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肺动脉内膜切除术标本中的内皮细胞具有很高的血管生成潜能，并表达高水平的肝细胞生长因子。

Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor.

机构信息

Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba City, 260-8670, Japan.

Department of Advancing Research on Treatment Strategies for respiratory disease, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-Ku, Chiba City, 260-8670, Japan.

出版信息

BMC Pulm Med. 2018 Dec 29;18(1):197. doi: 10.1186/s12890-018-0769-3.

DOI:10.1186/s12890-018-0769-3
PMID:30594174
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6310963/
Abstract

BACKGROUND

Impaired angiogenesis is assumed to be an important factor in the development of chronic thromboembolic pulmonary hypertension (CTEPH). However, the role of endothelial cells (ECs) in CTEPH remains unclear. The aim of this study was to investigate the angiogenic potential of ECs from pulmonary endarterectomy (PEA) specimens.

METHODS

We isolated ECs from PEA specimens (CTEPH-ECs) and control EC lines from the intact pulmonary arteries of patients with peripheral lung cancers, using a MACS system. These cells were analyzed in vitro including PCR-array analysis, and the PEA specimens were analyzed with immunohistochemistry. Additionally, the serum HGF levels were determined in CTEPH patients.

RESULTS

A three-dimensional culture assay revealed that CTEPH-ECs were highly angiogenic. An angiogenesis-focused gene PCR array revealed a high expression of hepatocyte growth factor (HGF) in CTEPH-ECs. The high expression of HGF was also confirmed in the supernatant extracted from PEA specimens. The immunohistochemical analysis showed expression of HGF on the surface of the thrombus vessels. The serum HGF levels in CTEPH patients were higher than those in pulmonary thromboembolism survivors.

CONCLUSION

Our study suggests that there are ECs with pro-angiogenetic character and high expression of HGF in PEA specimens. It remains unknown how these results are attributable to the etiology. However, further investigation focused on the HGF pathway may provide novel diagnostic and therapeutic tools for patients with CTEPH.

摘要

背景

血管生成受损被认为是慢性血栓栓塞性肺动脉高压（CTEPH）发展的一个重要因素。然而，内皮细胞（ECs）在 CTEPH 中的作用仍不清楚。本研究旨在探讨肺动脉内膜切除术（PEA）标本中 ECs 的血管生成潜能。

方法

我们使用 MACS 系统从 PEA 标本（CTEPH-ECs）和周围型肺癌患者完整肺动​​脉的对照 EC 系中分离 ECs。在体外对这些细胞进行分析，包括 PCR 芯片分析，并对 PEA 标本进行免疫组化分析。此外，还测定了 CTEPH 患者的血清 HGF 水平。

结果

三维培养试验表明，CTEPH-ECs 具有高度的血管生成能力。血管生成焦点基因 PCR 芯片显示 CTEPH-ECs 中肝细胞生长因子（HGF）表达水平较高。从 PEA 标本中提取的上清液也证实了 HGF 的高表达。免疫组化分析显示血栓血管表面表达 HGF。CTEPH 患者的血清 HGF 水平高于肺血栓栓塞幸存者。

结论

我们的研究表明，PEA 标本中存在具有促血管生成特性和高表达 HGF 的 ECs。这些结果与病因的关系尚不清楚。然而，进一步集中研究 HGF 通路可能为 CTEPH 患者提供新的诊断和治疗工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/d0aaf26bd53e/12890_2018_769_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/40af8cdc442c/12890_2018_769_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/e5bc0cf47ad1/12890_2018_769_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/b215800ce1ed/12890_2018_769_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/60143134807c/12890_2018_769_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/b455d8b0fc52/12890_2018_769_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/d0aaf26bd53e/12890_2018_769_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/40af8cdc442c/12890_2018_769_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/be6c0a16ce83/12890_2018_769_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/e5bc0cf47ad1/12890_2018_769_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/ac83cc5e2abe/12890_2018_769_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/b215800ce1ed/12890_2018_769_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/60143134807c/12890_2018_769_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/b455d8b0fc52/12890_2018_769_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1647/6310963/d0aaf26bd53e/12890_2018_769_Fig8_HTML.jpg

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