cAMP Regulated Transcriptional Coactivator 1-A Novel Player in Cardiac Hypertrophy

Maladaptive cardiac hypertrophy leads to heart failure, a common cause for hospitalization. Chronic β-adrenergic, PKA dependent signaling and calcineurin contribute to hypertrophy. These signals converge in many tissues on the cAMP Regulated Transcriptional Coactivator 1 (CRTC1). We studied if CRTC1 promotes the development of maladaptive cardiac hypertrophy in human and murine hearts. In cardiomyocytes, treatment with β-adrenoceptor agonist isoprenaline dephosphorylated, thus activated 59 ± 5 % of total CRTC1, as seen by immunoblot (n = 3-4). Activation was prevented by propranolol. CRTC1 was not activated by endothelin or angiotensin II. CRTC1 protein content was enhanced in human and murine heart tissue under conditions of acquired and inherited maladaptive hypertrophy, seen by immunoblot (n = 7-8). Crtc1-deficient mice (KO) showed a higher ratio of heart weight to tibia length than their wild-type littermates (WT) (8.6 ± 0.4 mg/mm vs. 10.9 ± 0.8 mg/mm in WT and KO, respectively, n = 12) and increased ...