Increased Messenger RNA Level of the Inhibitory G Protein α Subunit Giα‐2in Human End‐Stage Heart Failure
作者:
Thomas Eschenhagen,
Ulrike Mende,
Monika Nose,
Wilhelm Schmitz,
Hasso Scholz,
Axel Haverich,
Stefan Hirt,
Volker Döring,
Peter Kalmár,
Wolfgang Höppner,
Hans-Jörg Seitz,
期刊:
Circulation Research
(OVID Available online 1992)
卷期:
Volume 70,
issue 4
页码: 688-696
ISSN:0009-7330
年代: 1992
出版商: OVID
关键词: heart failure;G proteins;mRNA expression
数据来源: OVID
摘要:
In human heart failure the positive inotropic and cAMP-elevating effects of both β-adrenoceptor agonists and phosphodiesterase inhibitors are diminished. This has been explained at least in part by an increase in the inhibitory signal-transducing G protein (Gi) and unchanged stimulatory G protein (Gs). In the present study we determined the mRNA expression pattern of the α subunits of Gi-1, Gi-2, Gi-3, and Gsin myocardial tissue samples of patients undergoing heart transplantation. Northern blot analysis of total RNA extracted from left ventricles with32P-labeled cDNAs demonstrated expression of Giα-2, Giα-3, and Gsα. mRNA. In contrast, Giα-1mRNA was not detectable. To investigate whether the increased ratio of Gi/Gsmight be due to altered gene expression, we compared mRNA levels of Giα-2, Giα-3, and Gsαin left ventricular myocardium from failing hearts with idiopathic dilated cardiomyopathy (n=8) and ischemic cardiomyopathy (n=6) and from nonfailing hearts from transplant donors (n=8). Compared with nonfailing control hearts, the Giα-2mRNA was increased by 75±26% (p<0.05) in idiopathic dilated cardiomyopathy hearts and 90±26% (p<0.05) in ischemic cardiomyopathy hearts. Giα.3and GsαmRNA levels were similar in the three groups. The results suggest that as in other mammalian species, Giα-2and Giα-3, mRNA are the predominant GiαmRNA subtypes in human ventricular myocardium. An upregulation of Giα-2but not of Giα-3mRNA probably underlies the increase in Giαprotein and might thus be involved in the pathophysiological process leading to reduced responsiveness to cAMP-increasing agents in end-stage heart failure.
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