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.
Highlights
Atrial fibrillation (AF) has become a serious epidemic across the world, and the incidence is expected to double within the 20 years [1,2,3]
Left atrial diameter (LAD) was significantly increased in the AF groups compared to sinus rhythm (SR) group, and it was larger in persistent AF (PeAF) group than in paroxysmal AF (PaAF) group
We evaluated the expression of senescence markers, SA-β-gal, P21CIP1/WAF1 and P16INK4a in left atrial appendages (LAAs), and tried to explore the association of senescence and fibrosis
Summary
Atrial fibrillation (AF) has become a serious epidemic across the world, and the incidence is expected to double within the 20 years [1,2,3]. There is considerable progression in the diagnosis and treatment of AF, it is associated with increased morbidity and mortality [2]. It is generally known that atrial fibrosis contributes to atrial structural remodeling, leading to the development and maintenance of AF [4, 5]. Short telomere length is a hallmark of aging and is associated with the incidence of AF [6], indicating it as a major risk factor for AFs. Replicative senescence appears to be a fundamental role in aging , which is characterized by DNA damage and telomere erosion, contributing to cardiomyocyte hypertrophy, increased apoptosis, decreased myocyte number and myocardial fibrosis [7, 8]. Whereas premature senescence is an irreversible form of cell-cycle arrest and primarily designed to initiate the elimination of damaged cells [7]. P16 and P21 were up-regulated in senescent cells and senescenceassociated β-galactosidase (SA-β-gal) distinguishes them from quiescent cells [9]
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