IL-1β and TNF-α upregulate angiotensin II type 1 (AT1) receptors on cardiac fibroblasts and are associated with increased AT1 density in the post-MI heart
IL-1β and TNF-α upregulate angiotensin II type 1 (AT1) receptors on cardiac fibroblasts and are associated with increased AT1 density in the post-MI heart
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DOI：
10.1016/j.yjmcc.2004.12.015
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发表时间：
2005-03-01
影响因子：
5
通讯作者：
Greenberg, BH
中科院分区：
文献类型：
--
作者：
Gurantz, D;Cowling, RT;Greenberg, BH
血管紧张素（Ang） II在心肌梗死后（MI）心脏重构中起重要作用。介导大多数Ang II效应的I型受体AT(1)在心肌梗死后的非肌细胞中表达上调。我们已经证明，促炎细胞因子通过nf - κ B激活的机制增加心脏成纤维细胞上AT(1)受体的密度。本研究考察了新生大鼠心脏成纤维细胞中肿瘤坏死因子- α (tnf - α)和白细胞介素-1 β (IL-1 β)诱导的AT(1)受体上调的体外动力学，并评估了这些药物的出现与心肌梗死后AT(1)受体密度增加之间的时空关联。结果表明，IL-1 β比tnf - α更快地诱导AT(1)受体上调，这种效应可以被nf - κ b依赖性荧光素酶报告基因模拟。此外，这些促炎细胞因子的作用是叠加的。通过对心肌梗死后大鼠心脏的免疫组织化学研究，我们发现成纤维细胞和巨噬细胞梗死周围（PI）区tnf - α、IL-1 β和AT(1)受体蛋白之间存在很强的时空相关性。心肌梗死后1至7天，PI区细胞因子和AT(1)受体的标记强度随着替代疤痕的形成而增加。心肌梗死后，这种标记在疤痕周围的非肌细胞中持续了83天。这些发现表明，IL-1 β和tnf - α协同作用，增加心肌梗死后心脏非肌细胞上AT(1)受体的密度，这种作用可能有助于细胞外基质重塑和纤维化。(c) 2005年Elsevier Ltd出版
Angiotensin (Ang) II plays an important role in post-myocardial infarction (MI) cardiac remodeling. The Ang II type I (AT(1)) receptor which mediates most Ang II effects is upregulated on non-myocytes in the post-MI heart. We have shown that pro-inflammatory cytokines increase AT(1) receptor density on cardiac fibroblasts through a mechanism involving NF-kappa B activation. This study examines the in vitro kinetics of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) induced AT(1) receptor upregulation in neonatal rat cardiac fibroblasts and assesses temporal and spatial associations between the appearance of these agents and increased AT(1) receptor density post-MI. The results show that IL-1 beta more rapidly induces AT(1) receptor upregulation than does TNF-alpha, an effect that can be mimicked by a NF-kappa B-dependent luciferase reporter gene. Moreover, the effects of these pro-inflammatory cytokines are additive. Using immunohistochemistry in the post-MI rat heart we found strong temporal and spatial correlations between TNF-alpha, IL-1 beta and AT(1) receptor proteins in the peri-infarction (PI) zone in fibroblasts and macrophages. Labeling intensity for the cytokines and the AT(1) receptor increased from 1 to 7 days post-MI in the PI zone in conjunction with replacement scar formation. This labeling persisted in non-myocytes bordering the scar for up to 83 days post-MI. These findings suggest that IL-1 beta and TNF-alpha act coordinately to increase AT(1) receptor density on non-myocytes in the post-MI heart and that this effect may contribute to extracellular matrix remodeling and fibrosis. (c) 2005 Published by Elsevier Ltd.