Effect of cardiac EGFR silencing with siRNA on the slow force response to myocardial stretch

BREA MS, DÍAZ RG, ESCUDERO DS, LEPORACE GUIMIL J, CALDIZ CI, PÉREZ NG, MORGAN PE

Rosario

Congreso; L Reunión de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB) 2014; 2014

The stretch of cardiac muscle produces an initial fast increase in force, followed by a slow force response (SFR). The SFR seems to be due to an autocrine mechanism that involves the activation of the epidermal growth factor receptor (EGFR) and the consequent generation and release of reactive oxygen species (ROS). We developed a lentivirus carrying shEGFR sequence to inhibit EGFR expression, without affecting cardiac family members ErbB2 and ErbB4, and injected into a rat cardiac left ventricular wall (n=5). As control, a second group of sham rats were injected with phosphate buffer saline (PBS, n=5). Four-week later, EGFR protein expression in the left ventricle of shEGFR expressing rats showed 52 ± 15 % reduction compared to sham animals (100 ± 6 %, P<0.05). The SFR, evaluated in isolated left ventricle papillary muscles, was blunted in animals expressing shEGFR (in % of initial phase: 102 ± 1 vs. sham 112 ± 1, P<0.05). ROS production (evaluated by the lucigenin method) was assessed in cardiac left ventricle stripes after AII (1 nM) and EGF (0.1 mg/ml) stimulation. AII and EGF increased basal ROS production in sham rats by 47 ± 2 and 43 ± 6 % respectively, effect that was significantly reduced in shEGFR expressing rats (5 ± 5 and 17 ± 12 % respectively). We conclude that EGFR activation is crucial for the redox-sensitive mechanism that triggers the SFR to myocardial stretch.