Department of Pharmacology, University of Athens, 75 Mikras Asias Ave, 11527, Goudi, Athens, Greece.
Mol Cell Biochem. 2010 Dec;345(1-2):161-9. doi: 10.1007/s11010-010-0569-4. Epub 2010 Aug 22.
It has been previously shown that regulators of physiological growth such as thyroid hormone (TH) can favorably remodel the post ischaemic myocardium. Here, we further explored whether this effect can be preserved in the presence of co-morbidities such as diabetes which accelerates cardiac remodeling and increases mortality after myocardial infarction. Acute myocardial infarction (AMI) was induced by left coronary ligation in rats with type I diabetes (DM) induced by streptozotocin administration (STZ; 35 mg/kg; i.p.) while sham-operated animals served as controls (SHAM). AMI resulted in distinct changes in cardiac function and geometry; EF% was significantly decreased in DM-AMI [37.9 ± 2.0 vs. 74.5 ± 2.1 in DM-SHAM]. Systolic and diastolic chamber dimensions were increased without concomitant increase in wall thickness and thus, wall tension index [WTI, the ratio of (Left Ventricular Internal Diameter at diastole)/2*(Posterior Wall thickness)], an index of wall stress, was found to be significantly increased in DM-AMI; 2.27 ± 0.08 versus 1.70 ± 0.05. 2D-Strain echocardiographic analysis showed reduced systolic radial strain in all segments, indicating increased loss of cardiac myocytes in the infarct related area and less compensatory hypertrophy in the viable segments. This response was accompanied by a marked decrease in the expression of TRα1 and TRβ1 receptors in the diabetic myocardium without changes in circulating T3 and T4. Accordingly, the expression of TH target genes related to cardiac contractility was altered; β-MHC and PKCα were significantly increased. TH (L-T4 and L-T3) administration prevented these changes and resulted in increased EF%, normal wall stress and increased systolic radial strain in all myocardial segments. Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics.
先前的研究表明,甲状腺激素(TH)等生理生长调节剂可有利地重塑缺血后的心肌。在这里,我们进一步探讨了这种效应是否可以在合并症(如糖尿病)存在的情况下保留下来,糖尿病会加速心脏重塑并增加心肌梗死后的死亡率。通过链脲佐菌素(STZ;35mg/kg;腹腔注射)诱导的 1 型糖尿病(DM)大鼠左冠状动脉结扎诱导急性心肌梗死(AMI),而假手术操作的动物作为对照(SHAM)。AMI 导致心脏功能和几何形状发生明显变化;DM-AMI 中的 EF%显著降低[37.9±2.0 比 DM-SHAM 中的 74.5±2.1]。收缩和舒张室腔尺寸增加,而壁厚度没有相应增加,因此,壁张力指数(WTI,左心室舒张期内径/2*(后壁厚度)的比值),作为壁应力的指标,在 DM-AMI 中显著增加;2.27±0.08 比 1.70±0.05。二维应变超声心动图分析显示,所有节段的收缩径向应变均降低,表明梗死相关区域的心肌细胞丢失增加,而存活节段的代偿性肥大减少。这种反应伴随着糖尿病心肌中 TRα1 和 TRβ1 受体表达的显著减少,而循环 T3 和 T4 没有变化。相应地,与心脏收缩性相关的 TH 靶基因的表达发生改变;β-MHC 和 PKCα 显著增加。TH(L-T4 和 L-T3)给药可预防这些变化,并导致 EF%增加,壁应力正常和所有心肌节段的收缩径向应变增加。糖尿病大鼠的急性心肌梗死导致 TH 受体下调,具有重要的生理后果。TH 治疗可预防这种反应并改善心脏血液动力学。