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J Heart Lung Transplant. 2019 Sep;38(9):982-996. doi: 10.1016/j.healun.2019.06.010. Epub 2019 Jun 19.

ICAM-1 promotes the abnormal endothelial cell phenotype in chronic thromboembolic pulmonary hypertension.

Author information

1
Research and Innovation Unit; Department of Medicine, Stanford University, Stanford, California. Electronic address: jennifer.arthur.ataam@gmail.com.
2
Research and Innovation Unit; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation.
3
Research and Innovation Unit.
4
Research and Innovation Unit; Department of Medicine, Stanford University, Stanford, California.
5
Université de Montpellier, Montpellier, France.
6
Research and Innovation Unit; Department of Pathology, Marie Lannelongue Hospital, Le Plessis Robinson, France.
7
Department of Medicine, Stanford University, Stanford, California.

Abstract

BACKGROUND:

Pulmonary endothelial cells play a key role in the pathogenesis of Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Increased synthesis and/or the release of intercellular adhesion molecule-1 (ICAM-1) by pulmonary endothelial cells of patients with CTEPH has been recently reported, suggesting a potential role for ICAM-1 in CTEPH.

METHODS:

We studied pulmonary endarterectomy specimens from 172 patients with CTEPH and pulmonary artery specimens from 97 controls undergoing lobectomy for low-stage cancer without metastasis.

RESULTS:

ICAM-1 was overexpressed in vitro in isolated and cultured endothelial cells from endarterectomy specimens. Endothelial cell growth and apoptosis resistance were significantly higher in CTEPH specimens than in the controls (p < 0.001). Both abnormalities were abolished by pharmacological inhibition of ICAM-1 synthesis or activity. The overexpression of ICAM-1 contributed to the acquisition and maintenance of abnormal EC growth and apoptosis resistance via the phosphorylation of SRC, p38 and ERK1/2 and the overproduction of survivin. Regarding the ICAM-1 E469K polymorphism, the KE heterozygote genotype was significantly more frequent in CTEPH than in the controls, but it was not associated with disease severity among patients with CTEPH.

CONCLUSIONS:

ICAM-1 contributes to maintaining the abnormal endothelial cell phenotype in CTEPH.

KEYWORDS:

Adhesion molecules; Chronic thrombo-embolic hypertension; Endothelial dysfunction; ICAM-1; Survival signalling pathway

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