ALTERATIONS IN SARCOPLASMIC-RETICULUM GENE-EXPRESSION IN HUMAN HEART-FAILURE - A POSSIBLE MECHANISM FOR ALTERATIONS IN SYSTOLIC AND DIASTOLIC PROPERTIES OF THE FAILING MYOCARDIUM
ALTERATIONS IN SARCOPLASMIC-RETICULUM GENE-EXPRESSION IN HUMAN HEART-FAILURE - A POSSIBLE MECHANISM FOR ALTERATIONS IN SYSTOLIC AND DIASTOLIC PROPERTIES OF THE FAILING MYOCARDIUM
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DOI：
10.1161/01.res.72.2.463
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发表时间：
1993-02-01
影响因子：
20.1
通讯作者：
PERIASAMY, M
中科院分区：
文献类型：
--
作者：
ARAI, M;ALPERT, NR;PERIASAMY, M
最近的研究表明，细胞内钙处理是异常的终末期心力衰竭患者的心肌。衰竭心脏的肌肉表现出长时间的Ca 2+瞬变和降低的能力，以恢复低静息Ca 2+水平在心肌梗死。因此，我们研究了这种缺陷是否是由于Ca 2+转运功能的肌浆网基因表达的改变。我们测定了17例心脏移植受者的衰竭心脏中肌浆网钙转运蛋白的信使RNA（mRNA）水平，这些受者被诊断为扩张型心肌病、原发性肺动脉高压或缺血性心脏病。比较各组心钠素mRNA的表达水平，并与心钠素mRNA的表达水平进行相关分析。钙释放通道（ryanodine receptor，RYR 2）、钙摄取泵（Ca 2 +-ATP酶，SERCA 2亚型）和受磷蛋白的mRNA水平在心脏样本之间存在显著差异，但与心室心钠素mRNA呈负相关。相反，在这些衰竭的心脏中，钙螯合蛋白mRNA水平保持不变。此外，β-肌球蛋白和α-心肌肌动蛋白mRNA水平也显示出与ANF mRNA水平呈负相关。这些变化在患有扩张型心肌病、原发性肺动脉高压或缺血性心脏病所致充血性心力衰竭的心脏的右心室和左心室中均观察到。这些结果与以下假设一致：衰竭心脏肌浆网中钙处理异常是由于编码肌浆网蛋白的基因表达改变所致。
Recent studies have shown that intracellular Ca2+ handling is abnormal in the myocardium of patients with end-stage heart failure. Muscles from the failing hearts showed a prolonged Ca2+ transient and a diminished capacity to restore a low resting Ca2+ level during diastole. Accordingly, we examined whether this defect in Ca2+ transport function is due to alterations in sarcoplasmic reticulum gene expression. We determined the messenger RNA (mRNA) levels of sarcoplasmic reticulum Ca2+ transport proteins in failing human hearts from 17 cardiac transplant recipients with a diagnosis of dilated cardiomyopathy, primary pulmonary hypertension, or ischemic heart disease. The expression levels of each mRNA were compared with each other and then correlated with that of atrial natriuretic factor (ANF) mRNA in the failing ventricle. The mRNA levels for the calcium release channel (ryanodine receptor, RYR2), Ca2+ uptake pump (Ca2+-ATPase, SERCA2 isoform), and phospholamban differed significantly between heart samples but showed an inverse relation with that of ventricular ANF mRNA. In contrast, calsequestrin mRNA levels remained unchanged in these failing hearts. In addition, beta-myosin and alpha-cardiac actin mRNA levels also showed an inverse relation with ANF mRNA levels. These changes were observed in both right and left ventricles of hearts with congestive heart failure due to dilated cardiomyopathy, primary pulmonary hypertension, or ischemic heart disease. The results are consistent with the hypothesis that abnormal calcium handling in the sarcoplasmic reticulum of failing hearts is due to the altered expression of the genes encoding sarcoplasmic reticulum proteins.