Role of inflammation in atrial fibrillation pathophysiology and management

Abstract

Atrial fibrillation (AF) is the most common clinically relevant arrhythmia, but the methods available for treating AF and its complications (of which the most important is thrombogenesis), as well as for assessing AF risk and underlying pathophysiology, are largely limited. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF. That evidence includes elevated serum levels of inflammatory biomarkers in AF subjects, the expression of inflammatory markers in cardiac tissues of AF patients and animal models of AF, and beneficial effects of anti-inflammatory drugs in experimental AF paradigms. Inflammation is suggested to be linked to various pathological processes, such as oxidative stress, apoptosis, and fibrosis, that promote AF substrate formation. Inflammation has also been associated with endothelial dysfunction, platelet activation, and coagulation cascade activation, leading to thrombogenesis. Thus, inflammation may contribute to both the occurrence/maintenance of AF and its thromboembolic complications. Here, we review the evidence for a role of inflammation and inflammatory biomarkers in the risk management and treatment of AF. We also summarize the current knowledge of inflammation-dependent cellular and molecular mechanisms in AF pathophysiology and their potential as therapeutic targets.

Figure 1

Potential factors linking atrial fibrillation (AF) with inflammation. CAD, coronary artery disease; HF, heart failure; HT, hypertension.

Figure 2

Inflammation-related cellular and molecular pathophysiology in atrial fibrillation (AF) progression. ECM, extracellular matrix; IL-6, interleukin-6; MAPK, mitogen-activated protein kinase; NFAT, nuclear factor of activated T-cells; NF-κB, nuclear factor κ-light-chain-enhancer of activated B-cells; PKC, protein kinase C; RAAS, renin-angiotensin-aldosterone system; ROS, reactive oxygen species; Smad2/3, SMA- and MAD-related proteins, TGF-β, transforming growth factor-β; TNF-α, tissue necrosis factor-α.

Figure 3

Potential mechanisms underlying thrombogenesis in atrial fibrillation (AF) and the role of inflammation. TF, tissue factor; vWF, von Willebrand factor.