We showed that expression of Ecrg4 is decreased in atrial appendages of AF patients and in atria of a canine AF model, and knockdown ECRG4 in atrial myocytes significantly increased the expression of pro-inflammatory cykotines (IL1a, IL6, MCP1), down-regulated Gap junction alpha-1 expression (Gja1), and up-regulated the expression of s100a1, s100a8, and MMP3. Here, S100A8 is linked to atrial fibrillation.