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Background Oxidized LDL(Ox-LDL) mediated endothelial dysfunction is involved in the pathogenesis of various cardiovascular diseases, including atherosclerosis. Azilsartan is a potent agent for the treatment of hypertension as the antagonist of the angiotensin II receptor. This study will investigate whether Azilsartan possesses a beneficial effect against endothelial cell dysfunction induced by ox-LDL and explore the underlying preliminary mechanism. Methods Ox-LDL was applied to construct an in vitro endothelial dysfunction model in human umbilical vascular endothelial cells (HUVECs). The expression of lectin-type oxidized LDL receptor 1 (LOX-1), endothelial nitric oxide synthase (eNOS), tight junction protein occludin, and transcriptional factor Kruppel-like factor 2 (KLF2) was detected using qRT-PCR and Western blot. ELISA and qRT-PCR were utilized to evaluate the production of chemokine monocyte chemotactic protein 1 (MCP-1) and chemokine (C-X-C motif) Ligand 1 Protein (CXCL1) in treated HUVECs. The generation of nitro oxide (NO) was determined using DAF-FM DA staining assay. KLF2 was silenced by transfecting the cells with specific Small interfering RNA (siRNA). FITC-dextran permeation assay was used to check the endothelial monolayer permeability of treated HUVECs. Results Firstly, the elevated expressions of LOX-1, MCP-1, and CXCL-1 induced by stimulation with ox-LDL were significantly suppressed by Azilsartan. The downregulated eNOS and reduced production of NO induced by ox-LDL were reversed by the introduction of Azilsartan. Secondly, enlarged endothelial monolayer permeability and decreased expression of occludin stimulated with ox-LDL were greatly reversed by treatment with Azilsartan but were abolished by silencing the expression of KLF2. Lastly, the inhibited expression of KLF2 induced by ox-LDL was significantly elevated by the introduction of Azilsartan. Conclusion Azilsartan might ameliorate ox-LDL-induced endothelial damage via elevating the expression of KLF2.

Cardiovascular disease (CVD) has been considered as a major risk factor of death in recent decades. In CVDs, the NLRP3 inflammasome is important for inflammatory response and vascular damage. Therefore, safe and effective treatments to decrease NLRP3 inflammasome activation are required. Increased levels of free fatty acid (FFA) have been associated with the progression of CVD. Humanin, a kind of mitochondrial-derived peptide, has shown its beneficial effects in different types of cells. However, the roles of humanin in the NLRP3 inflammasome induced by FFA are still unknown. Here, we investigated the molecular mechanisms whereby humanin was found to exert protective effects in human aortic endothelial cells (HAECs) against FFA-caused endothelial injury. Here, treatment with humanin inhibited FFA-induced lactate dehydrogenase release, thereby demonstrating a protective capacity against cell death. Humanin also suppressed oxidative stress by downregulating the expression of reactive oxygen species and NOX2. Notably, humanin reduced NLRP3 and p10 and rescued FFA-induced dysfunction of adenosine monophosphate-activated protein kinase. Consequently, humanin inhibited the expression of IL-1β and IL-18. These results conclude that humanin might be a promising therapeutic agent for CVD.