The hallmarks of severe pulmonary arterial hypertension: The cancer hypothesis-Ten years later

Carlyne D. Cool, Wolfgang M. Kuebler, Harm Jan Bogaard, Edda Spiekerkoetter, Mark R. Nicolls, Norbert F. Voelkel*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review


Severe forms of pulmonary arterial hypertension (PAH) are most frequently the consequence of a lumen-obliterating angiopathy. One pathobiological model is that the initial pulmonary vascular endothelial cell injury and apoptosis is followed by the evolution of phenotypically altered, apoptosis-resistant, proliferating cells and an inflammatory vascular immune response. Although there may be a vasoconstrictive disease component, the increased pulmonary vascular shear stress in established PAH is caused largely by the vascular wall pathology. In this review, we revisit the “quasi-malignancy concept” of severe PAH and examine to what extent the hallmarks of PAH can be compared with the hallmarks of cancer. The cancer model of severe PAH, based on the growth of abnormal vascular and bone marrow-derived cells, may enable the emergence of novel cell-based PAH treatment strategies.

Original languageEnglish
Pages (from-to)L1115-L1130
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number6
Publication statusPublished - Jun 2020

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