DNA Damage and Pulmonary Hypertension
AbstractPulmonary 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
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Ranchoux, B.; Meloche, J.; Paulin, R.; Boucherat, O.; Provencher, S.; Bonnet, S. DNA Damage and Pulmonary Hypertension. Int. J. Mol. Sci. 2016, 17, 990.
Ranchoux B, Meloche J, Paulin R, Boucherat O, Provencher S, Bonnet S. DNA Damage and Pulmonary Hypertension. International Journal of Molecular Sciences. 2016; 17(6):990.Chicago/Turabian Style
Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien. 2016. "DNA Damage and Pulmonary Hypertension." Int. J. Mol. Sci. 17, no. 6: 990.
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