Pantos Constantinos, Mourouzis Iordanis, Markakis Konstantinos, Tsagoulis Nikolaos, Panagiotou Matthew, Cokkinos Dennis V
Dept. of Pharmacology, University of Athens, 75 Mikras Asias Ave., Goudi, 11527, Athens, Greece.
Basic Res Cardiol. 2008 Jul;103(4):308-18. doi: 10.1007/s00395-008-0697-0. Epub 2008 Feb 15.
Thyroid hormone (TH) is critical for tissue differentiation at early stages of development, induces physiological hypertrophy and regulates the expression of important contractile proteins such as myosin heavy chain (MHC) isoform and calcium cycling proteins. Furthermore, TH seems to control the response to stress by regulating important cardioprotective molecules such as heat shock proteins (HSPs). Thus, the present study investigated whether TH administration immediately after acute myocardial infarction can favourably remodel the post-infarcted myocardium. Acute myocardial infarction was induced in rats by coronary artery ligation (AMI, n=10), while SHAM-operated animals served as controls (SHAM, n = 8). TH was administered for 13 weeks (AMI-THYR, n = 9). Cardiac contractile function and left ventricular (LV) chamber remodelling was assessed by serial echocardiography and in Langendorff heart preparations. AMI significantly reduced LV ejection fraction (EF%); 30.0 (s.e.m, 2.3) Vs. 73.8 (1.8) in SHAM, P < 0.05. In addition, +dp/dt and -dp/dt (in mmHg/s) were 4,051 (343) and 2,333 (118) respectively for SHAM Vs. 2,102 (290) and 1,368 (181) for AMI, P < 0.05. With TH treatment, EF% was increased to 49.5 (2.7) in AMI-THYR, P < 0.05, while +dp/dt and -dp/dt (in mmHg/s) were 3,708 (231) and 2,035 (95) for AMI-THYR, P < 0.05 Vs. AMI. A marked elevation of the expression of beta-MHC and a reduced ratio of SERCA/Phospholamban were found in viable myocardium of AMI hearts, which was prevented by TH. Furthermore, heat shock protein 70 myocardial content was decreased in AMI hearts and was significantly increased after TH treatment. An ellipsoidal reshaping of LV chamber was observed with TH; cardiac sphericity index, (ratio of long/short axis, SI), was 1.98 (0.03) for SHAM, 1.52 (0.05) for AMI and 1.72(0.02) for AMI-THYR, P < 0.05. In conclusion, long-term TH administration immediately after AMI results in sustained improvement of cardiac haemodynamics.
甲状腺激素（TH）在发育早期对组织分化至关重要，可诱导生理性肥大并调节重要收缩蛋白的表达，如肌球蛋白重链（MHC）亚型和钙循环蛋白。此外，TH似乎通过调节重要的心脏保护分子如热休克蛋白（HSPs）来控制对应激的反应。因此，本研究调查了急性心肌梗死后立即给予TH是否能有利地重塑梗死心肌。通过冠状动脉结扎诱导大鼠急性心肌梗死（AMI，n = 10），而假手术动物作为对照（SHAM，n = 8）。给予TH 13周（AMI - THYR，n = 9）。通过连续超声心动图和Langendorff心脏标本评估心脏收缩功能和左心室（LV）腔重塑。AMI显著降低了LV射血分数（EF%）；SHAM组为73.8（1.8），AMI组为30.0（标准误，2.3），P < 0.05。此外，SHAM组的 +dp/dt和 -dp/dt（单位：mmHg/s）分别为4,051（343）和2,333（118），而AMI组分别为2,102（290）和1,368（181），P < 0.05。TH治疗后，AMI - THYR组的EF%增加到49.5（2.7），P < 0.05，而AMI - THYR组的 +dp/dt和 -dp/dt（单位：mmHg/s）分别为3,708（231）和2,035（95），与AMI组相比P < 0.05。在AMI心脏的存活心肌中发现β - MHC表达明显升高，SERCA/受磷蛋白比值降低，而TH可预防这种情况。此外，AMI心脏中热休克蛋白70的心肌含量降低，TH治疗后显著增加。TH治疗后观察到LV腔呈椭圆形重塑；心脏球形指数（长轴/短轴比值，SI），SHAM组为1.98（0.03），AMI组为1.52（0.05），AMI - THYR组为1.72（0.02），P < 0.05。总之，AMI后立即长期给予TH可导致心脏血流动力学持续改善。
