Premature senescence of cardiac fibroblasts and atrial fibrosis in patients with atrial fibrillation

Abstract

Premature senescence is associated with atrial fibrosis and has an antifibrotic effect in mice. However, the role of senescence in atrial fibrillation (AF) remains unclear. Here, we investigated the association of premature senescence with fibrosis and also determined the role of senescence in the recurrence of AF after surgery ablation. Western blot, Sirius red staining, SA-β-gal staining and immunohistochemistry were performed to detect the degree of atrial fibrosis ,the expression of TGF-β and collagens, and also the senescence markers in 72 tissue specimens of left atrial appendage in this study. Then the patients undergoing successful surgical ablation were followed up for 12 months. The expression of collagens and TGF-β was paralleled by a high level of atrial fibrosis and were increased in AF group, especially in the persistent AF group. Western blotting of P16 and SA-β-gal staining showed an increased premature senescence in the sinus rhythm, paroxysmal AF and persistent AF groups. In addition, positive area of senescence markers, SA-β-gal and P16, was correlated positively with fibrotic lesions. We also found a lower ratio of P16/TGF-β in patients with recurrence of AF than in patients without recurrent AF. In conclusion, premature senescence is associated with atrial fibrosis in AF, and may have an antifibrotic role in AF.