Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Netherlands Heart Institute, Utrecht, The Netherlands.
J Cardiovasc Transl Res. 2018 Feb;11(1):15-21. doi: 10.1007/s12265-017-9775-8. Epub 2017 Dec 28.
The interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) pathway is a potential pathophysiological mediator of cardiac fibrosis. Soluble ST2 (sST2) is one of the main isoforms of ST2 with strong prognostic value in cardiac disease. The exact role of sST2 in cardiac fibrosis is unknown. The aim of this study was (1) to investigate myocardial expression of the IL-33/ST2 pathway in relation to myocardial fibrosis in end-stage heart failure patients and (2) to study whether plasma sST2 is associated with histologically determined cardiac fibrosis. In 38 patients undergoing left ventricular assist device implantation, mRNA expression of sST2, total ST2, and IL-33 was measured in cardiac tissue obtained during the implantation. In the same tissue, histological fibrosis was digitally quantified and mRNA expression of pro-fibrotic signaling molecules, connective tissue growth factor (CTGF) and transforming growth factor beta 1 (TGFβ1), was measured. In addition, plasma levels of sST2 were determined. Expression levels of IL-33/ST2 pathway factors in myocardial tissue were significantly associated with cardiac fibrosis and the expression levels of CTGF and TGFβ1. Plasma levels of sST2 did not correlate with tissue expression of ST2, the amount of fibrosis or myocardial expression of pro-fibrotic signaling proteins. The interleukin-33/ST2 pathway is expressed in the failing human heart and its expression is associated with cardiac fibrosis and pro-fibrotic signaling proteins, suggesting a role in pro-fibrotic myocardial remodeling. Soluble ST2 levels in the circulation did not correlate with the amount of cardiac fibrosis or myocardial ST2 expression, however. Therefore, other pathophysiological processes such as inflammation might also substantially affect sST2 plasma levels.
白细胞介素-33（IL-33）/抑制肿瘤发生 2 型（ST2）途径是心脏纤维化的潜在病理生理介质。可溶性 ST2（sST2）是 ST2 的主要同工型之一，在心脏疾病中具有很强的预后价值。sST2 在心脏纤维化中的确切作用尚不清楚。本研究的目的是：（1）研究终末期心力衰竭患者心肌中 IL-33/ST2 途径的表达与心肌纤维化的关系；（2）研究血浆 sST2 是否与组织学确定的心脏纤维化相关。在 38 例行左心室辅助装置植入术的患者中，在植入过程中获取心脏组织，测量 sST2、总 ST2 和 IL-33 的 mRNA 表达。在相同的组织中，数字量化组织学纤维化，并测量促纤维化信号分子结缔组织生长因子（CTGF）和转化生长因子β1（TGFβ1）的 mRNA 表达。此外，还测定了血浆 sST2 水平。心肌组织中 IL-33/ST2 途径因子的表达水平与心脏纤维化以及 CTGF 和 TGFβ1 的表达水平显著相关。血浆 sST2 水平与组织中 ST2 的表达、纤维化的程度或心肌中促纤维化信号蛋白的表达均无相关性。IL-33/ST2 途径在衰竭的人心肌中表达，其表达与心脏纤维化和促纤维化信号蛋白相关，提示其在促纤维化的心肌重构中起作用。然而，循环中的可溶性 ST2 水平与心脏纤维化的程度或心肌 ST2 表达均无相关性。因此，其他病理生理过程，如炎症，也可能对 sST2 血浆水平产生重大影响。
