PATHOGENIC ROLE OF PHOSPHODIESTERASE TYPE 5 UPREGULATION IN CARDIAC ISCHEMIA/REPERFUSION INJURY

Phosphodiesterase Type 5 (PDE5) inhibitors are cardioprotective against ischemia/reperfusion (I/R) injury. However, it remains uncertain if I/R affects PDE5. We hypothesized that generation of reactive oxygen species (ROS) during I/R leads to upregulation of PDE5, which contributes to pathological changes following acute myocardial infarction (AMI). Adult male ICR mice were subjected to 30 minutes of in vivo or ex vivo I/R. To examine the role of ROS, a subset of hearts were perfused with 100 µM hydrogen peroxide (H2O2). Expression and activity of PDE5, pPDE5, and cGMP-dependent protein kinase (PKG) were measured by Western blots and spectrophotometric assay. The results show that ischemia and I/R significantly increased expression of PDE5. H2O2 had no effect on PDE5 expression and activity but significantly increased PKG activity. We conclude that acute cardiac ischemia or I/R upregulate PDE5 independent of oxidant stress in the heart.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biochemistry

Year dc:date.available

2010

Author dc:creator

• Hobbs, Daniel

Contributors dc:contributor

• Rakesh Kukreja

• Phosphodiesterase 5
• Ischemia/Reperfusion Injury
• Reactive Oxygen Species
• Pharmacological Preconditioning
• cGMP-Dependent Protein Kinase
• Myocardial Infarction
• Biochemistry, Biophysics, and Structural Biology
• Life Sciences

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/106

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-1105