Arai M, Alpert N R, MacLennan D H, Barton P, Periasamy M
Department of Physiology and Biophysics, University of Vermont College of Medicine, Burlington.
Circ Res. 1993 Feb;72(2):463-9. doi: 10.1161/01.res.72.2.463.
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 (Ca(2+)-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.
近期研究表明，终末期心力衰竭患者心肌细胞内的钙处理存在异常。衰竭心脏的肌肉显示出钙瞬变延长，且在舒张期恢复低静息钙水平的能力减弱。因此，我们研究了这种钙转运功能缺陷是否归因于肌浆网基因表达的改变。我们测定了17名心脏移植受者衰竭人心脏中肌浆网钙转运蛋白的信使核糖核酸（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。将每种mRNA的表达水平相互比较，然后与衰竭心室中心房利钠因子（ANF）mRNA的表达水平进行关联分析。心脏样本中钙释放通道（雷诺丁受体，RYR2）、钙摄取泵（Ca(2+)-ATP酶，SERCA2亚型）和受磷蛋白的mRNA水平存在显著差异，但与心室ANF mRNA水平呈负相关。相比之下，在这些衰竭心脏中，肌集钙蛋白mRNA水平保持不变。此外，β-肌球蛋白和α-心肌肌动蛋白mRNA水平也与ANF mRNA水平呈负相关。在因扩张型心肌病、原发性肺动脉高压或缺血性心脏病导致充血性心力衰竭的心脏左右心室中均观察到了这些变化。这些结果与以下假设一致，即衰竭心脏肌浆网中异常的钙处理是由于编码肌浆网蛋白的基因表达改变所致。
