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Int. J. Mol. Sci. 2016, 17(6), 990; doi:10.3390/ijms17060990

DNA Damage and Pulmonary Hypertension

Pulmonary Hypertension Research Group, Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, QC G1V 4G5, Canada
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Academic Editor: Guillermo T. Sáez
Received: 5 April 2016 / Revised: 1 June 2016 / Accepted: 16 June 2016 / Published: 22 June 2016
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases 2016)
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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. View Full-Text
Keywords: DNA damage; DNA-damage response; pulmonary hypertension; inflammation; oxidative stress DNA damage; DNA-damage response; pulmonary hypertension; inflammation; oxidative stress
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ranchoux, B.; Meloche, J.; Paulin, R.; Boucherat, O.; Provencher, S.; Bonnet, S. DNA Damage and Pulmonary Hypertension. Int. J. Mol. Sci. 2016, 17, 990.

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