Deregulation of RGS2 in cardiovascular diseases.
Alteration of G protein-coupled receptor (GPCR) signaling is a salient feature of hypertension and the associated heart diseases. Recent studies have revealed a large family of Regulators of G-protein Signaling (RGS) proteins as important endogenous regulators of GPCR signaling. RGS2 selectively regulates Galphaq/11 signaling, an essential cause of hypertension and cardiac hypertrophy. Both clinical and animal studies have shown that deregulation of RGS2 leads to exacerbated Galphaq/11 signaling. There is an inverse correlation between RGS2 expression and blood pressure, as well as a selective down-regulation of RGS2 in various models of cardiac hypertrophy. The causal relationship has been established in animal studies. RGS2 knockout mice exhibit not only hypertension phenotype but also accelerated cardiac hypertrophy and heart failure in response to pressure-overload. Further in vitro studies have shown that RGS2 knockdown with RNA interference exacerbates, whilst RGS2 over-expression completely abolishes the Galphaq/11-induced hypertrophy. These findings indicate that deregulation of RGS2 plays a crucial role in the pathogenesis of cardiovascular diseases, marking RGS2 as a potential therapeutic target or biomarker of hypertension or hypertensive heart diseases.
Tsang
Sharon
S
Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, MD 21224, USA.
Woo
Anthony Yiu-Ho
AY
Zhu
Weizhong
W
Xiao
Rui-Ping
RP
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000503:physiopathology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D020710:RGS Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D020710:RGS Proteins; C087182:RGS2 protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11