Abstract 419: Investigating the Role of Epidermal Growth Factor Receptors in Angiotensin II-induced Hypertrophic Signalling in Cardiomyocytes [Poster Session II]

Cardiac hypertrophy is characterized by stimulation of hypertrophic signalling pathways representing the reactivation of the ‘foetal gene program’ (hypertrophic genes) and activation of the MAPK pathway. Angiotensin II (AngII) stimulates cardiac hypertrophy, a process which may involve the transactivation of epidermal growth factor receptors (ErbBs). Three subtypes of ErbBs are present in the postnatal heart (ErbB1, 2, 4), yet their precise roles are poorly understood. We have shown that the ErbB4-selective ligand neuregulin 1 beta-1 (NRG1-β1) potently stimulates cardiomyocyte hypertrophy. We now aim to determine if AngII activates hypertrophic signalling in cardiomyocytes by transactivation of ErbBs, particularly ErbB4.Ventricular cardiomyocytes from neonatal rats were treated with AngII (100 nM) or NRG1-β1 (10 nM) to induce hypertrophic signalling. ErbB1, 2, 4 were downregulated using shRNA and siRNA. Reporter assays were used to measure promoter activity of the hypertrophic genes myosin light chain 2v (MLC-2V), atrial natriuretic peptide (ANP) and cyclin D. ERK1/2 activation was measured via Western blot.NRG caused robust activation of the hypertrophic gene MLC-2V (11.3 fold increase versus untreated control) that was significantly reduced to 4.3-fold by silencing of ErbB4 (n = 5, P < 0.01), but not ErbB1 or ErbB2, confirming that ErbB4 activation contributes to hypertrophic signalling. However, knockdown of ErbB1, 2 or 4 did not affect AngII-induc...
Source: Hypertension - Category: Cardiology Authors: Tags: Poster Session II Source Type: research