Authors
Jolyane Meloche, Aude Pflieger, Mylène Vaillancourt, Roxane Paulin, François Potus, Sotirios Zervopoulos, Colin Graydon, Audrey Courboulin, Sandra Breuils-Bonnet, Ève Tremblay, Christian Couture, Evangelos D Michelakis, Steeve Provencher, Sébastien Bonnet
Publication date
2014/2/18
Journal
Circulation
Volume
129
Issue
7
Pages
786-797
Publisher
Lippincott Williams & Wilkins
Description
Background
Pulmonary arterial hypertension (PAH) is associated with sustained inflammation known to promote DNA damage. Despite these unfavorable environmental conditions, PAH pulmonary arterial smooth muscle cells (PASMCs) exhibit, in contrast to healthy PASMCs, a pro-proliferative and anti-apoptotic phenotype, sustained in time by the activation of miR-204, nuclear factor of activated T cells, and hypoxia-inducible factor 1-α. We hypothesized that PAH-PASMCs have increased the activation of poly(ADP-ribose) polymerase-1 (PARP-1), a critical enzyme implicated in DNA repair, allowing proliferation despite the presence of DNA-damaging insults, eventually leading to PAH.
Methods and Results
Human PAH distal pulmonary arteries and cultured PAH-PASMCs exhibit increased DNA damage markers (53BP1 and γ-H2AX) and an overexpression of PARP-1 (immunoblot and activity assay), in …
Total citations
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Scholar articles
J Meloche, A Pflieger, M Vaillancourt, R Paulin, F Potus… - Circulation, 2014
J Meloche, A Pflieger, M Vaillancourt, R Paulin, F Potus… - Role for DNA damage signaling in pulmonary arterial …, 2014
A Courboulin, J Meloche, F Potus, G Margaillan… - A52. MECHANISMS OF PULMONARY VASCULAR …, 2013