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Blockage of C-X-C Motif Chemokine Receptor 2 (CXCR2) Suppressed Uric Acid (UA)-Induced Cardiac Remodeling

Hyperuricemia-induced cardiac remodeling is at least in part via pressure-dependent mechanisms, yet the pressure-independent mechanisms are not well understood. C-X-C motif chemokine ligand 1 (CXCL1) was upregulated in renal tubules from mice subjected to uric acid (UA)-induced nephropathy. Given th...

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Autores principales: Xu, Mingxi, Zheng, Xu, Wang, Dongxia, Fu, Xiaodan, Xing, Yida, Liu, Yu, Wang, Hongjiang, Kong, Xiaodan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353369/
https://www.ncbi.nlm.nih.gov/pubmed/34385934
http://dx.doi.org/10.3389/fphys.2021.700338
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author Xu, Mingxi
Zheng, Xu
Wang, Dongxia
Fu, Xiaodan
Xing, Yida
Liu, Yu
Wang, Hongjiang
Kong, Xiaodan
author_facet Xu, Mingxi
Zheng, Xu
Wang, Dongxia
Fu, Xiaodan
Xing, Yida
Liu, Yu
Wang, Hongjiang
Kong, Xiaodan
author_sort Xu, Mingxi
collection PubMed
description Hyperuricemia-induced cardiac remodeling is at least in part via pressure-dependent mechanisms, yet the pressure-independent mechanisms are not well understood. C-X-C motif chemokine ligand 1 (CXCL1) was upregulated in renal tubules from mice subjected to uric acid (UA)-induced nephropathy. Given that CXCL1 is a master chemokine responsible for the recruitment of macrophage by binding with its receptor C-X-C motif chemokine receptor 2 (CXCR2), we thus hypothesized that UA-induced cardiac injury is via promoting the recruitment of CXCR2 + macrophages into the heart, which enhances cardiac inflammation. Within a mouse model of UA injection (500 mg/kg, twice/day, 14 days), we measured the level of cardiac CXCL1. We also tested the efficacy of the CXCR2 antagonist on UA-induced cardiac inflammation and remodeling. We found a high plasma level of UA-induced upregulation of CXCL1 in heart tissues. CXCR2 antagonist relieved UA-induced cardiac hypertrophy and suppressed cardiac inflammation and fibrosis. The silencing of CXCR2 in human monocytes abolished the migration of UA-induced monocyte. Thus, the interventions against CXCL1/CXCR2 may be effective for the prevention and treatment of UA-induced cardiac hypertrophy and inflammatory responses.
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spelling pubmed-83533692021-08-11 Blockage of C-X-C Motif Chemokine Receptor 2 (CXCR2) Suppressed Uric Acid (UA)-Induced Cardiac Remodeling Xu, Mingxi Zheng, Xu Wang, Dongxia Fu, Xiaodan Xing, Yida Liu, Yu Wang, Hongjiang Kong, Xiaodan Front Physiol Physiology Hyperuricemia-induced cardiac remodeling is at least in part via pressure-dependent mechanisms, yet the pressure-independent mechanisms are not well understood. C-X-C motif chemokine ligand 1 (CXCL1) was upregulated in renal tubules from mice subjected to uric acid (UA)-induced nephropathy. Given that CXCL1 is a master chemokine responsible for the recruitment of macrophage by binding with its receptor C-X-C motif chemokine receptor 2 (CXCR2), we thus hypothesized that UA-induced cardiac injury is via promoting the recruitment of CXCR2 + macrophages into the heart, which enhances cardiac inflammation. Within a mouse model of UA injection (500 mg/kg, twice/day, 14 days), we measured the level of cardiac CXCL1. We also tested the efficacy of the CXCR2 antagonist on UA-induced cardiac inflammation and remodeling. We found a high plasma level of UA-induced upregulation of CXCL1 in heart tissues. CXCR2 antagonist relieved UA-induced cardiac hypertrophy and suppressed cardiac inflammation and fibrosis. The silencing of CXCR2 in human monocytes abolished the migration of UA-induced monocyte. Thus, the interventions against CXCL1/CXCR2 may be effective for the prevention and treatment of UA-induced cardiac hypertrophy and inflammatory responses. Frontiers Media S.A. 2021-07-27 /pmc/articles/PMC8353369/ /pubmed/34385934 http://dx.doi.org/10.3389/fphys.2021.700338 Text en Copyright © 2021 Xu, Zheng, Wang, Fu, Xing, Liu, Wang and Kong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Xu, Mingxi
Zheng, Xu
Wang, Dongxia
Fu, Xiaodan
Xing, Yida
Liu, Yu
Wang, Hongjiang
Kong, Xiaodan
Blockage of C-X-C Motif Chemokine Receptor 2 (CXCR2) Suppressed Uric Acid (UA)-Induced Cardiac Remodeling
title Blockage of C-X-C Motif Chemokine Receptor 2 (CXCR2) Suppressed Uric Acid (UA)-Induced Cardiac Remodeling
title_full Blockage of C-X-C Motif Chemokine Receptor 2 (CXCR2) Suppressed Uric Acid (UA)-Induced Cardiac Remodeling
title_fullStr Blockage of C-X-C Motif Chemokine Receptor 2 (CXCR2) Suppressed Uric Acid (UA)-Induced Cardiac Remodeling
title_full_unstemmed Blockage of C-X-C Motif Chemokine Receptor 2 (CXCR2) Suppressed Uric Acid (UA)-Induced Cardiac Remodeling
title_short Blockage of C-X-C Motif Chemokine Receptor 2 (CXCR2) Suppressed Uric Acid (UA)-Induced Cardiac Remodeling
title_sort blockage of c-x-c motif chemokine receptor 2 (cxcr2) suppressed uric acid (ua)-induced cardiac remodeling
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353369/
https://www.ncbi.nlm.nih.gov/pubmed/34385934
http://dx.doi.org/10.3389/fphys.2021.700338
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