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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Aged
  • Cells, Cultured
  • Chronic Disease
  • Endothelial Cells / metabolism
  • Female
  • Humans
  • Hypertension, Pulmonary / etiology*
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Intercellular Adhesion Molecule-1 / physiology*
  • Male
  • Middle Aged
  • Phenotype
  • Pulmonary Embolism / etiology*


  • ICAM1 protein, human
  • Intercellular Adhesion Molecule-1