Expression of RGS3, RGS4 and Gi alpha 2 in acutely failing donor hearts and end-stage heart failure

Background Regulators of G-protein Signalling (RGS) proteins have been show n to limit in vitro signalling of G proteins. In common with end-stage hear t failure, we have recently shown that upregulation of the inhibitory G-pro tein, Gia, occurs in acutely failing donor hearts unused for transplantatio n due to severe myocardial dysfunction, In light of recent data on RGS prot eins, we have evaluated mRNA and protein expression of RGS3, RGS4 and Gia2 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 wi th ejection fractions < 30% (n=14) and used donor hearts with good function (ejection fraction > 60%) (n=4.7). mRNA levels were quantified using quant itative reverse transcriptase polymerase chain reaction. Levels of RGS3 and RGS4 mRNA were found to be significantly Upregulated in unused donor and e nd-stage failing myocardium (P <0.05 and 0.01, and P <0.05 and 0.02, respec tively) compared to non-failing hearts. Protein abundance of RGS3 and RGS4 was found to be higher in myocardium from end-stage failing hearts, and rel ative 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 ma y be induced in the heart to regulate cell signalling pathways in response to hypertrophy, and support the existence of a negative feedback loop for t he long-term regulation of hypertrophy. (C) 2001 The European Society of Ca rdiology.