Abstract： Objectives To determine the atrial expression of the collagen Ⅰ, collagen Ⅲ and the transforming growth factorbeta 1 (TGF-β1) in patients with rheumatic heart disease (RHD) and permanent atrial fibrillation(PAF) and to investigate the relationship between the extent of atrial fibrosis and the effectiveness of radiofrequency maze procedure in patients with RHD and PAF. Methods A total of 40 patients with RHD and PAF (≥6 months) who underwent a radiofrequency maze procedure with concomitant valvular surgery were collected for the experimental group. We acquired 100 mg of the left auricle tissue in each patient and followed up these patients after 3, 6 months of [CM(158mm]surgery. Then we assigned these patients to nonAF group and persistent AF group according to the results of the 6month followup. Another 10 patients with RHD and sinus rhythm(SR) who underwent valvular surgery alone were assigned to SR group and their left auricle tissue was also obtained. In order to determine the extent of atrial fibrosis, we observed the amount of collagen volume fraction Ⅰ，Ⅲ(CVF-Ⅰ,CVF-Ⅲ) by semiquantitative analysis with picrosirius red staining method. Using the β actin protein as the endogenous reference gene, we detected the expressions of TGF-β1 mRNA by semiquantitative reverse transcriptionpolymerase chain reaction(RT-PCR) technique. Results Each group has the same clinical baseline. At 6month follow-up, 28 among the 40 patients were categorized into the nonAF group and 12 into the AF group. (1) Patients in the nonAF group and the AF group had higher mRNA expressions of TGF-β1, CVF-Ⅰ and CVF-Ⅰ/CVF-Ⅲ compared with the SR group (F=6.487, P=0.003; F=3.711, P=0.032; F=3.697, P=0.032). The AF group had higher mRNA expressions of TGF-β1, CVF-Ⅰ and CVF-Ⅰ/CVF-Ⅲ than the nonAF group (t=4.372, P=0.043; t=4.603, P=0.038; t=4.776, P=0.035). But the CVFⅢ had no significant differences among the three groups (P＞0.05). (2) The patients whose left atrial function recovered after Maze procedure had lower mRNA expression than those patients whose left atrial function did not recover in the nonAF group (t=5.570, P=0.027). (3) The TGF-β1 mRNA expression has a positive correlation with both the contents of CVF-Ⅰ and left atrial diameter (r=0.786, Plt;0.05; r=0.858, Plt;0.05). Multiple logistic regression analysis revealed that the mRNA expression levels of TGF-β1, CVF-Ⅰ and left atrial diameter were independently associated with the postoperative persistence of atrial fibrillation. Conclusion The extent of atrial fibrosis in patients with RHD and PAF may be related to the sinus rhythm restoration and maintenance after AF surgical radiofrequency ablation and the resumption of atrial function.
This study was aimed to evaluate the relationship between the changes of plasma intermedin (IMD) and atrial fibrosis in hypertensive patients with atrial fibrillation. During the period from 2010 to 2011, appropriate 150 subjects of out-patients (female 50%,male 50%) were selected in West China Hospital, Sichuan University, and were divided into three groups: the hypertension-only group, the hypertension combined with paroxysmal atrial fibrillation group and the hypertension combined with persistent atrial fibrillation group. Firstly, we collected the Physical examination results and medical history records of the patients. We then performed ultrasound cardiogram and blood biochemical tests on the patients. We also detected the plasma IMD and transforming growth factor β1(TGF-β1) using ELISA. The results showed that compared with the hypertensive group, the plasma level of IMD, TGF-β1 and left atrium director (LAD) in the hypertensive combined with atrial fibrillation group were higher significantly. Compared with the paroxymal atrial fibrillation group, the levels of IMD, TGF-β1 and LAD were higher significantly in persistent atrial fibrillation group. Analysis of correlation and partial correlation showed that IMD was positively correlated with TGF-β1 (r=0.51, P<0.001), IMD was positively correlated with LAD(r=0.59, P<0.001), and TGF-β1 was positively correlated with LAD (r=0.57, P<0.001). The results suggest that IMD might suppress the pathophysiological process of atrial fibrillation.
ObjectiveTo explore the changes of focal adhesion kinase (FAK) in the fibrotic atrium of patients with valvular atrial fibrillation and explore its downstream signaling pathways.MethodsA total of 45 patients with mitral valve disease were included in this study and were divided into a valvular atrial fibrillation group (VAF, ≥6 months, 25 patients) and a sinus rhythm group (SR, 20 patients) based on having atrial fibrillation or not. The atrial appendage tissue was obtained during the operation , histopathological examination and Western blotting were performed. The degree of atrial fibrosis and changes in FAK and its downstream pathways in fibrotic myocardium were observed.ResultsThis study revealed a higher degree of atrial fibrosis in valvular atrial fibrillation and disordered cell arrangement. Expression of fibroblast differentiation marker alpha smooth muscle actin (α-SMA) was significantly increased in atrial fibrillation, and the expression of FAK and downstream AKT/S6K pathway proteins was up-regulated, while the other signal was observed, there was no significant change in ERK1/2 signaling pathway.ConclusionAtrial fibrosis in valvular atrial fibrillation is an important feature of atrial structural remodeling. We found overproduction of collagen fibers disrupted the continuity of atrial myocytes, leading to abnormal conduction and providing a matrix environment for the development of atrial fibrillation. The expression of focal adhesion kinase and downstream AKT/S6K signaling pathway in fibrotic myocardium may be involved in the process of atrial fibrosis, providing a basis for the study of its mechanism.