Authors:	Marczynski, Paul Meineck, Myriam Xia, Ning Li, Huige Kraus, Daniel Roth, Wilfried Möckel, Tamara Boedecker, Simone Schwarting, Andreas Weinmann-Menke, Julia
Title:	Vascular inflammation and dysfunction in lupus-prone mice-IL-6 as mediator of disease initiation
Online publication date:	31-May-2021
Year of first publication:	2021
Language:	english
Abstract:	Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable to lupus-specific risk factors (i.e., increased systemic inflammation, altered immune status), apart from traditional CV risk factors. To date, there is no established experimental model to explore the pathogenesis of this increased CV risk in SLE patients. Methods: Here we investigated whether MRL-Faslpr mice, which develop an SLE-like phenotype, may serve as a model to study lupus-mediated vascular disease. Therefore, MRL-Faslpr, MRL-++, and previously generated Il6−/− MRL-Faslpr mice were used to evaluate vascular changes and possible mechanisms of vascular dysfunction and damage. Results: Contrary to MRL-++ control mice, lupus-prone MRL-Faslpr mice exhibited a pronounced vascular and perivascular leukocytic infiltration in various organs; expression of pro-inflammatory cytokines in the aorta and kidney was augmented; and intima-media thickness of the aorta was increased. IL-6 deficiency reversed these changes and restored aortic relaxation. Conclusion: Our findings demonstrate that the MRL-Faslpr mouse model is an excellent tool to investigate vascular damage in SLE mice. Moreover, IL-6 promotes vascular inflammation and damage and could potentially be a therapeutic target for the treatment of accelerated arteriosclerosis in SLE.
DDC:	570 Biowissenschaften 570 Life sciences 610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-5927
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	International journal of molecular sciences 22 5
Pages or article number:	2291
Publisher:	Molecular Diversity Preservation International
Publisher place:	Basel
Issue date:	2021
ISSN:	1422-0067 1661-6596
Publisher URL:	https://doi.org/10.3390/ijms22052291
Publisher DOI:	10.3390/ijms22052291
Appears in collections:	JGU-Publikationen