Alteration of growth responses in established cardiac pressure overload hypertrophy in rats with aortic banding.
Alteration of growth responses in established cardiac pressure overload hypertrophy in rats with aortic banding.
复制标题
主动脉束带大鼠已确定的心脏压力超负荷肥大中生长反应的改变。
DOI：
10.1172/jci118346
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Lorell,BH
中科院分区：
文献类型：
--
作者：
Schunkert,H;Weinberg,EO;Bruckschlegel,G;Riegger,AJ;Lorell,BH
我们研究了室壁压力升高、去甲肾上腺素和血管紧张素II对压力超负荷左心室肥厚心脏蛋白质合成和原癌基因表达的急性影响。对升主动脉缩窄后12 wk的慢性肥厚(LVH)大鼠心脏收缩功能完全维持时的心脏进行研究。灌流3h后分析新的蛋白质合成(掺入[~3H]苯丙氨酸[Phe])，并检测c-fos、c-jun、c-myc和早期生长反应基因-1(EGR-1)的mRNA水平(Northern印迹)。在基线条件下(即机械或神经激素刺激前)，年龄匹配的对照组和LVH心脏的[~3H]-Phe掺入(280nmoles/g蛋白/h)和原癌基因mRNA水平相似。然而，与非肥厚对照心脏相比，慢性LVH患者在急性施加等容收缩负荷(90毫米汞柱/克左心室)、去甲肾上腺素(10(-6)M)或血管紧张素II(10(-8)M+哌唑嗪10(-7)M)后，[~3H]-Phe掺入明显钝化或缺失。同样，急性收缩负荷或去甲肾上腺素刺激左心室肥厚的心脏，与对照心脏相比，原癌基因信使核糖核酸水平显著降低。左心室肥厚心脏c-fos mRNA的钝化诱导不是由于反馈抑制，因为环己酰亚胺灌流暴露于高壁应力的心脏进一步增加了年龄匹配的对照和左心室肥厚心脏之间的差异。这些数据表明，与非肥厚的对照心脏相比，对机械刺激或神经激素刺激的急性分子生长反应在有左室肥厚的大鼠心脏中发生了改变。这种代偿性肥厚心脏分子适应性的改变可能会防止对机械和神经激素刺激的不适当过度心脏生长。
We examined the acute effects of elevated wall stress, norepinephrine, and angiotensin II on cardiac protein synthesis as well as protooncogene expression in hearts with established pressure overload left ventricular hypertrophy. Isolated rat hearts with chronic hypertrophy (LVH) were studied 12 wk after ascending aortic banding when systolic function was fully maintained. New protein synthesis (incorporation of [3H]phenylalanine [Phe]) was analyzed in isolated perfused rat hearts after a 3-h protocol; c-fos, c-jun, c-myc, and early growth response gene-1 (EGR-1) mRNA levels (Northern blot) were studied over a time course from 15 to 240 min of perfusion. Under baseline conditions (i.e., before mechanical or neurohormonal stimulation), [3H]-Phe-incorporation (280 nmoles/gram protein/h) and protooncogene mRNA levels were similar in age-matched control and LVH hearts. However, hearts with chronic LVH were characterized by a markedly blunted or absent [3H]-Phe-incorporation after acute imposition of isovolumic systolic load (90 mmHg/gram left ventricle), as well as norepinephrine (10(-6)M), or angiotensin II infusion (10(-8)M plus prazosin 10(-7)M) compared with nonhypertrophied control hearts. Similarly, stimulation of LVH hearts with acute systolic load or norepinephrine was associated with a significantly blunted increase of protooncogene mRNA levels relative to control hearts. The blunted induction of c-fos mRNA in LVH hearts was not due to feedback inhibition, since cycloheximide perfusion of hearts exposed to elevated wall stress further increased the differences between age-matched control and LVH hearts. The data suggest that acute molecular growth responses to mechanical or neurohormonal stimulation are altered in rat hearts with established LVH relative to nonhypertrophied control hearts. This alteration of molecular adaptations in hearts with compensatory hypertrophy may prevent inappropriate excess cardiac growth in response to mechanical and neurohormonal stimuli.Images