TGF-β is a potent stimulator of collagen production by cardiac fibroblasts, and elevated serum TGF-β levels in patients with AF, as well as increased levels of both TGF-β itself and downstream Smad4 with prolonged duration of AF, allow myocardial fibroblasts to proliferate and promote collagen synthesis, which in turn exerts a pro-fibrotic effect on the atria (Schwarte-Waldhoff and Schmiegel, 2002; Li et al., 2008; Gramley et al., 2010). Here, SMAD4 is linked to atrial fibrillation.