Inhibition Effect of TLR4mAb on mmLDL Impaired Endothelium-dependent Vasodilatation in Mouse Mesenteric Artery / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effect and mechanism of TLR4 monoclonal antibody (TLR4mAb) on mmLDL induced impairment of endothelium-dependent vasodilatation in mouse mesenteric artery. METHODS: The experiment established three groups of normal saline group, mmLDL treatment group and TLR4mAb intervention group. The concentration of IL-1β and TNF-α in plasma was determined by enzyme-linked immunosorbent assay (ELISA). Measurement of endothelium-dependent vasodilatation was achieved by microvascular tension mapping. Western blot and RT-PCR were used to investigate the expression level of protein and mRNA expressions in vascular tissues. In addition, ultra-structure of mesenteric artery endothelial cells was observed by transmission electron microscope. RESULTS: TLR4mAb could improve the damage of mmLDL induced impairment of endothelium-dependent vasodilatation in a dose-dependent manner. Besides, TLR4mAb obviously up-regulated protein expressions in KCa3.1-channel and KCa2.3-channel, and down-regulated the expression of inflammatory factors TNF-α and IL-1β. Furthermore, the improvement of mmLDL impaired vascular endothelial cells and endothelium-dependent vasodilatation might be correlated with its competitive antagonism of mmLDL-activated TLR4 signal transduction pathway and its downstream NF-κBp65 and p-38 MAPK pathway. CONCLUSION: Administration of TLR4mAb in advance can alleviate the impairment of endothelial cells and the decrease of endothelium-dependent vasodilatation induced by mmLDL, and inhibit the overexpression of inflammatory factors. Regulation of TLR4 pathway as well as its downstream NF-κBp65 and P-38 MAPK pathways may be effective targets for the prevention and treatment of cardiovascular diseases.