Coronary microembolization (CME) has a poor prognosis, with ventricular arrhythmia being the most serious consequence. Understanding the underlying mechanisms could improve its management. We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on connexin-43 (Cx43) expression and ventricular arrhythmia susceptibility after CME. Forty male rabbits were randomized into four groups (n = 10 each): Sham, CME, G-CSF, and AG490 (a JAK2 selective inhibitor). Rabbits in the CME, G-CSF, and AG490 groups underwent left anterior descending (LAD) artery catheterization and CME. Animals in the G-CSF and AG490 groups received intraperitoneal injection of G-CSF and G-CSF + AG490, respectively. The ventricular structure was assessed by echocardiography. Ventricular electrical properties were analyzed using cardiac electrophysiology. The myocardial interstitial collagen content and morphologic characteristics were evaluated using Masson and hematoxylin-eosin staining, respectively. Western blot and immunohistochemistry were employed to analyze the expressions of Cx43, G-CSF receptor (G-CSFR), JAK2, and STAT3. The ventricular effective refractory period (VERP), VERP dispersion, and inducibility and lethality of ventricular tachycardia/fibrillation were lower in the G-CSF than in the CME group (P < 0.01), indicating less severe myocardial damage and arrhythmias. The G-CSF group showed higher phosphorylated-Cx43 expression (P < 0.01 vs. CME). Those G-CSF-induced changes were reversed by A490, indicating the involvement of JAK2. G-CSFR, phosphorylated-JAK2, and phosphorylated-STAT3 protein levels were higher in the G-CSF group than in the AG490 (P < 0.01) and Sham (P < 0.05) groups. G-CSF might attenuate myocardial remodeling via JAK2-STAT3 signaling and thereby reduce ventricular arrhythmia susceptibility after CME.

中文翻译：

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在兔冠状动脉微栓塞模型中，粒细胞集落刺激因子通过JAK2-STAT3途径减弱心肌重塑和室性心律不齐的敏感性。

冠状动脉微栓塞（CME）的预后较差，以室性心律不齐为最严重的后果。了解基本机制可以改善其管理。我们调查了粒细胞集落刺激因子（G-CSF）对CME后连接蛋白43（Cx43）表达和室性心​​律失常敏感性的影响。40只雄性兔被随机分为四组（每组n = 10）：假手术，CME，G-CSF和AG490（一种JAK2选择性抑制剂）。在CME，G-CSF和AG490组中的兔子接受了左前降（LAD）动脉导管和CME。G-CSF和AG490组的动物分别接受腹膜内注射G-CSF和G-CSF + AG490。通过超声心动图评估心室结构。使用心脏电生理分析心室电特性。分别使用Masson和苏木精-伊红染色评估心肌间质胶原含量和形态特征。免疫印迹和免疫组化分析了Cx43，G-CSF受体（G-CSFR），JAK2和STAT3的表达。与CME组相比，G-CSF的心室有效不应期（VERP），VERP分散度，室速/纤颤的诱导性和致死性均较CME组低（P <0.01），表明严重的心肌损害和心律不齐。G-CSF组显示更高的磷酸化Cx43表达（相对于CME，P <0.01）。那些由G-CSF诱导的变化被A490逆转，表明JAK2参与其中。G-CSF组的G-CSFR，磷酸化JAK2和磷酸化STAT3蛋白水平高于AG490（P <0.01）和Sham（P < 0.05）组。G-CSF可能通过JAK2-STAT3信号传导减弱心肌重塑，从而降低CME后的室性心律失常敏感性。