Cardiac phenotype in mouse models of systemic autoimmunity

Abstract

Patients suffering from systemic autoimmune diseases are at significant risk of cardiovascular complications. This can be due to systemically increased levels of inflammation leading to accelerated atherosclerosis, or due to direct damage to the tissues and cells of the heart. Cardiac complications include an increased risk of myocardial infarction, myocarditis and dilated cardiomyopathy, valve disease, endothelial dysfunction, excessive fibrosis, and bona fide autoimmune-mediated tissue damage by autoantibodies or auto-reactive cells. There is, however, still a considerable need to better understand how to diagnose and treat cardiac complications in autoimmune patients. A range of inducible and spontaneous mouse models of systemic autoimmune diseases is available for mechanistic and therapeutic studies. For this Review, we systematically collated information on the cardiac phenotype in the most common inducible, spontaneous and engineered mouse models of systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis. We also highlight selected lesser-known models of interest to provide researchers with a decision framework to choose the most suitable model for their study of heart involvement in systemic autoimmunity.

Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles

“…The association of CuO NPs inhalation with cancer is further supported by the fact that pathways in cancer were deregulated after 3 days and 2 weeks of exposure. The deregulation of dilated cardiomyopathy pathway is most likely linked to changes in the immune response in the exposed mice [41]. The induction of olfactory transduction pathway after 2 weeks and 3 months of treatment is unexpected, considering the fact that non-olfactory tissues were investigated.…”

Layer‐specific strain and dyssynchrony index alteration in new-onset systemic lupus erythematosus patients without cardiac symptom

“…Mouse model and clinical evidence had shown lupus-associated risk factors play key roles in pathogenesis of CVD in SLE patients (20,21). Disease activity, in ammation, antiphospholipid antibody and lupus nephritis are among the most commonly studied SLE-associated cardiovascular risk factors (22,23,24).…”

Chronic inflammatory diseases, myocardial function and cardioprotection

“…These findings point out that 6-mercaptopurine might accelerate the evolution of atherosclerosis and CVD (Prüfer et al, 2014). With respect to anti-TNF-α agents, a slight non-significant decrease of ischaemic heart disease is observed in users when compared to non-users in an inflammatory bowel disease patient's cohort study (Rungoe et al, 2013). More recently, anti-TNF-α agents, infliximab and adalimumab, Danish cohort of patients with inflammatory bowel disease (Rungoe et al, 2013).…”

“…With respect to anti-TNF-α agents, a slight non-significant decrease of ischaemic heart disease is observed in users when compared to non-users in an inflammatory bowel disease patient's cohort study (Rungoe et al, 2013). More recently, anti-TNF-α agents, infliximab and adalimumab, Danish cohort of patients with inflammatory bowel disease (Rungoe et al, 2013). On the other hand, another study could not demonstrate differences in vascular parameters (carotid intima-media thickness, carotid plaque, and aortic stiffness) among patients treated with steroids (Cappello et al, 2017).…”

“…Decreased risk of IHD in IBD patients (Rungoe et al, 2013) 6-Mercaptopurine Induction of calcium deposition in in vitro cultured vascular smooth muscle cells and in ex vivo media layer of rat aorta rings which might accelerate the evolution of arteriosclerosis and CVD (Prüfer et al, 2014) Anti-TNF-α Non-significant decrease of IHD in IBD patients (Rungoe et al, 2013) Azathioprine + aminosalicylates Lower risk of CVD (calculated by Framingham Risk Score, a gender-specific algorithm for estimating the 10-year CV risk) in comparison to aminosalicilates only, and increased anti-inflammatory cytokines in women with ulcerative colitis (UC; dos Santos et al, 2015) Abbreviations: AMI, acute myocardial infarction; AMPK, AMP-activated protein kinase; ApoE, apolipoprotein E; CREB, cAMP response element-binding protein; CHF, congestive heart failure; CV, cardiovascular; Fra2, fos-related antigen-2; GF, growth factor; IHD, ischaemic heart disease; PTP-PEST, tyrosine-protein phosphatase non-receptor type 12; RTK, receptor tyrosine-kinases.…”