Cardiac natriuretic peptides inhibit TRPC6-mediated prohypertrophic signaling through cGMP-PKG pathway

Cardiac natriuretic peptides, atrial and brain natriureticpeptides (ANP and BNP, respectively) are known to haveanti-cardiac hypertrophy effects. ANP and BNP bind totheir common receptor, guanylyl cyclase-A, which subse-quently activates cGMP-protein kinase G (PKG) pathway.Precise molecular mechanisms by which cardiac natriu-retic peptides protect hearts against pathological cardiachypertrophy still remain unclear, however. Transientreceptor potential (TRP) C6, an ion channel responsiblefor the receptor-activated Ca2+ entry, has been shown tobe a positive regulator of calcineurin-NFAT signalingpathway that drives pathologic cardiac remodeling [1]. Inthis study to elucidate the molecular pathways, by whichcardiac natriuretic peptides negatively regulate pro-hyper-trophic signaling, we investigated effects of ANP onTRPC6-calcineurin-NFAT signaling.