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Neprilysin Inhibitor-Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice #MMPMID31019233
Zhang H; Liu G; Zhou W; Zhang W; Wang K; Zhang J
Sci Rep 2019[Apr]; 9 (1): 6509 PMID31019233show ga
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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Sci+Rep 2019 ; 9 (1): 6509
