Patients with end-stage congestive heart failure treated with β-adrenergic receptor antagonists have improved ventricular myocyte calcium regulatory protein abundance
Patients with end-stage congestive heart failure treated with β-adrenergic receptor antagonists have improved ventricular myocyte calcium regulatory protein abundance
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DOI：
10.1161/hc3401.095073
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发表时间：
2001-08-28
期刊：
影响因子：
37.8
通讯作者：
Houser, SR
中科院分区：
文献类型：
--
作者：
Kubo, H;Margulies, KB;Houser, SR
背景-钙处理蛋白的改变被认为是导致充血性心力衰竭(CBF)心功能恶化的错乱的钙瞬变的基础。对CHF患者的临床试验表明，使用β-肾上腺素能受体拮抗剂(BETAB)治疗可以改善心功能。方法和结果：比较移植时取出的10例心衰患者和44例心衰患者(心衰组)的心内钙调节蛋白的丰度。分析了BETAB治疗(BETAB-CHF)和非BETAB治疗(Non-BETAB-CHF)患者，以及4个亚组：缺血性心肌病(ICM，n=10)、非缺血性扩张型心肌病(DCM，n=10)、ICM+BETAB治疗(BETAB-ICM，n=12)和DCM+BETAB治疗(BETAB-DCM，n=12)。用Western印迹法检测肌浆网钙ATPase、磷蛋白和Na+-Ca+交换蛋白丰度。用Fluo-3测量了钙离子的瞬变。与非BETAB-CHF组相比，非BETAB-CHF组肌浆网Ca~(2+)-ATPase明显减少，而磷蛋白和Na~+-Ca~(2+)交换器无明显变化。BETAB-ICM组和BETAB-DCM组肌浆网Ca~(2+)-ATPase高于非BETAB-CHF组，与NF组无差异。非BETAB-CHF心肌细胞的Ca~(2+)瞬变峰明显小于NF心肌细胞，且延长。BETAB-CHF心肌细胞的钙瞬变持续时间比BETAB-CHF心肌细胞短。结论BETAB治疗CHF患者可使心肌细胞内钙调节蛋白的丰度正常化，改善对钙的处理。
Background-Alterations in Ca2+-handling proteins are thought to underlie the deranged Ca2+ transients that contribute to deterioration of cardiac function in congestive heart failure (CBF). Clinical trials in CHF patients have shown that treatment with beta -adrenergic receptor antagonists (betaB) improves cardiac performance. The present study determined whether the abundance of Ca2+-handling proteins is different in failing hearts from patients treated or untreated with betaB.Methods and Results-Ca2+ regulatory protein abundance was compared in LV myocardium of 10 nonfailing hearts (NF group) and 44 failing hearts (CHF group) removed at transplantation. Analysis was performed in betaB-treated (betaB-CHF) and non-betaB treated (non-betaB-CHF) patients and in 4 subgroups: ischemic cardiomyopathy (ICM, n = 10), nonischemic dilated cardiomyopathy (DCM, n = 10), ICM with betaB therapy (betaB-ICM, n = 12), and DCM with betaB therapy (betaB-DCM, n = 12 n = 12). Sarcoplasmic reticulum Ca2+ ATPase, phospholamban, and Na+-Ca+ exchanger protein abundance were determined by use of Western blot analysis. Ca2+ transients were measured with fluo-3. Sarcoplasmic reticulum Ca2+ ATPase was significantly less abundant whereas phospholamban and Na+-Ca2+ exchanger were not significantly altered in non-betaB-CHF versus NF. Sarcoplasmic reticulum Ca2+ ATPase in the betaB-ICM and betaB-DCM was greater than in non-betaB-CHF and were not different than in NF. Ca2+ transients in non-betaB-CHF myocytes had significantly smaller peaks and were prolonged versus NF myocytes. Ca2+ transients from betaB-CHF myocytes had shorter durations than in betaB-CHF myocytes.Conchtsions-betaB treatment in CHF patients can normalize the abundance of myocyte Ca2+ regulatory proteins and improve Ca2+-handling.