Azilsartan ameliorates ox-LDL-induced endothelial dysfunction via promoting the expression of KLF2
| Autor: | Chenggao Wang, Dandan Zhang, Wenfeng Li, Jun Luo, Feng Chen, Shihui Xiao, Kanghua Zeng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Aging
Chemokine Small interfering RNA Azilsartan Drug Evaluation Preclinical Kruppel-Like Transcription Factors ox-LDL Pharmacology Occludin endothelial dysfunction Enos medicine Human Umbilical Vein Endothelial Cells Humans Endothelial dysfunction Oxadiazoles biology Chemistry Cell Biology medicine.disease biology.organism_classification Atherosclerosis CXCL1 Endothelial stem cell Lipoproteins LDL Gene Expression Regulation Gene Knockdown Techniques biology.protein Benzimidazoles Endothelium Vascular medicine.drug Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|