Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy
Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy
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DOI：
10.1172/jci119730
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发表时间：
1997-10-15
影响因子：
15.9
通讯作者：
Anversa, P
中科院分区：
文献类型：
--
作者：
Li, Q;Li, BS;Anversa, P
为了确定IGF-1是否对抗梗死后存活心肌中肌细胞死亡的刺激，对肌细胞中过表达人IGF-1B的转基因小鼠（FVB.Igf+/-）和1.5和2.5月龄的野生型同窝小鼠进行冠状动脉结扎，并在7天后处死。心肌梗死平均累及50%的左心室，并导致心力衰竭。非转基因组梗死区心肌细胞凋亡在1.5和2.5个月时分别增加4.2倍和2.1倍，相应的心肌细胞坏死分别增加1.8倍和1.6倍。相反，FVB.Igf+/-小鼠在梗死后任一年龄的凋亡和坏死性心肌细胞死亡均未增加。在2.5月龄的非转基因梗死患者中，功能损害与室壁厚度减少29%、室腔直径增加43%、室腔体积扩大131%相关。相反，FVB.Igf+/-梗死患者的室壁厚度、室腔直径和腔体积的变化分别比非转基因梗死患者小41%、58%和48%。FVB.Igf+/-小鼠对梗死的不同反应导致舒张期壁应力、心脏重量以及左心室和右心室重量-体重比的增加减弱。总之，IGF-1的组成性过表达阻止了梗死后存活心肌中细胞死亡的激活，限制了心室扩张、心肌负荷和心肌肥大。
To determine whether IGF-1 opposes the stimulation of myocyte death in the surviving myocardium after infarction, transgenic mice overexpressing human IGF-1B in myocytes (FVB.Igf+/-) and wild-type littermates at 1.5 and 2.5 mo of age were subjected to coronary ligation and killed 7 d later. Myocardial infarction involved an average 50% of the left ventricle, and produced cardiac failure, In the region proximate to infarction, myocyte apoptosis increased 4.2-fold and 2.1-fold in nontransgenics at 1.5 and 2.5 mo, respectively, Corresponding increases in myocyte necrosis were 1.8-fold and 1.6-fold. In contrast, apoptotic and necrotic myocyte death did not increase in FVB.Igf+/- mice at either age after infarction. In 2.5-mo-old infarcted nontransgenics, functional impairment was associated with a 29% decrease in wall thickness, 43% increase in chamber diameter, and a 131% expansion in chamber volume, Conversely, the changes in wall thickness, chamber diameter, and cavitary volume were 41, 58, and 48% smaller in infarcted FVB.Igf+/- than in nontransgenics. The differential response to infarction of FVB.Igf+/- mice resulted in an attenuated increase in diastolic wall stress, cardiac weight, and left and right ventricular weight-to-body wt ratios. In conclusion, constitutive overexpression of IGF-1 prevented activation of cell death in the viable myocardium after infarction, limiting ventricular dilation, myocardial loading, and cardiac hypertrophy.