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人心脏衰竭中AT1和AT2血管紧张素受体基因表达

AT1 and AT2 angiotensin receptor gene expression in human heart failure.

作者信息

Haywood G A, Gullestad L, Katsuya T, Hutchinson H G, Pratt R E, Horiuchi M, Fowler M B

机构信息

Division of Cardiovascular Medicine, Stanford (Calif) University, USA.

出版信息

Circulation. 1997 Mar 4;95(5):1201-6. doi: 10.1161/01.cir.95.5.1201.

DOI:10.1161/01.cir.95.5.1201
PMID:9054850
Abstract

BACKGROUND

The availability of selective antagonists for angiotensin II receptors has focused interest on the gene expression of angiotensin II-receptor subtypes in the human heart.

METHODS AND RESULTS

We analyzed expression of the AT1 and AT2 subtypes of the angiotensin II receptor in ventricular myocardium taken from 9 donor hearts before implantation and from 12 patients with heart failure (6 with dilated cardiomyopathy and 6 with ischemic heart disease). Competitive reverse transcription-polymerase chain reaction with synthetic RNA internal standards was used to detect mRNA for both subtypes and to quantify relative differences in levels between failing and non-failing ventricular myocardium. AT1- and AT2-receptor mRNA could be detected in all samples. AT1-receptor gene expression was 2.5-fold greater in nonfailing hearts than in patients with failing hearts (P = .015). There was no significant difference in AT2-receptor mRNA expression in failing and nonfailing hearts.

CONCLUSIONS

The level of expression of the angiotensin AT1 receptor appears to decrease in the failing human ventricle whereas the level of AT2 expression is unaffected. These changes parallel the changes found in human ventricular myocardium at the receptor level, suggesting that the changes in receptor level may result from changes in gene expression or mRNA stability.

摘要

背景

血管紧张素II受体选择性拮抗剂的出现使人们关注血管紧张素II受体亚型在人心脏中的基因表达。

方法与结果

我们分析了9例供体心脏植入前及12例心力衰竭患者(6例扩张型心肌病患者和6例缺血性心脏病患者)心室心肌中血管紧张素II受体AT1和AT2亚型的表达。采用竞争性逆转录聚合酶链反应及合成RNA内标来检测两种亚型的mRNA,并定量分析衰竭和非衰竭心室心肌之间水平的相对差异。所有样本均可检测到AT1和AT2受体mRNA。非衰竭心脏中AT1受体基因表达比衰竭心脏患者高2.5倍(P = 0.015)。衰竭和非衰竭心脏中AT2受体mRNA表达无显著差异。

结论

在衰竭的人心室中,血管紧张素ATl受体的表达水平似乎降低,而AT2受体表达水平未受影响。这些变化与在人心室心肌中受体水平发现的变化相似,提示受体水平的变化可能是基因表达或mRNA稳定性改变的结果。

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