Differential regulation of PDE5 expression in left and right ventricles of feline hypertrophy models
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Published on: September 25, 2017
Xiaoyin Shan1, Kenneth B Margulies
1Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
Insights
This study found that phosphodiesterase 5 (PDE5) expression changes differently in the left and right ventricles during cardiac hypertrophy in cats. This suggests distinct mechanisms regulate hypertrophy in each ventricle.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Enzyme Function
Background:
- Phosphodiesterase 5 (PDE5) is known to affect smooth muscle but is also expressed in the myocardium.
- The regulation of PDE5 in cardiac hypertrophy is not well understood.
- This study investigates PDE5 and cGMP-dependent kinase I (cGKI) in feline cardiac hypertrophy models.
Purpose of the Study:
- To assess PDE5 expression and cGKI levels in the left and right ventricles of feline hypertrophy models.
- To understand the differential regulation of PDE5 in cardiac hypertrophy.
- To explore the relationship between PDE5 and cGKI in hypertrophied ventricles.
Main Methods:
- Cloned feline PDE5 cDNA and developed specific antibodies.
- Created feline models of left ventricular (LV) and right ventricular (RV) hypertrophy via aortic (Ao) or pulmonary artery (PA) banding.
- Analyzed PDE5 and cGKI expression in hypertrophied LV and RV tissues.
Main Results:
- Feline PDE5 cDNA shares 98% amino acid identity with its human orthologue.
- PDE5 expression decreased in the LV and increased in the RV in the Ao-banding model.
- PDE5 expression decreased in the LV but remained unchanged in the RV in the PA-banding model.
- cGKI expression significantly decreased in the RV of the Ao-banded group, inversely correlating with PDE5 expression.
Conclusions:
- Differential regulation of PDE5 and cGKI suggests distinct hypertrophy mechanisms in the RV versus LV.
- Reciprocal PDE5 and cGKI expression in the RV of the Ao-banded model indicates functional significance for PDE5 up-regulation.
Background:
Though long known to affect smooth muscle biology, recent studies indicate that phosphodiesterase 5 (PDE5) is also expressed in myocardium. Recognizing that the regulation of PDE5 in hypertrophy is not well understood, we assessed the response of PDE5 expression and the level of cGMP-dependent kinase I (cGKI) in the left and right ventricles of feline hypertrophy models.
Methodology/Principal Findings:
Using a cDNA library of feline aortic smooth muscle cells, we identified and cloned PDE5 cDNA for the first time in this species. The sequence shares 98% identity with its human orthologue at the amino acid level. E. coli expression of the cloned allele allowed selection of antibodies with appropriate specificity, facilitating the analysis of PDE5 expression in feline models created by selective proximal aortic (Ao) or pulmonary artery (PA) banding that resulted in hypertrophy of the left ventricle (LV) and right ventricle (RV), respectively. We demonstrated that PDE5 expression responded differentially with a decreased expression in the LV and an increased expression in the RV in the Ao-banded model. Similarly, in the PA-banded model, LV showed reduced expression while the RV expression was unaltered. In addition, the expression of cGKI was significantly decreased in the RV of Ao-banded group, correlating inversely with the increase in PDE5 expression.
Conclusions/Significance:
The differential regulation of PDE5 and cGKI expression suggests that the mechanisms involved in hypertrophy could be different in RV vs. LV. Reciprocal PDE5 and cGKI expression in the RV of Ao-banded model suggests functional significance for PDE5 up-regulation.
