Reconciling paradigms of abnormal pulmonary blood flow and quasi-malignant cellular alterations in pulmonary arterial hypertension

Vascular Pharmacology
C M HappéHarm J Bogaard

Abstract

In pulmonary arterial hypertension (PAH) structural and functional abnormalities of the small lung vessels interact and lead to a progressive increase in pulmonary vascular resistance and right heart failure. A current pathobiological concept characterizes PAH as a 'quasi-malignant' disease focusing on cancer-like alterations in endothelial cells (EC) and the importance of their acquired apoptosis-resistant, hyper-proliferative phenotype in the process of vascular remodeling. While changes in pulmonary blood flow (PBF) have been long-since recognized and linked to the development of PAH, little is known about a possible relationship between an altered PBF and the quasi-malignant cell phenotype in the pulmonary vascular wall. This review summarizes recognized and hypothetical effects of an abnormal PBF on the pulmonary vascular bed and links these to quasi-malignant changes found in the pulmonary endothelium. Here we describe that abnormal PBF does not only trigger a pulmonary vascular cell growth program, but may also maintain the cancer-like phenotype of the endothelium. Consequently, normalization of PBF and EC response to abnormal PBF may represent a treatment strategy in patients with established PAH.

Associated Clinical Trials

Aug 16, 2017·Steeve Provencher

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Jan 24, 2018·EuroIntervention : Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology·Kazuya HosokawaHiroyuki Tsutsui
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