Copyright © 2001 by the European Society of Cardiology.
Expression of RGS3, RGS4 and Gi alpha 2 in acutely failing donor hearts and end-stage heart failure
National Heart and Lung Institute at Imperial College School of Medicine, London, U.K.
revised December 12, 2000; accepted December 14, 2000
Abstract
Background Regulators of G-protein Signalling (RGS) proteins have been shown to limit in vitro signalling of G proteins. In common with end-stage heart failure, we have recently shown that upregulation of the inhibitory G-protein, Gi
, occurs in acutely failing donor hearts unused for transplantation due to severe myocardial dysfunction. In light of recent data on RGS proteins, we have evaluated mRNA and protein expression of RGS3, RGS4 and Gi2 in the myocardium from normal, end-stage failing and acutely failing unused donor hearts.
Methods and Results Myocardial samples were obtained from end-stage failing hearts explanted prior to transplantation (n=19), unused donor hearts with ejection fractions <30% (n=14) and used donor hearts with good function (ejection fraction >60%) (n=4–7). mRNA levels were quantified using quantitative reverse transcriptase polymerase chain reaction. Levels of RGS3 and RGS4 mRNA were found to be significantly upregulated in unused donor and end-stage failing myocardium (P<0·05 and 0.01, and P<0·05 and 0.02, respectively) compared to non-failing hearts. Protein abundance of RGS3 and RGS4 was found to be higher in myocardium from end-stage failing hearts, and relative RGS4 expression higher in unused donor hearts.
Conclusions We show here that RGS3 and RGS4 mRNA and protein expression is upregulated in human heart failure. These observations suggest that RGS4 may be induced in the heart to regulate cell signalling pathways in response to hypertrophy, and support the existence of a negative feedback loop for the long-term regulation of hypertrophy.
Key Words: Donor hearts, end-stage heart failure, G-proteins, RGS proteins, mRNA.
f1 Correspondence: Virginia J. Owen, Cardiothoracic Surgery, National Heart and Lung Institute at Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, U.K.
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