Cardiac hypertrophy reduction in SHR by specific silencing of myocardial Na(+)/H(+) exchanger
Abstract
We examined the effect of specific and local silencing of sodium/hydrogen exchanger isoform 1 (NHE1) with a small hairpin RNA delivered by lentivirus (L-shNHE1) in the cardiac left ventricle (LV) wall of spontaneously hypertensive rats, to reduce cardiac hypertrophy. Thirty days after the lentivirus was injected, NHE1 protein expression was reduced 53.3 ± 3% in the LV of the L-shNHE1 compared with the control group injected with L-shSCR (NHE1 scrambled sequence), without affecting its expression in other organs, such as liver and lung. Hypertrophic parameters as LV weight-to-body weight and LV weight-to-tibia length ratio were significantly reduced in animals injected with L-shNHE1 (2.32 ± 0.5 and 19.30 ± 0.42 mg/mm, respectively) compared with L-shSCR-injected rats (2.68 ± 0.06 and 21.53 ± 0.64 mg/mm, respectively). Histochemical analysis demonstrated a reduction of cardiomyocytes cross-sectional area in animals treated with L-shNHE1 compared with L-shSCR (309,81 ± 20,86 vs. 424,52 ± 21 μm(2), 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 cha...Continue Reading
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