S-Nitrosylation and the Development of Pulmonary Hypertension
Abstract
Pulmonary arterial hypertension (PAH), high blood pressure within the lung, is a progressive disease which is characterized by an increase in pulmonary arterial pressure and the formation of muscle around normally non-muscular small pulmonary arteries. Without treatment, PAH progresses rapidly to right heart failure and death. The mechanism(s) sensing the initiating event and transducing this signal into changes in protein expression to alter pulmonary physiology are unclear. The role S-nitrosothiols (SNO) play in the development of PAH is examined in this research project. In the pulmonary circulation, erythrocytes deliver SNOs to recipient target proteins on the surface of the endothelium as a function of oxygen saturation. In this context, erythrocytes can act as a molecular switch, monitoring changes in oxygen saturation to deliver SNOs to the vascular endothelium. We have developed a model in which Nacetyl cysteine (NAC) is used as a tracer to 1) monitor SNO formation, transfer and metabolism in vivo, 2) address the physiological and pathological consequences of SNO signaling in the pulmonary vasculature, and 3) identify SNO target proteins in this signaling pathway. Differences in SNO formation, transfer and metabolism and the role this pathway plays in gender specific differences associated with the development of PAH are examined. Studies for this grant period have focused on 1) defining the physiological pulmonary responses of S-nitrosothiols in female mice using our NAC model; 2) analyzing the physiological responses to S-nitrosothiols using mice deficient and null for proteins known to be involved in the formation and metabolism of Snitrosothiols and 3) identifying proteins and protein/protein interactions in the endothelium that are involved in this pathway.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 14, 2009
- Accession Number
- ADA500952
Entities
People
- Lisa A. Palmer
Organizations
- University of Virginia