More severe cellular phenotype in human idiopathic dilated cardiomyopathy compared to ischemic heart disease.
More severe cellular phenotype in human idiopathic dilated cardiomyopathy compared to ischemic heart disease.
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DOI：
10.1007/s10974-010-9231-8
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发表时间：
2010-12
影响因子：
2.7
通讯作者：
van der Velden, Jolanda
中科院分区：
文献类型：
--
作者：
Hamdani, Nazha;Borbely, Attila;Veenstra, Sophie P. G. R.;Kooij, Viola;Vrydag, Wim;Zaremba, Ruud;dos Remedios, Cris;Niessen, Hans W. M.;Michel, Martin C.;Paulus, Walter J.;Stienen, Ger J. M.;van der Velden, Jolanda
β-肾上腺素能受体（βAR）通路的激活是心脏通过蛋白激酶A（PKA）介导的细胞靶蛋白磷酸化增加心输出量的主要机制，其中的扰动可能导致心力衰竭时的心功能障碍。本研究对特发性心肌梗死患者β-AR通路的介质、肌丝特性和心脏结构进行了综合分析，（IDCM; n = 13）和缺血性（ISHD; n = 10）心肌病与非衰竭心脏相比（供体; n = 10），用于以下参数：βAR密度、G偶联受体激酶2和5、刺激性和抑制性G蛋白、PKA的肌丝靶点磷酸化、蛋白磷酸酶1、受磷蛋白、SERCA 2a和单个肌细胞收缩性。所有参数均表现出心力衰竭的预期变化，但其中大多数参数的变化程度在IDCM中大于ISHD。组织学分析还显示，与ISHD相比，IDCM中的胶原蛋白更高。βAR通路的改变在IDCM中比在ISHD中更明显，并且可能反映细胞蛋白质组成和功能的连续变化。我们的数据表明，细胞功能障碍是更严重的IDCM比ISHD。
Activation of the β-adrenergic receptor (βAR) pathway is the main mechanism of the heart to increase cardiac output via protein kinase A (PKA)-mediated phosphorylation of cellular target proteins, and perturbations therein may contribute to cardiac dysfunction in heart failure. In the present study a comprehensive analysis was made of mediators of the βAR pathway, myofilament properties and cardiac structure in patients with idiopathic (IDCM; n = 13) and ischemic (ISHD; n = 10) cardiomyopathy in comparison to non-failing hearts (donor; n = 10) for the following parameters: βAR density, G-coupled receptor kinases 2 and 5, stimulatory and inhibitory G-proteins, phosphorylation of myofilament targets of PKA, protein phosphatase 1, phospholamban, SERCA2a and single myocyte contractility. All parameters exhibited the expected alterations of heart failure, but for most of them the extent of alteration was greater in IDCM than in ISHD. Histological analysis also revealed higher collagen in IDCM compared to ISHD. Alterations in the βAR pathway are more pronounced in IDCM than in ISHD and may reflect sequential changes in cellular protein composition and function. Our data indicate that cellular dysfunction is more severe in IDCM than in ISHD.
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通讯作者：
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