Sacubitril/valsartan inhibits ox‑LDL‑induced MALAT1 expression, inflammation and apoptosis by suppressing the TLR4/NF‑κB signaling pathway in HUVECs

The therapeutic effect of sacubitril/valsartan (S/V) on heart failure has been confirmed, while its role in atherosclerosis remains largely unexplored. The present study aimed to investigate the effects of S/V on the expression of metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1), inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) induced by oxidized low‑density lipoprotein (ox‑LDL) and to elucidate its possible mechanism. Cell Counting Kit‑8 assay was used to detect cell viability. Reverse transcription‑quantitative PCR was performed to detect the MALAT1 expression. ELISA was performed to detect the levels of IL‑1β, IL‑6 and TNF‑α. Flow cytometry was conducted to detect the apoptotic rate of cells. A nitric oxide (NO) detection kit was used to determine the concentration of NO. Western blotting analysis was performed to determine the levels of intercellular cell adhesion molecule (ICAM)‑1, vascular cell adhesion molecule (VCAM)‑1, endothelin‑1, caspase‑3, Bax, Bcl‑2, Toll‑like receptor 4 (TLR4), p65 and p‑p65. Compared with the ox‑LDL group, S/V treatment significantly increased the cell viability, NO concentration and Bcl‑2 expression, decreased the levels of IL‑1β, IL‑6 and TNF‑α and reduced the expressions of MALAT1, ICAM‑1, VCAM‑1, cleaved‑caspase‑3, Bax, TLR4 and p‑p65. Overall, the findings suggested that S/V could downregulate the expression of MALAT1, inhibit inflammation and apoptosis and improve endothelial function in ox‑LDL‑induced HUVECs via inactivating the TLR4/NF‑κB signaling pathway. Therefore, S/V might be utilized as a promising therapeutic strategy for the prevention and treatment of atherosclerosis.