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Blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding macrophage infiltration

Cardiac remodeling is an important mechanism of heart failure, which frequently results from leukocyte infiltration. Vascular cellular adhesion molecule-1 (VCAM-1) plays a critical role in leukocyte adhesion and transmigration. However, the importance of VCAM-1 in the development of angiotensin II (...

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Autores principales: Qiu, Ze-Yang, Yu, Wei-Jia, Bai, Jie, Lin, Qiu-Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713306/
https://www.ncbi.nlm.nih.gov/pubmed/36467095
http://dx.doi.org/10.3389/fphar.2022.1058268
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author Qiu, Ze-Yang
Yu, Wei-Jia
Bai, Jie
Lin, Qiu-Yue
author_facet Qiu, Ze-Yang
Yu, Wei-Jia
Bai, Jie
Lin, Qiu-Yue
author_sort Qiu, Ze-Yang
collection PubMed
description Cardiac remodeling is an important mechanism of heart failure, which frequently results from leukocyte infiltration. Vascular cellular adhesion molecule-1 (VCAM-1) plays a critical role in leukocyte adhesion and transmigration. However, the importance of VCAM-1 in the development of angiotensin II (Ang II)-induced cardiac remodeling remains unclear. Wild-type (WT) mice were infused with Ang II (1,000 ng/kg/min) for 14 days and simultaneously treated with VCAM-1 neutralizing antibody (0.1 or 0.2 mg) or IgG control. Systolic blood pressure (SBP) and cardiac function were detected by a tail-cuff and echocardiography. Cardiac remodeling was evaluated by histological staining. Adhesion and migration of bone marrow macrophages (BMMs) were evaluated in vitro. Our results indicated that VCAM-1 levels were increased in the serum of patients with heart failure (HF) and the hearts of Ang II-infused mice. Furthermore, Ang II-caused hypertension, cardiac dysfunction, hypertrophy, fibrosis, infiltration of VLA-4+ BMMs and oxidative stress were dose-dependently attenuated in mice administered VCAM-1 neutralizing antibody. In addition, blocking VCAM-1 markedly alleviated Ang II-induced BMMs adhesion and migration, therefore inhibited cardiomyocyte hypertrophy and fibroblast activation. In conclusion, the data reveal that blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding VLA-4+ macrophage infiltration. Selective blockage of VCAM-1 may be a novel therapeutic strategy for hypertensive cardiac diseases.
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spelling pubmed-97133062022-12-02 Blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding macrophage infiltration Qiu, Ze-Yang Yu, Wei-Jia Bai, Jie Lin, Qiu-Yue Front Pharmacol Pharmacology Cardiac remodeling is an important mechanism of heart failure, which frequently results from leukocyte infiltration. Vascular cellular adhesion molecule-1 (VCAM-1) plays a critical role in leukocyte adhesion and transmigration. However, the importance of VCAM-1 in the development of angiotensin II (Ang II)-induced cardiac remodeling remains unclear. Wild-type (WT) mice were infused with Ang II (1,000 ng/kg/min) for 14 days and simultaneously treated with VCAM-1 neutralizing antibody (0.1 or 0.2 mg) or IgG control. Systolic blood pressure (SBP) and cardiac function were detected by a tail-cuff and echocardiography. Cardiac remodeling was evaluated by histological staining. Adhesion and migration of bone marrow macrophages (BMMs) were evaluated in vitro. Our results indicated that VCAM-1 levels were increased in the serum of patients with heart failure (HF) and the hearts of Ang II-infused mice. Furthermore, Ang II-caused hypertension, cardiac dysfunction, hypertrophy, fibrosis, infiltration of VLA-4+ BMMs and oxidative stress were dose-dependently attenuated in mice administered VCAM-1 neutralizing antibody. In addition, blocking VCAM-1 markedly alleviated Ang II-induced BMMs adhesion and migration, therefore inhibited cardiomyocyte hypertrophy and fibroblast activation. In conclusion, the data reveal that blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding VLA-4+ macrophage infiltration. Selective blockage of VCAM-1 may be a novel therapeutic strategy for hypertensive cardiac diseases. Frontiers Media S.A. 2022-11-17 /pmc/articles/PMC9713306/ /pubmed/36467095 http://dx.doi.org/10.3389/fphar.2022.1058268 Text en Copyright © 2022 Qiu, Yu, Bai and Lin. 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 Pharmacology
Qiu, Ze-Yang
Yu, Wei-Jia
Bai, Jie
Lin, Qiu-Yue
Blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding macrophage infiltration
title Blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding macrophage infiltration
title_full Blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding macrophage infiltration
title_fullStr Blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding macrophage infiltration
title_full_unstemmed Blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding macrophage infiltration
title_short Blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding macrophage infiltration
title_sort blocking vcam-1 ameliorates hypertensive cardiac remodeling by impeding macrophage infiltration
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713306/
https://www.ncbi.nlm.nih.gov/pubmed/36467095
http://dx.doi.org/10.3389/fphar.2022.1058268
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