Role of vascular cell adhesion molecule-1 and fibronectin connecting segment-1 in monocyte rolling and adhesion on early atherosclerotic lesions.

Abstract:

:Atherosclerotic lesion development seems to be inflammatory in nature and involves the recruitment of monocytes to the vessel wall. In this study, we investigated the role of vascular cell adhesion molecule-1 (VCAM-1) and fibronectin (FN) connecting segment-1 containing the amino acid sequence ILDV as functional ligands for alpha(4)beta(1) integrin (VLA-4) in monocyte rolling and adherence to early atherosclerotic lesions. Carotid arteries of apolipoprotein E-deficient mice were isolated and perfused with monocytes or U937 cells. Cell adhesion was reduced 95+/-4% by monoclonal antibodies HP1/2 and HP2/1, which block VLA-4 binding to both VCAM-1 and FN connecting segment-1. mAb HP1/3 preferentially blocked interaction of VLA-4 with FN but not VCAM-1 and decreased adhesion by 30+/-8%. In contrast, blocking VCAM-1 by perfusing the isolated carotid artery with mAb MK-2.7 reduced adhesion by 75+/-12%. Mononuclear cell adhesion to the early atherosclerotic endothelium was inhibited by 68+/-10% in the presence of EILDVPST but not in the presence of control peptide EIDVLPST. When VLA-4 or VCAM-1 was blocked, more mononuclear cells rolled on early lesions at significantly higher (approximately doubled) rolling velocities. These data demonstrate that (1) blockade of VCAM-1 can abrogate the majority (75+/-12%) of VLA-4-dependent monocyte adhesion on early atherosclerotic endothelia and (2) ILDV peptide interferes with VLA-4 binding to both VCAM-1 and FN and may be useful in limiting monocyte adhesion to atherosclerotic lesions.

journal_name

Circ Res

journal_title

Circulation research

authors

Huo Y,Hafezi-Moghadam A,Ley K

doi

10.1161/01.res.87.2.153

subject

Has Abstract

pub_date

2000-07-21 00:00:00

pages

153-9

issue

2

eissn

0009-7330

issn

1524-4571

journal_volume

87

pub_type

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