Yoshiyama M, Takeuchi K, Hanatani A, Kim S, Omura T, Toda I, Teragaki M, Akioka K, Iwao H, Yoshikawa J
First Department of Internal Medicine, Osaka City University Medical School, Japan.
J Mol Cell Cardiol. 1997 Jan;29(1):255-64. doi: 10.1006/jmcc.1996.0270.
Although cardiac failure can develop over time after myocardial infarction, the mechanism responsible for this is still unknown. The change of intracellular Ca2+ transport protein, such as sarcoplasmic reticulum (SR) Ca2+-ATPase (SR-Ca2+), Na+-Ca2+ exchanger (Na+-Ca2+), or cardiac phenotypic modulation of contractile protein in noninfarcted myocardium may have a important role. However, the time course in gene expression of sarcoplasmic reticulum (SR) Ca2+-ATPase (SR-Ca2+), Na+-Ca2+ exchanger (Na+-Ca2+), and contractile protein in the adjacent and remote noninfarcted myocardium after myocardial infarction has not been examined. At 1, 3 weeks and 3 months after myocardial infarction, hemodynamics were measured and mRNA of the left ventricle was analyzed. Left ventricular end-diastolic volume and weight increased both with time. Ascites became apparent at 3 months after infarction. SR-Ca2+ mRNA levels in the adjacent noninfarcted myocardium were 0.7- (P<0.01), 0.9- (N.S.), and 0.7-fold (P<0.01) of control, and Na+-Ca2+ mRNA levels were 2.1- (P<0.01), 1.4- (P<0.01), and 0.8-fold (P<0.01) of control, at 1, 3 weeks and 3 months after infarction, respectively. beta-Myosin heavy chain (MHC) mRNA was increased to 2.1- (P<0.01), 1.5- (P<0.01), and 1.4-fold (P<0.01), and alpha-skeletal actin was increased to 2.4- (P<0.01), 3.8- (P<0.01), and 1.6-fold (P<0.01) control levels, at 1 week, 3 weeks and 3 months, respectively. In contrast, alpha-MHC mRNA level was decreased at 1 week and 3 months after infarction. alpha-cardiac actin mRNA level did not change over time after infarction. In the remote non-infarcted myocardium, beta-MHC, alpha-skeletal actin, and Na+-Ca2+ mRNA levels were increased, but SR-Ca2+, alpha-MHC, and alpha-cardiac actin mRNA did not change after infarction. These findings suggest that: (1) intracellular Ca2+ handling system after myocardial infarction may be different between adjacent and remote non-infarcted myocardium: and that (2) both decreased gene expression of SR Ca2+-ATPase and Na+-Ca2+ exchanger in the adjacent non-infarcted myocardium may progress cardiac dysfunction.
虽然心肌梗死后心力衰竭可能会随时间发展,但其发病机制仍不清楚。细胞内钙转运蛋白的变化,如肌浆网(SR)钙 - 三磷酸腺苷酶(SR - Ca2+)、钠 - 钙交换体(Na+ - Ca2+),或梗死心肌外非梗死心肌中收缩蛋白的心脏表型调节可能起重要作用。然而,心肌梗死后相邻和远处非梗死心肌中肌浆网(SR)钙 - 三磷酸腺苷酶(SR - Ca2+)、钠 - 钙交换体(Na+ - Ca2+)和收缩蛋白的基因表达随时间的变化过程尚未得到研究。在心肌梗死后1周、3周和3个月,测量血流动力学并分析左心室的mRNA。左心室舒张末期容积和重量均随时间增加。梗死后3个月出现腹水。梗死1周、3周和3个月时,相邻非梗死心肌中SR - Ca2+ mRNA水平分别为对照组的0.7倍(P<0.01)、0.9倍(无显著性差异)和0.7倍(P<0.01),Na+ - Ca2+ mRNA水平分别为对照组的2.1倍(P<0.01)、1.4倍(P<0.01)和0.8倍(P<0.01)。β - 肌球蛋白重链(MHC)mRNA在梗死后1周、3周和3个月时分别增加到对照组的2.1倍(P<0.01)、1.5倍(P<0.01)和1.4倍(P<0.01),α - 骨骼肌肌动蛋白分别增加到对照组的2.4倍(P<0.01)、3.8倍(P<0.01)和1.6倍(P<0.01)。相比之下,梗死后1周和3个月时α - MHC mRNA水平降低。梗死后α - 心肌肌动蛋白mRNA水平未随时间变化。在远处非梗死心肌中,β - MHC、α - 骨骼肌肌动蛋白和Na+ - Ca2+ mRNA水平升高,但梗死后SR - Ca2+、α - MHC和α - 心肌肌动蛋白mRNA未发生变化。这些发现表明:(1)心肌梗死后相邻和远处非梗死心肌的细胞内钙处理系统可能不同;(2)相邻非梗死心肌中SR钙 - 三磷酸腺苷酶和钠 - 钙交换体基因表达的降低可能会导致心脏功能障碍。