Promoter methylation induced by hypoxia results in a 50% decrease in PLK2 expression in atrial fibrillation (AF) patients; In canine tachycardia, PLK2 expression is decreased in tissues of atria, but not ventricles; Drug inhibition or KO of PLK2 leads to cardiac fibroblasts displaying myofibroblast phenotype; PLK2 KO mouse heart fibroblasts secretes inflammatory OPN; The concentration of OPN in peripheral blood of AF patients with myocardial fibrosis is significantly higher than that of patients with sinus rhythm and AF patients without fibrosis. This evidence concerns the gene SPP1 and Myocardial fibrosis.