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

Abstract

BackgroundImpaired 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.MethodsWe 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.ResultsA 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.ConclusionOur 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.Electronic supplementary materialThe online version of this article (10.1186/s12890-018-0769-3) contains supplementary material, which is available to authorized users.

Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension

“…In this study, we showed that CTEPH-EC also grew at a consistently faster rate and presented higher number of Ki-67 + cells when compared to healthy endothelial cells. This result is in line with previous publications in which they also showed greater proliferation capacity of CTEPH-EC denoting the involvement of endothelial cells in pulmonary artery occluding lesions 10,20 . In this study, we additionally demonstrated that CTEPH-EC had a significantly higher clonogenic potential and could survive for many more cell culture passages without losing their proliferative potential and phenotype.…”

Derivation and Characterisation of Endothelial Cells from Patients with Chronic Thromboembolic Pulmonary Hypertension.

“…In this study, we showed that CTEPH-EC also grew at a consistently faster rate and presented higher number of Ki-67 + cells when compared to healthy endothelial cells. This result is in line with a recent publication by Naito et al in which they showed greater proliferative potential of CTEPH-EC [17]. In this study, we additionally demonstrated that CTEPH-EC had a signi cantly higher clonogenic potential and could survive for many more cell culture passages without losing their proliferative potential and phenotype.…”

Endothelial Dysfunction in Pulmonary Hypertension: Cause or Consequence?

“…The existence of endothelial dysfunction in CTEPH pathogenesis is further supported by the fact that conditioned medium from CTEPH-derived PAECs, containing high levels of growth factors and inflammatory cytokines, increased PASMC proliferation and monocyte migration [ 157 ]. In addition, PAECs from CTEPH patients show an increased proliferation, altered angiogenic potential and metabolism, and apoptosis resistance [ 158 , 159 , 160 , 161 , 162 ]. Increased levels of soluble intracellular adhesion molecule-1 (ICAM1) in PAECs from CTEPH patients and in endarterectomy may contribute to EC proliferation and apoptosis resistance through its effect on cell survival pathways [ 161 ].…”