Key result
Sacubitril/valsartan (LCZ696) significantly suppressed atherosclerotic plaque formation and inhibited pro-inflammatory gene expression in apoE-deficient mice more effectively than valsartan alone.
Why the study?
The effects of sacubitril/valsartan combination drug (LCZ696) compared to valsartan alone on atherosclerotic plaque progression and inflammatory gene expression required assessment.
Does sacubitril/valsartan reduce atherosclerotic plaque formation and inflammation in apolipoprotein E-deficient mice compared to valsartan alone?
Does sacubitril/valsartan reduce atherosclerotic plaque formation and inflammation in apolipoprotein E-deficient mice compared to valsartan alone?
p-value: p=<0.05
Sacubitril/valsartan (LCZ696) suppresses atherosclerotic plaque formation and systemic inflammation more effectively than valsartan alone in an apoE-/- mouse model.
LCZ696 outperformed valsartan in reducing plaque and inflammation in apoE−/− mice; leaves open clinical translation to humans.
We assessed the effects of the sacubitril/valsartan combination drug (LCZ696), in comparison to valsartan alone, on the progression of atherosclerotic plaque formation and inflammatory gene expression in apolipoprotein E- deficient mice (apoE −/− mice). Seventy-two apoE −/− mice were fed a western diet and a constrictive silastic tube was used to elicit carotid lesion formation. The animals were separated into a control group, a valsartan group or an LCZ696 group (n = 24 in each group). Plaques in the carotid artery were harvested 12 weeks later for histological examination. The levels of pro-inflammatory genes in the plasma and lesions were detected using real-time PCR and ELISA. Valsartan or LCZ696 treatment remarkably inhibited the expression of pro-inflammatory genes, including interleukin-6, matrix metalloproteinase-8 and monocyte chemotactic protein-1, in comparison with the control group. Meanwhile, both valsartan and LCZ696 suppressed the formation of atherosclerotic plaques by decreasing plaque lipid content and cross-sectional plaque area and increasing the content of plaque collagen and fibrous cap thickness. In particular, LCZ696 performed the best in suppressing atherosclerosis and inhibiting the level of pro-inflammatory genes. LCZ696 significantly ameliorated atherosclerosis and inflammation in apoE −/− mice compared with valsartan.
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Zhang et al. (2019) studied Atherosclerosis (n=72). Sacubitril/valsartan (LCZ696) vs. Valsartan (3 mg/kg/day) or Control (corn oil) was evaluated on Atherosclerotic plaque formation (plaque area, lipid content, collagen content, fibrous cap thickness) and inflammatory gene expression (p=<0.05). Sacubitril/valsartan (LCZ696) significantly suppressed atherosclerotic plaque formation and inhibited pro-inflammatory gene expression in apoE-deficient mice more effectively than valsartan alone.
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