The therapeutic potential of targeting cardiac RGS4

Figures

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  Figure 1.. Role of cardiomyocyte RGS4 in the context of human HF. Basal and hormone induced (e.g. by adenosine A1 and A3 or M2 muscarinic cholinergic receptors) Gαi activity is elevated, so cAMP levels are low in human HF. RGS4, by accelerating GTP hydrolysis on Gαi, functionally opposes/terminates Gαi actions, thereby (indirectly) promoting AC activation and cAMP synthesis. cAMP exerts multiple effects in the heart crucial for cardiomyocyte function, such as contraction followed by relaxation, automaticity, and positive chronotropy and dromotropy (conduction). Thus, RGS4 can potentially reverse part of the molecular abnormalities present in the failing human myocardium. A, adenine; AC, adenylyl cyclase; ATP, adenosine triphosphate; cAMP, 3′,5′-adenosine monophosphate; G, guanine; HF, heart failure; P, phosphorylation; Pi, inorganic phosphate; RGS, regulator of G protein signaling. See text for more details and all other molecular acronym descriptions.

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  Figure 2.. Role of (atrial) cardiomyocyte RGS4 in the context of human AFib. RGS4 terminates Gq protein signaling induced by AngII and ET-1 receptors, thereby attenuating pro-arrhythmic calcium signaling and reducing risk of AFib development. ACh, acetylcholine; AFib, atrial fibrillation; AngII, angiotensin II; ET-1, endothelin-1; HR, heart rate; IP3, inositol 1′,4′,5′-trisphosphate; RGS, regulator of G protein signaling. See text for more details and all other molecular acronym descriptions.