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

BREA MS; JOSEFINA FUHR; PEREZ, NESTOR GUSTAVO; DIAZ, ROMINA GISEL; PORTIANSKY EL; DAIANA S. ESCUDERO; CALDIZ CI

Buenos Aires

Congreso; Reunion Conjunta de Sociedades de Biociencia; 2017

Sociedades Argentinas de Biociencias (en conjunto)

Epidermal growth factor receptor (EGFR or ErbB1) isan integral membrane protein, that together with othermembers of the family, ErbB2 and ErbB4 are necessaryfor a normal adult heart function. EGFR transactivationwas linked to pathological cardiac hypertrophy (PCH).Experimentally, its pharmacological inhibition preventedPCH. The objective of this study was to limit PCHby a specific and localized silencing of cardiac EGFR ofspontaneously hypertensive rats (SHR) with small interferenceRNA (siRNA). Animals were treated with a sequencethat 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 andinjected (1x107 TU / 200 μl) attwo sites of the anterolateralheart wall. After 30 days, animals were sacrificedand hearts removed. Heart left ventricle was weighted(LVW) and normalized to body weight (BW) and tibialength (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 tol-shSCR group (3.15 ± 0.08 mg/g and 22.42 ± 0.57 mg/mm; p