Cardiac hypertrophy reduction in SHR by specific silencing of myocardial Na+/H+ exchanger

NOLLY MB; PINILLA OA; ENNIS IL; CINGOLANI HE; MORGAN PE

JOURNAL OF APPLIED PHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Lugar: Bethesda; Año: 2015

8750-7587

We examined the effect of specific and local silencing of sodium hydrogen exchanger 1 (NHE1) with a small hairpin RNA delivered by lentivirus (L-shNHE1) in the cardiac left ventricle (LV) wall of spontaneously hypertensive rats, in order to reduce cardiac hypertrophy. Thirty days after injecting the lentivirus, NHE1 protein expression was reduced 53.3 ± 3 % in the LV of the L-shNHE1 compared to the control group injected with L-shSCR (NHE1 scrambled sequence), without affecting its expression in other organs as liver and lung. Hypertrophic parameters as LV weight (LVW)/body weight and LVW/tibia length were significantly reduced in animals injected with L-shNHE1 (2.32 ± 0.5 and 19.30 ± 0.42 mg/mm, respectively) compared to L-shSCR injected rats (2.68 ± 0.06 and 21.53 ± 0.64 mg/mm, respectively). Hystochemical analysis demonstrated a reduction of cardiomyocytes cross sectional area in animals treated with L-shNHE1 compared to L-shSCR (309,81 ± 20,86 μm2 vs. 424,52 ± 21 μm2, p< 0.05). Echocardiography at the beginning and at the end of the treatment showed that shNHE1 expression for 30 days induced 9 % reduction of LV mass.  Also, animals treated with L-shNHE1 exhibited a reduced LV wall thickness without changing LV diastolic dimension and arterial pressure, indicating an increased parietal stress. In addition, midwall shortening was not modified in spite of the increased wall tension, suggesting an improvement of cardiac function. Chronic shNHE1 expression in the heart emerges as a possible methodology to reduce pathological cardiac hypertrophy, avoiding potentially undesired effects caused from a body-wide inhibition of NHE1.