Xu Y-J, Chapman D, Dixon I M C, Sethi R, Guo X, Dhalla N S
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine University of Manitoba, Winnipeg, Canada.
J Cell Mol Med. 2004 Jan-Mar;8(1):85-92. doi: 10.1111/j.1582-4934.2004.tb00262.x.
Post-myocardial infarction (MI) remodeling of cardiac myocytes and the myocardial interstitium results in alteration of gross ventricular geometry and ventricular dysfunction. To investigate the mechanisms of the remodeling process of the heart after large MI, the expression of various genes in viable left ventricle and infarct scar tissue were examined at 16 weeks post-MI. Steady-state expression of Na(+)-K+ ATPase alpha-1 and -2, phospholamban (PLB), alpha-myosin heavy chain (alpha-MHC), ryanodine receptor (Rya) and Ca2+ ATPase (Serca2) mRNAs were decreased in the infarct scar vs noninfarcted sham-operated controls (P < 0.05). On the other hand, Gialpha2 and beta-MHC mRNAs were upregulated (P < 0.05, respectively) in the infarct scar whereas Na(+)-K+ ATPase-beta, Na(+)-Ca2+ exchanger and Gs mRNAs were not altered vs control values. In viable left ventricle, the alpha-1 subunit of Na(+)-K+ ATPase, alpha-3, beta-isoforms, Rya, beta-MHC, Gialpha2, Gs and Na(+)-Ca2+ exchanger were significantly elevated while expression of the alpha-2 subunit of Na(+)-K+ ATPase, PLB and Serca2 were significantly decreased compared to controls. Expression of CK2alpha mRNA was elevated in noninfarcted heart (145 +/- 15%) and diminished in the infarct scar (66 +/- 13%) vs controls. Expression of beta-MHC mRNA was elevated in both viable and infarct scar tissues of experimental hearts (140 +/- 31% and 183 +/- 30% vs. controls, respectively). These results suggest that cardiac genes in the infarcted tissue and viable left ventricle following MI are differentially regulated.
心肌梗死后（MI）心肌细胞和心肌间质的重塑会导致心室整体几何形状改变和心室功能障碍。为了研究大面积心肌梗死后心脏重塑过程的机制，在心肌梗死后16周检测了存活左心室和梗死瘢痕组织中各种基因的表达。与未梗死的假手术对照组相比，梗死瘢痕中Na(+)-K+ ATP酶α-1和-2、受磷蛋白（PLB）、α-肌球蛋白重链（α-MHC）、兰尼碱受体（Rya）和Ca2+ ATP酶（Serca2）mRNA的稳态表达降低（P < 0.05）。另一方面，梗死瘢痕中Gialpha2和β-MHC mRNA上调（分别为P < 0.05），而Na(+)-K+ ATP酶-β、Na(+)-Ca2+交换体和Gs mRNA与对照值相比未改变。在存活的左心室中，与对照组相比，Na(+)-K+ ATP酶的α-1亚基、α-3、β-异构体、Rya、β-MHC、Gialpha2、Gs和Na(+)-Ca2+交换体显著升高，而Na(+)-K+ ATP酶α-2亚基、PLB和Serca2的表达显著降低。与对照组相比，非梗死心脏中CK2α mRNA表达升高（145 +/- 15%），梗死瘢痕中降低（66 +/- 13%）。实验心脏的存活组织和梗死瘢痕组织中β-MHC mRNA表达均升高（分别为140 +/- 31%和183 +/- 30% vs.对照组）。这些结果表明，心肌梗死后梗死组织和存活左心室中的心脏基因受到不同的调控。
