothelium
LOX-1
Rheumatoid arthritis
TNFα
Megjelenés:Cardiovascular Research. - 118 : 1 (2022), p. 254-266. -
További szerzők:Crucet, Margot Simic, Branko Kraler, Simon Bonetti, Nicole R. Ospelt, Caroline Distler, Oliver Ciurea, Adrian Liberale, Luca Jauhiainen, Matti Metso, Jari Miranda, Melroy Cydecian, Rose Schwarz, Lena Fehr, Vera Zilinyi Rita (1990-) (Klinikai laboratóriumi kutató) Amrollahi-Sharifabadi, Mohammad Ntari, Lydia Karagianni, Niki Ruschitzka, Frank Laaksonen, Reijo Vanhoutte, Paul M. Kollias, George Camici, Giovanni G. Lüscher, Thomas F.
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