RESUMO
Accelerated senescence is triggered by key mediators of arrhythmogenic substrates and contributes to atrial fibrillation (AF). We sought to understand senescence in AF and the extent to which it aggravates the AF process. Twenty-six AF patients undergoing open-heart surgery were included, and 12 patients with sinus rhythm served as controls. Another cohort included 120 consecutive persistent AF patients with valvular heart diseases. HL-1 atrial myocytes were tachypaced (TP) to simulate experimental AF. Compared with sinus rhythm, left atrial appendages (LAAs) with AF presented a significantly increased positive area of cellular senescence, with upregulated expression of p16, p21 and p53. Next, p21 mRNA was increased in patients with AF recurrence compared with that in patients without recurrence. In multivariate analysis, p21 (OR: 2.97; 95% CI: 1.65-5.34; P<0.001) was a significant independent predictor of AF early recurrence. Interestingly, TP induced HL-1 atrial myocyte senescence in vitro, accompanied by a marked increase in the senescence-associated secretory phenotype (SASP) and altered the expression of sarcoplasmic reticulum (SR)-related proteins. Suppression of p21 by siRNA reduced TP induced cell senescence and IL-1ß, IL-6 elevation, and partly changed SR-related proteins expression. Moreover, we show that the level of γH2AX, a marker of DNA damage, was higher in AF patients than in sinus rhythm controls. Similarly, an increase in γH2AX levels was observed following TP. AF underlies cardiomyocyte senescence and contributes to deleterious atrial remodeling during disease progression. This finding may help facilitate the search for new therapeutic approaches for antiaging therapy for AF.
RESUMO
BACKGROUND: Monocyte-to-high-density lipoprotein (M/H) ratio has emerged as a novel cardiovascular prognostic biomarker. We aimed to evaluate the prognostic values of M/H with early recurrence in persistent valvular atrial fibrillation (AF) patients after radiofrequency (RF) maze procedure. METHODS: We retrospectively analyzed 131 consecutive persistent AF patients with valvular heart diseases who were followed up 3 months after RF maze procedure. Their clinical data were recorded. Logistic regression analyses were performed for significant predictors. Receiver operating characteristic analysis was used for validation with corresponding area under the curve. RESULTS: 70 (53.4%) patients experienced early recurrence after procedure. Patients with early recurrence were older, have longer AF duration history, larger left atria diameter (LAD), higher plasma C-reactive protein (CRP), lower triglycerides (TG), lower cholesterol (TC), increased monocyte counts, lower HDL cholesterol, and increased M/H ratio. In multivariate analysis, age (OR 1.1 95% CI 1.0-1.1 P = .003), LAD (OR 2.1, 95%CI 1.2-3.5, P = .006), TG (OR 0.35, 95% CI 0.15-0.84, P = .019), M/H (OR 6.1, 95% CI 2.9-13.0, P < .001) were significantly independent predictors of AF early recurrence. M/H ratio demonstrated a significant predictive value (AUC = 0.77, sensitivity 89.0%, specificity 54%). Further, there was a positive correlation of M/H ratio with CRP and white blood cell. CONCLUSION: Preoperative M/H ratio was an independent risk factor of AF early recurrence following RF maze operation. M/H ratio should be considered in prediction of early recurrence for valvular AF patients.
