| Objective:The AngⅡ/Rac1/STAT3(AngiotensinⅡ/rac GTPase activatingprotein1/signal transducers and activators of transcription3) is a important signalingpathway in the atrial myocardium to mediate atrial structural remodeling andmaintenance of atrial fibrillation. But atrial structural remodeling development in withpermanent atrial fibrillation patients with left atrial enlargement. We discuss the inpermanent atrial fibrillation patients with rheumatic heart disease, with left atrialenlargement increased the AngⅡ/Rac1/STAT3signaling pathway express levelalteration.Method:1. Ten rheumatic heart disease patients with sinus rhythm (SR) as control group(Agroup), and twenty rheumatic heart disease patients with permanent atrial fibrillation(AF) as research group. The research group according to left atrial dimension (LAD)divide for two groups, LAD50-65mm of B group, LAD＞65mm of C group, eachgroup of ten patients.2. The tissues were obtained from the right atrial appendage during the open-heartcardiac surgery for studies. During the open-heart cardiac surgery, the right atrialappendage was cannulated for extracorporeal circulation. The tissue from the tip of rightatrial appendage was collected when the appendage was sutured after the surgery. Allmyocardial specimens were quickly frozen in liquid nitrogen.3. For each sample, histological examination was performed with routinehematoxylin/eosin and Masson’s trichrome staining. Stained light microscopic picturesof atrial tissues from patients in each group, and analysis myocardial fibrosis degree. AngⅡ concentration was measured by enzyme-linked immunosorbent assay (ELISA)in atrial tissues. Changes in the protein expression of Rac1and STAT3were thendetermined by Western blot in atrial tissues from patients.4. SPSS17.0was used for statistical analysis. Continuous variables are reported asmean±SD. Continuous data from＞2groups were compared with1-way ANOVA.The relationships between the results data and left atrial dimension were evaluated byPearson’s coefficient of correlation analysis. Statistical significance was established at P＜0.05.Results:1. In permanent atrial fibrillation patients with rheumatic heart disease with leftatrial enlargement development showed more fibrosis within the intercellular space thanthe control group.2. AngⅡ levels in atrial tissues and found significantly higher levels of tissuesAngⅡ in permanent atrial fibrillation patients compared with controls. In atrial tissuesAngⅡ concentration(ng/mg protein)，C group levels of AngⅡwere significantlyincreased in both as compared with that of A and B group (4.59±2.565vs0.93±0.326,p＜0.001;4.59±2.565vs1.61±0.409, p＜0.001, respectively). No significant in levelsof AngⅡ between B group and A group (1.61±0.409vs0.93±0.326, p=0.321), but Bgroup the levels of AngⅡ was increased. Therefore，in atrial tissues AngⅡ levelssignificantly increased with left atrial enlargement development and positivelycorrelated with LAD(r=0.845, p＜0.001).3. Western blotting: The protein levels of Rac1expression in atrial tissues, nosignificant in B group compared with A group and C group compared with B group(0.373±0.175vs0.229±0.088, p=0.112;0.535±0.275vs0.373±0.175, p=0.074,respectively), but protein levels of Rac1expression were increased. In C group proteinlevels of Rac1expression was significantly increased compared with Agroup(0.535±0.275vs0.229±0.088, p＜0.01). Thus protein levels of Rac1expression inatrial tissues increased with left atrial enlargement development and positivelycorrelated with LAD(r=0.737, p＜0.001).4. Western blotting: The protein levels of STAT3expression in atrial tissues,significantly increased in both as in B group and C group compared with Agroup(0.773±0.376vs0.436±0.099, p＜0.05;0.990±0.469vs0.436±0.099, p＜0.01,respectively). No significant in C group compared with B group(0.990±0.469vs0.773±0.376, p=0.179), but protein levels of STAT3expression was increased. Accordingly, protein levels of STAT3expression in atrial tissues increased with leftatrial enlargement development and positively correlated with LAD(r=0.575, p＜0.001).Conclusions:1. The AngⅡ/Rac1/STAT3is a important signaling pathway in the atrialmyocardium to mediate atrial structural remodeling and maintenance of permanentatrial fibrillation.2. In permanent atrial fibrillation patients with rheumatic heart disease with leftatrial enlargement development showed more fibrosis than the sinus rhythm group.Meanwhile, atrial myocardial fibrosis degree positively correlated with LAD.3. In permanent atrial fibrillation patients with rheumatic heart disease，the levelsof AngⅡ/Rac1/STAT3signaling pathway expression in atrial tissues significantlyincreased with left atrial enlargement development. |
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