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Heat shock proteins in stabilization of spontaneously restored sinus rhythm in permanent atrial fibrillation patients after mitral valve surgery

机译:热休克蛋白可稳定二尖瓣手术后永久性房颤患者自发恢复的窦性心律

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A spontaneously restored sinus rhythm in permanent atrial fibrillation patients has been often observed after mitral valve (MV) surgery, but persisting duration in sinus rhythm varies from patient to patient. Heat shock proteins (Hsps) may be involved in pathogenesis of atrial fibrillation. We hypothesized that stabilization of restored sinus rhythm is associated with expression of Hsps in the atria. To test this hypothesis, clinical data, biopsies of right atrial appendage, and blood samples were collected from 135 atrial fibrillation patients who spontaneously restored sinus rhythm after conventional isolated MV replacement. Comparison was made between patients who had recurrence of atrial fibrillation within 7?days (AF) vs. patients with persisted sinus rhythm for more than 7?days (SR). Results showed that SR patients had higher activity of heat shock transcription factor 1 (HSF1) as well as upregulated expressions of heat shock cognate 70, Hsp70, and Hsp27 in the tissues. The activation of HSF1–Hsps pathway was associated with less-aggressive pathogenesis as reflected by lower rates of myolysis, apoptosis, interstitial fibrosis, and inflammation in SR patients. However, Hsp60 was lower in both tissue and plasma in SR patients, and was positively correlated with apoptosis, interstitial fibrosis, and inflammation. These findings suggest that the Hsps play important roles in stabilization of restored sinus rhythm after MV surgery by inhibiting AF-related atrial remodeling and arrhythmogenic substrates in atrial fibrillation patients. Low circulating Hsp60 levels preoperatively might predict a stable spontaneously restored sinus rhythm postoperatively.
机译:在二尖瓣(MV)手术后,常观察到永久性房颤患者自发恢复窦性心律,但患者之间窦性心律的持续时间各不相同。热休克蛋白(Hsps)可能与房颤的发病机理有关。我们假设恢复窦性心律的稳定与心房中Hsps的表达有关。为了检验这一假设,从135例房颤患者中收集了常规分离的MV替代后自发恢复窦性心律的临床数据,右心耳活检和血样。比较了7天内(AF)发生房颤复发的患者和持续7天内(SR)持续窦性心律的患者。结果显示,SR患者具有较高的热休克转录因子1(HSF1)活性,并且组织中的热休克相关基因70,Hsp70和Hsp27的表达上调。 HSF1-Hsps途径的激活与侵略性发病机制相关,这表现为SR患者的肌溶解,细胞凋亡,间质纤维化和炎症发生率降低。然而,在SR患者中,Hsp60在组织和血浆中均较低,并且与细胞凋亡,间质纤维化和炎症呈正相关。这些发现表明,Hsps通过抑制房颤患者房颤相关的心房重构和心律失常底物,在稳定MV术后窦性心律中起着重要作用。术前低水平的Hsp60循环可能预示着术后自发恢复稳定的窦性心律。

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