A role for Toll-like receptor 3 in lung vascular remodeling associated with SARS-CoV-2 infection
A role for Toll-like receptor 3 in lung vascular remodeling associated with SARS-CoV-2 infection
ABSTRACT Cardiovascular sequelae of severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) disease 2019 (COVID-19) contribute to the complications of the disease. One potential complication is lung vascular remodeling, but the exact cause is still unknown. We hypothesized that endothelial TLR3 insufficiency contributes to lung vascular remodeling induced by SARS-CoV-2. In the lungs of COVID-19 patients and SARS-CoV-2 infected Syrian hamsters, we discovered thickening of the pulmonary artery media and microvascular rarefaction, which were associated with decreased TLR3 expression in lung tissue and pulmonary artery endothelial cells (ECs). In vitro, SARS-CoV-2 infection reduced endothelial TLR3 expression. Following infection with mouse-adapted (MA) SARS-CoV-2, TLR3 knockout mice displayed heightened pulmonary artery remodeling and endothelial apoptosis. Treatment with the TLR3 agonist polyinosinic:polycytidylic acid reduced lung tissue damage, lung vascular remodeling, and endothelial apoptosis associated with MA SARS-CoV-2 infection. In conclusion, repression of endothelial TLR3 is a potential mechanism of SARS-CoV-2 infection associated lung vascular remodeling and enhancing TLR3 signaling is a potential strategy for treatment.
Newcomb Geoffrey、Robinson Richard T.、Farkas Laszlo、Nho Richard、Yount Jacob S.、Goncharova Elena A.、Bogamuwa Srimathi、Elhance Ajit、Horowitz Jeffrey C.、Mejia Oscar Rosas、Piper Bryce、Farkas Daniela、Mallampalli Rama K.、Londino James D.、Gunturu Pranav、Bednash Joseph S.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State UniversityDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State UniversityDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State UniversityDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State UniversityDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State UniversityDivision of Pulmonary, Critical Care & Sleep Medicine, Department of Internal Medicine, University of California DavisDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State UniversityDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State UniversityDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State UniversityDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State UniversityDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State UniversityDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State UniversityDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State UniversityDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State UniversityDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State UniversityDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, Davis Heart & Lung Research Institute, The Ohio State University
基础医学内科学生物科学理论、生物科学方法
Newcomb Geoffrey,Robinson Richard T.,Farkas Laszlo,Nho Richard,Yount Jacob S.,Goncharova Elena A.,Bogamuwa Srimathi,Elhance Ajit,Horowitz Jeffrey C.,Mejia Oscar Rosas,Piper Bryce,Farkas Daniela,Mallampalli Rama K.,Londino James D.,Gunturu Pranav,Bednash Joseph S..A role for Toll-like receptor 3 in lung vascular remodeling associated with SARS-CoV-2 infection[EB/OL].(2025-03-28)[2025-06-29].https://www.biorxiv.org/content/10.1101/2023.01.25.524586.点此复制
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