• Cardiovascular Disease
• Tnf-alpha
• Rheumatoid Arthritis
• Spondyloarthritis

Increasing evidence points to cardiovascular comorbidities in patients with rheumatic diseases, particularly in rheumatoid arthritis (RA) and spondyloarthritis (SpA).1 Ischaemic heart disease, valvular involvement including insufficiency and stenosis and arrhythmias can be observed as typical manifestations. They are a major cause of increased morbidity and mortality. While the epidemiological evidence is overwhelming, the underlying mechanisms why chronic inflammatory diseases affect the cardiovascular system are only partially understood. Treatment with anti-tumour necrosis factor (TNF) biologics ameliorates the risk for these comorbidities.1 However, insights into the underlying mechanisms and information on responsible cell-type linking arthritis and cardiac disease are yet unclear.

In this issue, Ntari et al describe spontaneous cardiac pathology in a preclinical model of arthritis driven by chronic human TNF expression. They show that TNF signalling in mesenchymal cells is both necessary and sufficient for the development of heart valve pathology in the presented mouse model.2

Human TNF transgenic mice which develop spontaneous arthritis (Tg197 line)3 were backcrossed to colVI-Cre TNFR1^fl/fl versus TNFR1^cneo/cneo mutant mice. This approach permits selective mesenchymal-specific genetic ablation versus reactivation of TNF/TNF-receptor 1 (TNFR1), including valve interstitial cells (VICs) of the heart. The same group previously showed that TNF signalling in mesenchymal cells is sufficient to drive chronic gut and joint pathology in an alternative TNF-overexpressing mouse model.4 In humans, synovial fibroblasts in the joints and intestinal mesenchymal cells in the gut regulate pathological mechanisms during arthritis5 and inflammatory bowel disease (IBD),6 which indicates …