Cardiac Dysfunction in Rheumatoid Arthritis: The Role of Inflammation

Figures

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  Figure 1. Cardiovascular disease in rheumatoid arthritis patients. Local and systemic inflammation may either directly affect the heart or make the heart more susceptible to traditional risk factors. Patients with rheumatoid arthritis (RA) have a higher susceptibility to ischemic and nonischemic heart disease. Both coronary artery disease and cardiac hypertrophy can result in heart failure.

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  Figure 2. The role of systemic inflammation in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFpEF). Inflammatory pathologies such as RA are associated with increased circulating levels of pro-inflammatory mediators. This results in endothelial activation and dysfunction and increased recruitment of leukocytes, such as monocytes into cardiac tissue. Increased oxidative stress contributes to a reduction in NO bioavailability and a subsequent reduction in cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG) in cardiac muscle leading to cardiac hypertrophy and increased resting tension. MHCII high macrophages produce osteopontin and TGF-β in response to autocrine stimulation by IL-10, which results in fibroblast proliferation and elevated collagen deposition. Ultimately, this results in increased stiffness and diastolic dysfunction.

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  Figure 3. Actions of current therapeutics and FPR2 agonists in the context of cardiovascular disease in rheumatoid arthritis patients. The mechanisms of action of current therapeutics in RA patients are indicated and colour coded in relation to their cardiovascular disease (CVD) risk with green being protective and red detrimental. Actions of pro-resolving mediators LXA4 (lipoxin A4), resolvin D1 (RvD1), annexin A1 (Anx-A1), and the synthetic agonist compound 17b (Cmpd17b) mediated through the G-protein coupled receptor FPR2 are also indicated. The lipid-lowering medications statins are also included, and their impact on C-reactive protein (CRP) is indicated, as is their role in the generation of 13-series resolvins (RvT) and 15-epi-LXA4.