Silencing of the epidermal growth factor receptor (EGFR) blunts the slow force response to myocardial stretch.

BREA MS; DIAZ RG; MORGAN PE; CALDIZ CI; PÉREZ NG

Buenos Aires

Congreso; ISHR XXII World Congress; 2016

International Society of Heart Research

Myocardial stretch induces a biphasic force increase: A first phase due to the Frank-Starling mechanism, followed by a slower one called slow force response (SFR). The SFR is due to a complex autocrine mechanism that appears to involve Angiotensin II (AII)-triggered EGFR transactivation and the consequent generation/release of reactive oxygen species (ROS) leading to Na+/H+ exchanger (NHE1) activation. In order to conclusively prove the role of the EGFR in the SFR, we developed a lentivirus carrying a siRNA against EGFR (siEGFR), and injected it into the rat cardiac left ventricular wall (n=8). A scramble (SCR) sequence was used as control (n=9). After 4 weeks, EGFR protein expression showed a 48±15% reduction in siEGFR-injected hearts compared to SCR (100±6%, p