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

BREA MS; DÍAZ RG; ESCUDERO DS; FUHR J; PORTIANSKY EL; CALDIZ CI ; PÉREZ NG; MORGAN PE

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

               Epidermal growth factorreceptor (EGFR or ErbB1) is an integral membrane protein, that together withother members of the family, ErbB2 and ErbB4 are necessary for a normal adultheart function. EGFR transactivation was linked to pathological cardiachypertrophy (PCH). Experimentally, its pharmacological inhibition prevented PCH.The objective of this study was to limit PCH by a specific and localizedsilencing of cardiac EGFR of spontaneously hypertensive rats (SHR) with smallinterference RNA (siRNA). Animals were treated with a sequence that inhibitsEGFR 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 wasintegrated into the lentivirus genome and injected (1x107TU / 200 μl) at two sites of the anterolateral heart wall.After 30 days, animals were sacrificed and hearts removed. Heart left ventriclewas weighted (LVW) and normalized to body weight (BW) and tibia length (TL).Morphometric analysis showed that LVW/BW and LVW/TL respectively were reducedin 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<0.05). This reduction wasaccompanied by a decrease of ​​themyocytes cross sectional area: 246.3 ± 20.6 mm2 l-shEGFR vs. 298.3 ± 9.8 mm2 l-shSCR, (p<0.05), evaluated by hematoxylosin-eosinstaining of LV histological sections. Since EGFR inhibition could reduceredox-sensitive pathways, myocardial lipid peroxidation (by thiobarbituricreactive substances, TBARS) and basal reactive oxygen species (ROS) wereevaluated in both experimental groups. Both TBARS and ROS were reduced in LVmyocardium of SHR injected with l-shEGFR vs. l-shSCR (p<0.05). These resultsdemonstrate that 1) normal EGFR expression is necessary to mediate cardiachypertrophy, 2) suggest specific silencing of EGFR in the myocardium as analternative therapeutic strategy for PCH treatment.