SMAD3 and atrial fibrillation: In addition, intra-myocardial fibrosis, a hallmark of AF, was observed to increase in the atria of obese mice, as evidenced by aggravated collagen deposition, upregulated pro-fibrosis signaling (TGF-β, α-SMA, Smad3, collagen I, and collagen III), and downregulated transcription of anti-fibrotic Smad7 (Figures 2K–O).