Abstract:
BACKGROUND: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 RESULTS:Adenylyl 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. CONCLUSIONS:Unique 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.
journal_name
J Card Failjournal_title
Journal of cardiac failureauthors
Nakano SJ,Sucharov J,van Dusen R,Cecil M,Nunley K,Wickers S,Karimpur-Fard A,Stauffer BL,Miyamoto SD,Sucharov CCdoi
10.1016/j.cardfail.2016.07.429subject
Has Abstractpub_date
2017-01-01 00:00:00pages
72-80issue
1eissn
1071-9164issn
1532-8414pii
S1071-9164(16)31038-7journal_volume
23pub_type
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pub_type: 杂志文章,评审
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更新日期:2007-10-01 00:00:00
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