Black, S. M., Kumar, S., Wiseman, D., Ravi, K., Wedgwood, S., Ryzhov, V., Fineman, J. R. (2007) Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide. Clinical Hemorheology and Microcirculation, 37 (1-2). pp. 111-120. ISSN 1386-0291
Abstract
An increasing number of studies implicate oxidative stress in the development of endothelial dysfunction and the pathogenesis of cardiovascular disease. Further, this oxidative stress has been shown to be associated with alterations in both the endothelin-1 (ET-1) and nitric oxide (NO) signaling pathways such that bioavailable NO is decreased and ET-1 signaling is potentiated. However, recent data, from our groups and others, have shown that oxidative stress, ET-1, and NO are co-regulated in a complex fashion that appears to be dependent on the cellular levels of each species. Thus, when ROS levels are transiently elevated, NO signaling is potentiated through transcriptional, post-transcriptional, and post-translational mechanisms. However, in pediatric pulmonary hypertensive disorders, when reactive oxygen species (ROS) increases are sustained by ET-1 mediated activation of smooth muscle cell ETA subtype receptors, NOS gene expression and NO signaling are reduced. Further, increases in oxidative stress can stimulate both the expression of the ET-1 gene and the secretion of the ET-1 peptide. Thus, this manuscript will review the available data regarding the interaction of NO, ET-1, and ROS in the endothelial dysfunction of pediatric pulmonary hypertension. In addition, we will suggest avenues of both basic and clinical research that will be important to develop novel pulmonary hypertension treatment and prevention strategies.
| Item Type: | Paper |
|---|---|
| Additional Information: | Meeting abstract |
| Uncontrolled Keywords: | pulmonary hypertension reactive oxygen species enzyme inhibition gene expression cell signaling SMOOTH-MUSCLE-CELLS SOLUBLE GUANYLATE-CYCLASE HYPOXEMIC RESPIRATORY-FAILURE CONVERTING ENZYME EXPRESSION RANDOMIZED CONTROLLED-TRIAL SUPEROXIDE ANION RELEASE CONGENITAL HEART-DEFECTS GUINEA-PIG LUNG ANTIOXIDANT ENZYMES |
| Subjects: | bioinformatics > genomics and proteomics > small molecules > nitric oxide diseases & disorders > pulmonary disease |
| CSHL Authors: | |
| Communities: | CSHL labs > Wigler lab |
| Depositing User: | CSHL Librarian |
| Date: | 2007 |
| Date Deposited: | 30 Nov 2011 21:24 |
| Last Modified: | 21 Mar 2018 15:33 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22971 |
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