title: DNA Damage and Pulmonary Hypertension.
abstract: Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis.
authors.affiliation: Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Qu&#233;bec, Universit&#233; Laval, Qu&#233;bec City, QC G1V 4G5, Canada. benoit.ranchoux@gmail.com.
authors.forename: Benoît
authors.initials: B
authors.lastname: Ranchoux
authors.affiliation: Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Qu&#233;bec, Universit&#233; Laval, Qu&#233;bec City, QC G1V 4G5, Canada. jolyane.meloche@criucpq.ulaval.ca.
authors.forename: Jolyane
authors.initials: J
authors.lastname: Meloche
authors.affiliation: Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Qu&#233;bec, Universit&#233; Laval, Qu&#233;bec City, QC G1V 4G5, Canada. rpaulin@ualberta.ca.
authors.forename: Roxane
authors.initials: R
authors.lastname: Paulin
authors.affiliation: Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Qu&#233;bec, Universit&#233; Laval, Qu&#233;bec City, QC G1V 4G5, Canada. olivier.boucherat@criucpq.ulaval.ca.
authors.forename: Olivier
authors.initials: O
authors.lastname: Boucherat
authors.affiliation: Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Qu&#233;bec, Universit&#233; Laval, Qu&#233;bec City, QC G1V 4G5, Canada. Steve.Provencher@criucpq.ulaval.ca.
authors.forename: Steeve
authors.initials: S
authors.lastname: Provencher
authors.affiliation: Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Qu&#233;bec, Universit&#233; Laval, Qu&#233;bec City, QC G1V 4G5, Canada. Sebastien.Bonnet@criucpq.ulaval.ca.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bonnet
mesh_terms: D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D050259:Genes, Mitochondrial; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress
keywords: DNA damage; DNA-damage response; inflammation; oxidative stress; pulmonary hypertension