Atrial Fibrillation Progression Is Associated with Cell Senescence Burden as Determined by p53 and p16 Expression

Abstract

The expression of p53, p16, and tissue factor (TF) was significantly increased in AF compared to SR (0.91 ± 0.31 vs. 0.58 ± 0.31, <i>p</i> = 0.001; 0.76 ± 0.32 vs. 0.35 ± 0.18, <i>p</i> = 0.0001; 0.88 ± 0.32 vs. 0.68 ± 0.29, <i>p</i> = 0.045, respectively). Expression of endothelial NO synthase (eNOS) was lower in AF (0.25 ± 0.15 vs. 0.35 ± 0.12, <i>p</i> = 0.023). There was a stepwise increase of p53, p16, TF, matrix metalloproteinase-9, and an eNOS progressive decrease between SR, PAF, and PmAF. AF was the only predictive factor of p53 and p16 elevation in multivariate analysis. <i>Conclusions:</i> The study brought new evidence indicating that AF progression is strongly related to human atrial senescence burden and points at a link between senescence, thrombogenicity, endothelial dysfunction and atrial remodeling.