Gardner George T, Travers Joshua G, Qian Jiang, Liu Guan-Sheng, Haghighi Kobra, Robbins Nathan, Jiang Min, Li Yutian, Fan Guo-Chang, Rubinstein Jack, Blaxall Burns C, Kranias Evangelia G
Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Department of Pediatrics, Division of Molecular Cardiovascular Biology, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
JACC Basic Transl Sci. 2019 Apr 29;4(2):188-199. doi: 10.1016/j.jacbts.2018.11.007. eCollection 2019 Apr.
Cardiomyocyte-specific increases in phosphorylated Hsp20 (S16D-Hsp20) to levels similar to those observed in human failing hearts are associated with early fibrotic remodeling and depressed left ventricular function, symptoms which progress to heart failure and early death. The underlying mechanisms appear to involve translocation of phosphorylated Hsp20 to the nucleus and upregulation of interleukin (IL)-6, which subsequently activates cardiac fibroblasts in a paracrine fashion through transcription factor STAT3 signaling. Accordingly, treatment of S16D-Hsp20 mice with a rat anti-mouse IL-6 receptor monoclonal antibody (MR16-1) attenuated interstitial fibrosis and preserved cardiac function. These findings suggest that phosphorylated Hsp20 may be a potential therapeutic target in heart failure.
心肌细胞中磷酸化Hsp20（S16D-Hsp20）特异性增加至与人类衰竭心脏中观察到的水平相似，这与早期纤维化重塑和左心室功能降低有关，这些症状会发展为心力衰竭和早期死亡。潜在机制似乎涉及磷酸化Hsp20易位至细胞核以及白细胞介素（IL）-6上调，随后通过转录因子STAT3信号以旁分泌方式激活心脏成纤维细胞。因此，用大鼠抗小鼠IL-6受体单克隆抗体（MR16-1）治疗S16D-Hsp20小鼠可减轻间质纤维化并保留心脏功能。这些发现表明磷酸化Hsp20可能是心力衰竭的一个潜在治疗靶点。
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