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Toll-like receptor protein 4 monoclonal antibody inhibits mmLDL-induced endothelium-dependent vasodilation dysfunction of mouse mesenteric arteries.

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机构: [1]The First People's Hospital of Chenzhou, Xiangnan University, Chenzhou, Hu'nan, China [2] Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hu'nan, China [3]Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China [4] Department of Pharmacy, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
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关键词: TLR4 mAb mmLDL Inflammation Mesenteric artery Endothelium-dependent vasodilation

摘要:
Minimally modified low-density lipoprotein (mmLDL) is a risk factor for cardiovascular disease. This study was designed to investigate the effect of a Toll-like receptor 4 monoclonal antibody (TLR4 mAb) on mmLDL-induced endothelium-dependent vasodilation (EDV) impairment in mouse mesenteric arteries and to explore the underlying mechanism. Animals were divided into a normal control group, an mmLDL treatment group, and a TLR4 mAb intervention group. The serum concentrations of IL-1β and TNF-α were detected using enzyme-linked immunosorbent assays (ELISAs). EDV function was measured using a microvascular tension tracing method. The protein levels and mRNA expression of IL-1β and TNF-α in vascular tissue were detected using western blot analysis and reverse transcription polymerase chain reaction, respectively. TLR4 mAb improved mmLDL-induced EDV functional impairment in a dose-dependent manner. TLR4 mAb significantly upregulated KCa3.1 and KCa2.3 channel protein levels and downregulated TNF-α and IL-1β expression. These effects were possibly associated with the competitive antagonism of TLR4 mAb on the TLR4 signaling pathway and the downstream NF-κB p65 and p38 MAPK pathways, which are activated by mmLDL. In conclusion, pretreatment with TLR4 mAb lessens mmLDL-induced EDV dysfunction and inhibits overexpression of inflammatory factors. Regulation of the TLR4 pathway, as well as its downstream NF-κB p65 and p38 MAPK pathways, may be an effective strategy for the prevention and treatment of cardiovascular diseases. Copyright © 2019 Elsevier Inc. All rights reserved.

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出版当年[2020]版:
大类 | 3 区 医学
小类 | 3 区 外周血管病
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 外周血管病
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第一作者机构: [2] Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hu'nan, China
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通讯机构: [1]The First People's Hospital of Chenzhou, Xiangnan University, Chenzhou, Hu'nan, China [2] Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hu'nan, China [*1]The First People's Hospital of Chenzhou, Xiangnan University, Chenzhou, Hu'nan 423000, China.
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