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Pulmonary Production of Soluble ST2 in Heart Failure
Circulation: Heart Failure ( IF 9.7 ) Pub Date : 2018-12-13 , DOI: 10.1161/circheartfailure.118.005488
Domingo A. Pascual-Figal 1, 2, 3 , Maria T. Pérez-Martínez 1, 4 , Maria C. Asensio-Lopez 1 , Jesús Sanchez-Más 5 , Maria E. García-García 6 , Carlos M. Martinez 4 , Miriam Lencina 7 , Ruben Jara 6 , James L. Januzzi 8 , Antonio Lax 4
Affiliation  

Background:Serum concentrations of ST2 (interleukin-1 receptor-like 1) represent a meaningful prognostic marker in cardiac diseases. Production of soluble ST2 (sST2) may be partially extracardiac. Identification of sST2 sources is relevant to design strategies for modulating its signaling.Methods and Results:An experimental model of ischemic heart failure was used. sST2, membrane-bound ST2 (ST2L), and IL-33 were measured in lungs, heart, kidney, and liver by quantifying mRNA and protein expression in tissue samples obtained at different times (1, 2, 4, and 24 weeks). Primary human type II pneumocyte cell cultures were subjected to strain. sST2 was measured in samples of bronchial aspirate and serum obtained from patients treated with invasive respiratory support. In the experimental model, sST2 increased significantly from the first week in both lungs and myocardium, whereas ST2L/IL-33 response was unfavorable in lungs (decrease) and favorable in myocardium (increase). No changes were observed in liver and kidneys. ST2 immunostaining was intensely observed in alveolar epithelium, and sST2 was secreted by primary human type II pneumocytes in response to strain. sST2 levels in lung aspirates were substantially higher in the presence of cardiogenic pulmonary edema (median, 228 [interquartile range, 28.4–324.0] ng/mL; P<0.001) than bronchopneumonia (median, 5.5 [interquartile range, 1.6–6.5]) or neurological disorders (median, 2.9 [interquartile range, 1.7–10.1]), whereas sST2 concentrations in serum did not differ.Conclusions:The lungs are a relevant source of sST2 in heart failure. These results may have implications for the progression of disease and the development of therapies targeting the ST2 system in patients with heart failure.

中文翻译:

心力衰竭时肺中可溶性ST2的产生

背景:ST2(白介素-1受体样1)的血清浓度代表了心脏病中有意义的预后标志物。可溶性ST2(sST2)的产生可能是部分心外膜。sST2来源的识别与调节其信号转导的设计策略有关。方法和结果:使用了缺血性心力衰竭的实验模型。通过量化在不同时间(1、2、4和24周)获得的组织样本中的mRNA和蛋白质表达,在肺,心脏,肾脏和肝脏中测量了sST2,膜结合ST2(ST2L)和IL-33。对原代人II型肺细胞细胞培养物进行应变。在从有创呼吸支持治疗的患者中获得的支气管抽吸物和血清中测量了sST2。在实验模型中 从第一周开始,sST2在肺和心肌中均显着增加,而ST2L / IL-33反应在肺中不利(减少),而在心肌中有利(增加)。在肝和肾中未观察到变化。在肺泡上皮细胞中强烈观察到ST2免疫染色,并且响应于菌株,sST2由人类II型原发性肺细胞分泌。存在心源性肺水肿时,肺吸出物中的sST2水平明显更高(中位数为228 [四分位间距,28.4–324.0] ng / mL;P <0.001)高于支气管肺炎(中位数5.5 [四分位间距1.6-6.5])或神经系统疾病(中位数2.9 [四分位间距1.7-10.1]),而血清中sST2浓度无差异。心脏衰竭中sST2的相关来源。这些结果可能对心力衰竭患者的疾病进展和靶向ST2系统的疗法的发展有影响。
更新日期:2018-12-13
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