Cardiac Adenylyl Cyclase and Phosphodiesterase Expression Profiles Vary by Age, Disease, and Chronic Phosphodiesterase Inhibitor Treatment

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• 作者：Stephanie J. Nakano ; MD¹ ; Juliana Sucharov² ; Robert van Dusen ; BS³ ; Mackenzie Cecil² ; Karin Nunley ; MS⁴ ; Sean Wickers⁵ ; Anis Karimpur-Fard ; PhD⁶ ; Brian L. Stauffer ; MD⁴ ; ⁷ ; Shelley D. Miyamoto ; MD¹ ; Carmen C. Sucharov ; PhD⁴ ; ^{kika.sucharov@ucdenver.edu}
• 关键词：Adenylyl cyclase ; phosphodiesterase ; single ventricle congenital heart disease ; dilated cardiomyopathy
• 刊名：Journal of Cardiac Failure
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：23
• 期：1
• 页码：72-80
• 全文大小：162 K
• 卷排序：23

文摘

Pediatric heart failure (HF) patients have a suboptimal response to traditional HF medications, although phosphodiesterase-3 inhibition (PDE3i) has been used with greater success than in the adult HF population. We hypothesized that molecular alterations specific to children with HF and HF etiology may affect response to treatment.Methods and ResultsAdenylyl cyclase (AC) and phosphodiesterase (PDE) isoforms were quantified by means of quantitative real-time polymerase chain reaction in explanted myocardium from adults with dilated cardiomyopathy (DCM), children with DCM, and children with single-ventricle congenital heart disease of right ventricular morphology (SRV). AC and PDE expression profiles were uniquely regulated in each subject group and demonstratde distinct changes in response to chronic PDE3i. There was unique up-regulation of AC5 in adult DCM with PDE3i (fold change 2.415; P = .043), AC2 in pediatric DCM (fold change 2.396; P = .0067), and PDE1C in pediatric SRV (fold change 1.836; P = .032). Remarkably, PDE5A expression was consistently increased across all age and disease groups.ConclusionsUnique regulation of AC and PDE isoforms supports a differential molecular adaptation to HF in children compared with adults, and may help identify mechanisms specific to the pathogenesis of pediatric HF. Greater understanding of these differences will help optimize medical therapies based on age and disease process.