OVEREXPRESSION OF THE RAT INDUCIBLE 70-KD HEAT-STRESS PROTEIN IN A TRANSGENIC MOUSE INCREASES THE RESISTANCE OF THE HEART TO ISCHEMIC-INJURY
OVEREXPRESSION OF THE RAT INDUCIBLE 70-KD HEAT-STRESS PROTEIN IN A TRANSGENIC MOUSE INCREASES THE RESISTANCE OF THE HEART TO ISCHEMIC-INJURY
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DOI：
10.1172/jci117815
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发表时间：
1995-04-01
影响因子：
15.9
通讯作者：
DILLMANN, WH
中科院分区：
文献类型：
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作者：
MARBER, MS;MESTRIL, R;DILLMANN, WH
全身热应激对心肌的保护作用和基因表达的变化，间接证据表明，一种诱导性70-kD热休克蛋白（hsp70i）在全身热应激下显著增加，有助于心肌保护。转基因阳性小鼠在全身热应激后心肌hsp70i的表达水平高于转基因阴性小鼠，这种高水平的表达没有明显的有害影响。对转基因阳性小鼠和转基因阴性小鼠的心脏进行Langendorff灌注，并进行20分钟的热（37℃）零流缺血和120分钟的再流，同时测量收缩恢复和肌酸激酶外排。心肌梗死以三苯四唑为界。与转基因阴性心脏相比，在转基因阳性心脏中，梗死区域减少了40%，30min回流时收缩功能增加了一倍，肌酸激酶外溢减少了50%。我们的研究结果首次表明，心肌hsp70i表达增加可以保护心脏免受缺血性损伤，并且hsp70i的抗缺血性特性可能具有治疗相关性。
Myocardial protection and changes in gene expression follow whole body heat stress, Circumstantial evidence suggests that an inducible 70-kD heat shock protein (hsp70i), increased markedly by whole body heat stress, contributes to the protection, Transgenic mouse lines were constructed with a cytomegalovirus enhancer and beta-actin promoter driving rat hsp70i expression in heterozygote animals, Unstressed, transgene positive mice expressed higher levels of myocardial hsp70i than transgene negative mice after whole body heat stress, This high level of expression occurred without apparent detrimental effect, The hearts harvested from transgene positive mice and transgene negative littermates were Langendorff perfused and subjected to 20 min of warm (37 degrees C) zero-flow ischemia and up to 120 min of reflow while contractile recovery and creatine kinase efflux were measured, Myocardial infarction was demarcated by triphenyltetrazolium. In transgene positive compared with transgene negative hearts, the zone of infarction was reduced by 40%, contractile function at 30 min of reflow was doubled, and efflux of creatine kinase was reduced by similar to 50%, Our findings suggest for the first time that increased myocardial hsp70i expression results in protection of the heart against ischemic injury and that the antiischemic properties of hsp70i have possible therapeutic relevance.