SILENCING OF CARDIAC EPIDERMAL GROWTH FACTOR RECEPTOR REDUCES CARDIAC HYPERTROPHY OF ADULT SPONTANEOUSLY HYPERTENSIVE RAT

BREA MS; DIAZ RG; ESCUDERO DS; FUHR J; PORTIANSKY EL; CALDIZ CI; PÉREZ NG

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Epidermal growth factor receptor (EGFR or ErbB1) is an integral membrane protein, that together with other members of the family, ErbB2 and ErbB4 are necessary for a normal adult heart function. EGFR transactivationwas linked to pathological cardiac hypertrophy (PCH). Experimentally, its pharmacological inhibition prevented PCH. The objective of this study was to limit PCH by a specific and localized silencing of cardiac EGFR ofspontaneously hypertensive rats (SHR) with small interference RNA (siRNA). Animals were treated with a sequence that inhibits EGFR expression (l-shEGFR, n=9) or with the non-silencing disordered sequence (l-shSCR,n=10) as control. To promote siRNA entry into the myocardium, it was integrated into the lentivirus genome and injected (1x107 TU / 200 μl) attwo sites of the anterolateral heart wall. After 30 days, animals were sacrificed and hearts removed. Heart left ventricle was weighted (LVW) and normalized to body weight (BW) and tibia length (TL). Morphometric analysis showed that LVW/BW and LVW/TL respectively were reduced in l-shEGFR (2.92 ± 0.05 mg/g and 20.25 ± 0.25 mg/mm) compared to l-shSCR group (3.15 ± 0.08 mg/g and 22.42 ± 0.57 mg/mm; p