Endothelial-Derived Endothelin-1 Promotes Pulmonary Vascular Remodeling in Bleomycin-Induced Pulmonary Fibrosis
Endothelial-Derived Endothelin-1 Promotes Pulmonary Vascular Remodeling in Bleomycin-Induced Pulmonary Fibrosis
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DOI：
10.33549/physiolres.933812
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发表时间：
2018-01-01
影响因子：
2.1
通讯作者：
Emoto, N.
中科院分区：
文献类型：
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作者：
Hartopo, A. B.;Arfian, N.;Emoto, N.
内皮素-1（ET-1）可诱导肺血管重构和继发于肺纤维化的肺动脉高压。鉴于内皮细胞是ET-1的主要来源，并且来自其他细胞的ET-1可能难以穿透血管隔室，我们假设内皮源性ET-1促进继发于肺纤维化的血管重塑。我们使用血管内皮ET-1基因敲除（VEETKO）和野生型小鼠进行这项研究。它们被腹膜内给予博来霉素并在第28天被安乐死。定量肺纤维化程度，检测肺组织ET-1及其受体表达，计算中膜指数、肌化指数、外膜胶原、外膜成纤维细胞和巨噬细胞聚集，评价肺血管重构。还评估了右心室重构。VEETKO和野生型小鼠都发生了相当的肺纤维化和相似的纤维化相关基因表达。与野生型小鼠相比，博莱霉素诱导的VEETKO小鼠具有较低的ET-1肽水平（15.4 pg/mg vs. 31.2 pg/mg，p
Endothelin-1 (ET-1) induces pulmonary vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. Given that endothelial cells are the main source of ET-1 and ET-1 from other cells may encounter difficulty penetrating vascular compartments, we hypothesize that endothelial-derived ET-1 promotes vascular remodeling secondary to pulmonary fibrosis. We used vascular endothelial ET-1 knock-out (VEETKO) and Wild type mice for this research. They were given intratracheal bleomycin and euthanized at day 28. We quantified pulmonary fibrosis, measured lung ET-1 and its receptors' expression, and assessed pulmonary vascular remodeling by calculating medial wall index, muscularization index, adventitial collagen and adventitial fibroblast and macrophage accumulation. Right ventricle remodeling was also assessed. Both VEETKO and Wild type mice developed comparable pulmonary fibrosis and similar fibrosis-related gene expression. Compared to Wild type mice, bleomycin-induced VEETKO mice had lower ET-1 peptide levels (15.4 pg/mg vs. 31.2 pg/mg, p