Issue title: Selected Papers from 1st Meeting on “Cardiovascular Biology: Endothelial Cell in Health and Hypertension”, 30 June–1 July 2006, Prague, Czech Republic
Article type: Research Article
Authors: Black, Stephen M.; | Kumar, Sanjiv | Wiseman, Dean | Ravi, Kandasamy | Wedgwood, Stephen | Ryzhov, Victor | Fineman, Jeffrey R.;
Affiliations: Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA | Cold Spring Harbor Laboratories, Cold Spring Harbor, NY 11724, USA | Department of Pediatrics, Northwestern University Medical School, Chicago, IL 60611, USA | Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA | Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA | Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA
Note: [] Corresponding author: Stephen M. Black, PhD, Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd, CB3210B, Augusta, GA 30912, USA. E-mail: sblack@mcg.edu.
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.
Keywords: Pulmonary hypertension, reactive oxygen species, enzyme inhibition, gene expression, cell signaling
Journal: Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 111-120, 2007
