Cardiac Adenylyl Cyclase and Phosphodiesterase Expression Profiles Vary by Age, Disease, and Chronic Phosphodiesterase Inhibitor Treatment.
Cardiac Adenylyl Cyclase and Phosphodiesterase Expression Profiles Vary by Age, Disease, and Chronic Phosphodiesterase Inhibitor Treatment.
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DOI：
10.1016/j.cardfail.2016.07.429
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发表时间：
2017-01
影响因子：
6
通讯作者：
Sucharov CC
中科院分区：
文献类型：
--
作者：
Nakano SJ;Sucharov J;van Dusen R;Cecil M;Nunley K;Wickers S;Karimpur-Fard A;Stauffer BL;Miyamoto SD;Sucharov CC
尽管磷酸二酯酶-3抑制剂（PDE 3 i）的使用比成人心力衰竭（HF）人群取得了更大的成功，但儿科心力衰竭（HF）患者对传统HF药物的反应不佳。我们假设HF患儿的特异性分子改变和HF病因可能影响治疗反应。采用实时定量聚合酶链反应技术对扩张型心肌病（DCM）成人、DCM儿童和右心室形态（SRV）单心室先天性心脏病儿童的心肌组织腺苷酸环化酶（AC）和磷酸二酯酶（PDE）亚型进行定量。AC和PDE表达谱在每个受试者组中受到独特的调节，并显示出对慢性PDE 3 i的响应的不同变化。在成人DCM中，PDE 3 i的AC 5（倍数变化2.415; P = 0.043）、儿科DCM中的AC 2（倍数变化2.396; P = 0.0067）和儿科SRV中的PDE 1C（倍数变化1.836; P = 0.032）存在独特的上调。值得注意的是，PDE 5A表达在所有年龄和疾病组中一致增加。AC和PDE亚型的独特调节支持与成人相比儿童对HF的不同分子适应，并可能有助于确定儿科HF发病机制的特异性机制。更好地了解这些差异将有助于根据年龄和疾病过程优化药物治疗。
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. 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. 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.