Affiliation:
1. Department of Cardiology Shanghai Eighth People's Hospital Shanghai China
Abstract
AbstractBackgroundOxidized forms of low‐density lipoproteins (ox‐LDL)‐associated endothelial dysfunction and subsequent monocyte adhesion play an important role in the development of atherosclerosis (AS). Bezafibrate (BEZ) is a peroxisome proliferator‐activated receptor (pan‐PPAR) agonist licensed as a hypolipidemic drug. However, the effects of BEZ on endothelial dysfunction are less reported.ObjectivesIn this study, we aim to investigate the protective effects of BEZ on ox‐LDL‐challenged vascular endothelial cells to evaluate its potential value in treating AS.MethodsHuman aortic endothelial cells (HAECs) and THP‐1 cells were used to establish an In Vitro AS model. Cell Counting Kit‐8 (CCK‐8) assay, Real‐time PCR, Western blot analysis, and Enzyme‐linked immunosorbent assay (ELISA) were used to test the data.ResultsAs expected, treatment with BEZ suppressed the expression of vascular endothelial growth factor A (VEGF‐A), tissue factor (TF), Interleukin 12 (IL‐12), tumor necrosis factor (TNF‐α), and monocyte chemoattractant protein‐1 (MCP‐1). BEZ was also found to inhibit ox‐LDL‐induced expression of the endothelial adhesion molecules vascular cellular adhesion molecule‐1 (VCAM‐1) and intercellular adhesion molecule‐1 (ICAM‐1) in HAECs. Correspondingly, BEZ prevented attachment of THP‐1 monocytes to ox‐LDL‐incubated HAECs. Mechanically, BEZ was found to prevent NF‐κB activation by reducing the levels of nuclear NF‐κB p65 and inhibiting luciferase activity of NF‐κB.ConclusionOur study revealed the pharmacological function of BEZ in protecting endothelial dysfunction against ox‐LDL, which may provide valuable insight for the clinical application of BEZ.