Myocardial pressure overload induces systemic inflammation through endothelial cell IL-33
Myocardial pressure overload induces systemic inflammation through endothelial cell IL-33
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DOI：
10.1073/pnas.1424236112
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发表时间：
2015-06-09
影响因子：
11.1
通讯作者：
Lee, Richard T.
中科院分区：
文献类型：
--
作者：
Chen, Wei-Yu;Hong, Jaewoo;Lee, Richard T.
高血压增加了心脏的压力负荷，并与慢性全身炎症状态知之甚少。白细胞介素33（IL-33）与膜结合的ST 2（ST 2L）结合，在心肌中具有抗肥大和抗纤维化作用。相比之下，可溶性ST 2似乎充当IL-33的诱饵受体，阻断心肌和血管益处，并且是心血管疾病患者的预后生物标志物。在这里，我们报告说，一个高度局部心肌内IL-33/ST 2的对话调节心脏的压力超负荷的反应。无论是内皮细胞特异性的IL 33缺失还是心肌细胞特异性的ST 2缺失都加剧了压力超负荷的心肌肥厚。此外，压力超负荷诱导全身循环IL-33以及全身循环IL-13和TGF-β 1;这被内皮细胞特异性缺失IL-33而不是心肌细胞特异性缺失IL-33所消除。我们的研究表明，内皮细胞分泌的IL-33是至关重要的翻译心肌压力超负荷到选择性全身炎症反应。
Hypertension increases the pressure load on the heart and is associated with a poorly understood chronic systemic inflammatory state. Interleukin 33 (IL-33) binds to membrane-bound ST2 (ST2L) and has antihypertrophic and antifibrotic effects in the myocardium. In contrast, soluble ST2 appears to act as a decoy receptor for IL-33, blocking myocardial and vascular benefits, and is a prognostic biomarker in patients with cardiovascular diseases. Here we report that a highly local intramyocardial IL-33/ST2 conversation regulates the heart's response to pressure overload. Either endothelial-specific deletion of IL33 or cardiomyocyte-specific deletion of ST2 exacerbated cardiac hypertrophy with pressure overload. Furthermore, pressure overload induced systemic circulating IL-33 as well as systemic circulating IL-13 and TGF-beta1; this was abolished by endothelial-specific deletion of IL33 but not by cardiomyocyte-specific deletion of IL33. Our study reveals that endothelial cell secretion of IL-33 is crucial for translating myocardial pressure overload into a selective systemic inflammatory response.