Reactive oxygen species and antioxidants in pulmonary hypertension.
CONCLUSIONS
Pulmonary hypertension is a devastating disorder without any available treatment strategies that satisfactorily promote the survival of patients. The identification of new therapeutic strategies to treat patients with pulmonary hypertension is warranted.


BACKGROUND
Human studies have provided evidence that there is increased oxidative stress (lipid peroxidation, protein oxidation, DNA oxidation, and the depletion of small-molecule antioxidants) in patients with pulmonary hypertension. A variety of compounds with antioxidant properties have been shown to have beneficial therapeutic effects in animal models of pulmonary hypertension, possibly supporting the hypothesis that reactive oxygen species (ROS) are involved in the progression of pulmonary hypertension. Thus, understanding the molecular mechanisms of ROS actions could contribute to the development of optimal, antioxidant-based therapy for human pulmonary hypertension. One such mechanism includes action as a second messenger during cell-signaling events, leading to the growth of pulmonary vascular cells and right ventricular cells.


RESULTS
The molecular mechanisms behind promotion of cell signaling for pulmonary vascular cell growth and right ventricular hypertrophy by ROS are not well understood. Evidence suggests that iron-catalyzed protein carbonylation may be involved.


CONCLUSIONS
Understanding precise mechanisms of ROS actions should be useful for designing preclinical animal experiments and human clinical trials of the use of antioxidants and/or other redox compounds in the treatment of pulmonary hypertension.
Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057, USA.
Chi-Ming
CM
Wong
Geetanjali
G
Bansal
Ludmila
L
Pavlickova
Lucia
L
Marcocci
Yuichiro J
YJ
Suzuki
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000378:metabolism; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
D000975:Antioxidants; D017382:Reactive Oxygen Species; D007501:Iron