Comorbid TNF-mediated heart valve disease and chronic polyarthritis share common mesenchymal cell-mediated aetiopathogenesis

Annals of the Rheumatic Diseases
Lydia NtariGeorge Kollias

Abstract

Patients with rheumatoid arthritis and spondyloarthritisshow higher mortality rates, mainly caused by cardiac comorbidities. The TghuTNF (Tg197) arthritis model develops tumour necrosis factor (TNF)-driven and mesenchymalsynovial fibroblast (SF)-dependent polyarthritis. Here, we investigate whether this model develops, similarly to human patients, comorbid heart pathology and explore cellular and molecular mechanisms linking arthritis to cardiac comorbidities. Histopathological analysis and echocardiographic evaluation of cardiac function were performed in the Tg197 model. Valve interstitial cells (VICs) were targeted by mice carrying the ColVI-Cretransgene. Tg197 ColVI-Cre Tnfr1fl/fl and Tg197 ColVI-Cre Tnfr1cneo/cneo mutant mice were used to explore the role of mesenchymal TNF signalling in the development of heart valve disease. Pathogenic VICs and SFs were further analysed by comparative RNA-sequencing analysis. Tg197 mice develop left-sided heart valve disease, characterised by valvular fibrosis with minimal signs of inflammation. Thickened valve areas consist almost entirely of hyperproliferative ColVI-expressing mesenchymal VICs. Development of pathology results in valve stenosis and left ventricular dysfunction, accompa...Continue Reading

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Citations

Apr 5, 2018·Annals of the Rheumatic Diseases·Lars Vereecke, Dirk Elewaut
Jun 2, 2018·Annals of the Rheumatic Diseases·Pietro Enea LazzeriniPier Leopoldo Capecchi
Oct 1, 2019·Current Vascular Pharmacology·Iordanis S MourouzisConstantinos Pantos

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Methods Mentioned

BETA
transgenic
fluorescence-activated cell sorting
FACS

Software Mentioned

RNEA

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