Kaempferol alleviates ox-LDL-induced apoptosis by up-regulation of miR-26a-5p via inhibiting TLR4/NF-κB pathway in human endothelial cells

Background: Oxidized low-density lipoprotein (ox-LDL) has been well-documented to induce endothelial cell (EC) apoptosis and contribute to the progression of atherosclerosis. Kaempferol was reported to alleviate ox-LDL-induced apoptosis of human umbilical vein endothelial cells. However, the detailed mechanism by which kaempferol alleviated ox-LDL-induced EC apoptosis remains largely elusive. Methods: The expression of miR-26a-5p in human aortic endothelial cells (HAECs) treated with either ox-LDL alone or in combination with kaempferol was detected by qRT-PCR. Cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. The interaction between miR-26a-5p and toll-like receptor 4 (TLR4) mRNA was examined by luciferase reporter assay. The protein levels of TLR4, phosphorylated-p65, p65, phosphorylated-I kappa B alpha and I kappa B alpha were determined by western blot. Results: Kaempferol upregulated miR-26a-5p expression in ox-LDL-stimulated HAECs. Moreover, kaempferol alleviated ox-LDL-induced apoptosis in HAECs by upregulating miR-26a-5p. Additionally, TLR4 mRNA was identified as a target of miR-26a-5p in ox-LDL-treated HAECs. TLR4 overexpression partially counteracted the anti-apoptotic role of miR-26a-5p in ox-LDL-treated HAECs. Furthermore, kaempferol inactivated the TLR4/nuclear factor kappa B (NF-kappa B) signaling pathway in ox-LDL-treated HAECs by upregulating miR-26a-5p. Conclusion: Kaempferol alleviated ox-LDL-induced apoptosis in HAECs by upregulating miR-26a-5p via inactivation of the TLR4/NF-kappa B signaling pathway, shedding light on the molecular mechanism by which kaempferol alleviated ox-LDL-induced EC apoptosis.