The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
J Cell Mol Med. 2018 Sep;22(9):4344-4353. doi: 10.1111/jcmm.13724. Epub 2018 Jul 4.
Atrial myocyte hypertrophy is one of the most important substrates in the development of atrial fibrillation (AF). The TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy in cardiomyopathy. This study therefore investigated the effects of Fn14 on atrial hypertrophy and underlying cellular mechanisms using HL-1 atrial myocytes. In patients with AF, Fn14 protein levels were higher in atrial myocytes from atrial appendages, and expression of TWEAK was increased in peripheral blood mononuclear cells, while TWEAK serum levels were decreased. In vitro, Fn14 expression was up-regulated in response to TWEAK treatment in HL-1 atrial myocytes. TWEAK increased the expression of ANP and Troponin T, and Fn14 knockdown counteracted the effect. Inhibition of JAK2, STAT3 by specific siRNA attenuated TWEAK-induced HL-1 atrial myocytes hypertrophy. In conclusion, TWEAK/Fn14 axis mediates HL-1 atrial myocytes hypertrophy partly through activation of the JAK2/STAT3 pathway.
心房肌细胞肥大是心房颤动（AF）发展的最重要底物之一。TWEAK/Fn14 轴是心肌病中心脏肥大的正调节剂。因此，本研究使用 HL-1 心房肌细胞研究了 Fn14 对心房肥大的影响及其潜在的细胞机制。在 AF 患者中，心房颤动附壁心肌细胞中的 Fn14 蛋白水平较高，外周血单个核细胞中 TWEAK 的表达增加，而 TWEAK 血清水平降低。在体外，TWEAK 处理可上调 HL-1 心房肌细胞中 Fn14 的表达。TWEAK 增加了 ANP 和肌钙蛋白 T 的表达，而 Fn14 敲低可拮抗该作用。特异性 siRNA 抑制 JAK2、STAT3 可减弱 TWEAK 诱导的 HL-1 心房肌细胞肥大。总之，TWEAK/Fn14 轴通过激活 JAK2/STAT3 通路介导 HL-1 心房肌细胞肥大。
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