1. Academic Validation
  2. Blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding macrophage infiltration

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

  • Front Pharmacol. 2022 Nov 17:13:1058268. doi: 10.3389/fphar.2022.1058268.
Ze-Yang Qiu 1 Wei-Jia Yu 1 Jie Bai 1 Qiu-Yue Lin 1
Affiliations

Affiliation

  • 1 Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Abstract

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.

Keywords

VCAM-1; cardiac remodeling; hypertension; inflammation; macrophage infiltration.

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