Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
PLoS One. 2011;6(5):e19922. doi: 10.1371/journal.pone.0019922. Epub 2011 May 19.
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.
尽管磷酸二酯酶 5（PDE5）早已被认为会影响平滑肌生物学，但最近的研究表明，它也在心肌中表达。鉴于对 PDE5 在心肌肥厚中的调节作用了解甚少，我们评估了猫肥厚模型左、右心室中 PDE5 表达和环鸟苷酸依赖性激酶 I（cGKI）水平的反应。
方法/主要发现：我们使用猫主动脉平滑肌细胞的 cDNA 文库，首次在该物种中鉴定和克隆了 PDE5 cDNA。该序列在氨基酸水平上与人的同源物具有 98%的同一性。克隆等位基因的大肠杆菌表达允许选择具有适当特异性的抗体，从而促进了在选择性近端主动脉（Ao）或肺动脉（PA）结扎创建的猫模型中 PDE5 表达的分析，这导致左心室（LV）和右心室（RV）分别发生肥厚。我们证明，PDE5 表达在 Ao 结扎模型中以 LV 表达降低和 RV 表达增加的方式表现出差异反应。同样，在 PA 结扎模型中，LV 的表达减少，而 RV 的表达不变。此外，Ao 结扎组 RV 中的 cGKI 表达显著降低，与 PDE5 表达的增加呈负相关。
结论/意义：PDE5 和 cGKI 表达的差异调节表明，在 RV 与 LV 中涉及的肥厚机制可能不同。Ao 结扎模型 RV 中 PDE5 和 cGKI 的相互表达表明 PDE5 上调具有功能意义。
