Omura T, Yoshiyama M, Takeuchi K, Hanatani A, Kim S, Yoshida K, Izumi Y, Iwao H, Yoshikawa J
First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
Basic Res Cardiol. 2000 Aug;95(4):316-23. doi: 10.1007/s003950070051.
In non-infarcted myocardium after myocardial infarction, the change of cardiac phenotypic modulation of contractile protein, extracellular matrix and intracellular Ca2+ transport protein, such as sarcoplasmic reticulum Ca2+(SR-Ca2+)-ATPase, Na+-Ca2+ exchanger, have a important role during cardiac remodeling. However, the time course in this gene expression in the adjacent and remote left ventricular, or right ventricular myocardium after myocardial infarction has not been well examined. The purpose of this study was to examine the left ventricular function and regional cardiac gene expression after myocardial infarction. Myocardial infarction was produced in Wistar rats by the ligation of the left anterior descending coronary artery. After 3 weeks, 2 months and 4 months from myocardial infarction, we performed Doppler echocardiography and measured the systolic and diastolic function. Then, we analyzed the contractile protein, extracellular matrix and intracellular Ca2+ transport protein mRNAs of cardiac tissues in the adjacent and the remote noninfarcted myocardium, and right ventricular myocardium by Northern blot hybridization. Fractional shortening of infarcted heart progressively decreased. Peak early diastolic filling wave (E wave) velocity increased, and the deceleration rate of the E wave velocity was more rapid in myocardial infarction areas. Atrial filling wave (A wave) velocity decreased, resulting in a marked increase in the ratio of E wave to A wave velocity. Expression of myocardial alpha-skeletal actin, beta-MHC and ANP mRNA, or collagen I and III mRNA were higher at 3 weeks after myocardial infarction. SR Ca2+-ATPase mRNA in the adjacent non-infarcted myocardium was decreased at 2 months, and that in remote myocardium was decreased at 4 months after infarction. Na+-Ca2+ exchanger mRNA levels were increased at 3 weeks, but was decreased at 2 months in the adjacent non-infarcted myocardium and at 4 months in the remote myocardium. These findings suggest that the compensation for myocardial infarction by myocardial gene expression in non-infarcted myocardium may occur at an early phase after myocardial infarction, and myocardial dysfunction may begin from adjacent to remote non-infarcted myocardium during progressive cardiac remodeling.
在心肌梗死后的非梗死心肌中，收缩蛋白、细胞外基质和细胞内Ca2+转运蛋白（如肌浆网Ca2+(SR-Ca2+)-ATP酶、Na+-Ca2+交换体）的心脏表型调节变化在心脏重塑过程中起重要作用。然而，心肌梗死后左心室相邻和远处或右心室心肌中该基因表达的时间进程尚未得到充分研究。本研究的目的是检测心肌梗死后左心室功能和局部心脏基因表达。通过结扎Wistar大鼠左前降支冠状动脉制造心肌梗死模型。心肌梗死后3周、2个月和4个月，我们进行了多普勒超声心动图检查并测量了收缩和舒张功能。然后，我们通过Northern印迹杂交分析了相邻和远处非梗死心肌以及右心室心肌组织中收缩蛋白、细胞外基质和细胞内Ca2+转运蛋白的mRNA。梗死心脏的缩短分数逐渐降低。早期舒张充盈波（E波）峰值速度增加，且心肌梗死区域E波速度的减速更快。心房充盈波（A波）速度降低，导致E波与A波速度比值显著增加。心肌α-骨骼肌肌动蛋白、β-肌球蛋白重链和心钠素mRNA或I型和III型胶原mRNA的表达在心肌梗死后3周时较高。相邻非梗死心肌中的SR Ca2+-ATP酶mRNA在梗死后2个月时降低，远处心肌中的该mRNA在梗死后4个月时降低。Na+-Ca2+交换体mRNA水平在3周时升高，但在相邻非梗死心肌中2个月时降低，在远处心肌中4个月时降低。这些发现表明，非梗死心肌中的心肌基因表达对心肌梗死的代偿可能在心肌梗死后早期发生，并且在进行性心脏重塑过程中，心肌功能障碍可能从相邻的非梗死心肌发展至远处的非梗死心肌。
