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

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.

CD11b mediates hypertensive cardiac remodeling by regulating macrophage infiltration and polarization

“…Increasing evidence indicates that CD11b/CD18 binding to its ligands (ICAM-1 and VCAM-1) predominantly mediates leukocyte adhesion to the endothelium and plays an important role in some cardiovascular diseases [18] . Deficiency or blockade of ICAM-1 and VCAM-1 markedly decreased the infiltration of monocytes and T cells of heart and alleviated pressure overload- or Ang II-caused cardiac remodeling [10] , [11] , [13] , [19] , [20] . In addition to CD11b/CD18-ICAM-1 signaling, integrin-α4β1/VLA-4-VCAM interactions also promotes adhesion and infiltration of CD11b + monocytes/MΦs in tumors [21] .…”

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

“…BMI1 [245] and SNCA (synuclein alpha) [251] have been known to be involved in kidney fibrosis progression. BMI1 [260], VCAM1 [321], ALB (albumin) [326] and DPP4 [309] have a significant prognostic potential in hypertension. BMI1 [327], VCAM1 [376], ALB (albumin) [377] and DPP4 [369] are molecular markers for the diagnosis and prognosis of AKI.…”

“…E2F1 [110], BMI1 [95], EEF1A2 [104], ACTA1 [128], VCAM1 [220], AGTR1 [58], hsa-mir-221 [784], MEF2A [785], FOXC1 [786], YY1 [787], STAT3 [788] and BRCA1 [789] were significantly associated with cardiovascular disorders. E2F1 [265], BMI1 [260], VCAM1 [321], AGTR1 [64], hsa-mir-638 [790], hsa-mir-221 [791], FOXC1 [792], YY1 [793], STAT3 [794] and BRCA1 [795] provided a clear picture of the prognosis of patients with hypertension. E2F1 [329], BMI1 [327], VCAM1 [376], USF2 [796], YY1 [797], STAT3 [798] and BRCA1 [799] have always been found in AKI.…”

Transcriptome and proteome analyses reveal that upregulation of GSTM2 by allisartan improves cardiac remodeling and dysfunction in hypertensive rats

“…As the disease progressed, heart function further deteriorated at 48 weeks, consistent with the entire process of the occurrence and development of hypertensive heart disease. The morphological changes in the myocardial tissue of SHRs were manifested by cardiomyocyte hypertrophy, collagen deposition and increased expression of myocardial fibrosis markers, indicating typical cardiac remodeling ( 40 ). Treatment with allisartan effectively controlled the blood pressure of SHRs and, by 28 weeks, cardiac remodeling and functional impairment were improved.…”