Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats.
Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats.
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DOI：
10.1186/1479-5876-11-40
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发表时间：
2013-02-14
影响因子：
7.4
通讯作者：
Gerdes AM
中科院分区：
文献类型：
--
作者：
Chen YF;Weltman NY;Li X;Youmans S;Krause D;Gerdes AM
尽管在过去的几十年里医学治疗取得了进步，但大面积透壁性心肌梗死（MI）后的左心室（LV）重构仍然是一个关键的临床问题。识别新的药物，以改善重塑过程，并防止心肌梗死后进展为心力衰竭是至关重要的。甲状腺激素（TH）已被证明可以改善心肌梗死后动物和人类的左心室功能和重塑。然而，TH治疗引起的潜在细胞重塑的变化尚不清楚。通过结扎左冠状动脉降支在成年雌性Sprague-Dawley大鼠中产生MI。用L-甲状腺素（T_4）微丸（3.3mg，60天缓释）治疗MI大鼠8周。在终末研究中测量非梗死区的孤立肌细胞形状、小动脉和胶原沉积。T4治疗改善了MI大鼠的LV ±dp/dt，使TAU正常化，并增加了心肌细胞横截面积，但未进一步增加心肌细胞长度。T4治疗使MI大鼠的总LV组织面积增加34%，非梗死组织面积增加41%，非梗死区厚度增加36%。然而，肌细胞体积仅占非梗死区肌细胞质量增加的约1/3，表明治疗后存在更多的肌细胞。T4给药倾向于增加与LV重量增加成比例的较小小动脉（5 - 15 μm）的总长度，并减少LV非梗死区域的胶原沉积。在T4处理的MI大鼠中也观察到金属蛋白酶-2（MMP-2）表达和金属蛋白酶组织抑制剂（TIMP）-1至4表达增加的趋势。这些结果表明，MI后长期T4治疗对非梗死区的肌细胞、小动脉和胶原基质重塑具有有益作用。最重要的是，结果表明改善了梗死周围区域的肌细胞存活。
Left ventricular (LV) remodeling following large transmural myocardial infarction (MI) remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs) have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear. MI was produced in adult female Sprague–Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4) pellet (3.3 mg, 60 days sustained release) was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study. T4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 μm) proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2) expression and tissue inhibitor of metalloproteinases (TIMPs) -1 to −4 expression was also observed in T4 treated MI rats. These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area.
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影响因子：
5.9
作者：
Friberg, L;Drvota, V;Ahnve, S
通讯作者：
Ahnve, S
DOI：
10.1016/j.carpath.2010.09.007
发表时间：
2011-09-01
期刊：
Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology
影响因子：
--
作者：
Chen, Yue-Feng;Redetzke, Rebecca A;Gerdes, Anthony Martin
通讯作者：
Gerdes, Anthony Martin
影响因子：
20.3
作者：
Collen, A;Hanemaaijer, R;van Hinsbergh, VWM
通讯作者：
van Hinsbergh, VWM
DOI：
10.1152/ajpendo.2000.279.6.e1319
发表时间：
2000-12-01
影响因子：
5.1
作者：
Ojamaa, K;Kenessey, A;Klein, I
通讯作者：
Klein, I
影响因子：
37.8
作者：
LITWIN, SE;LITWIN, CM;GOLDMAN, S
通讯作者：
GOLDMAN, S