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

Yuqing Huo, Ali Hafezi-Moghadam, Klaus Ley

Research output: Contribution to journalArticle

161 Citations (Scopus)

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 α4β1 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.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalCirculation research
Volume87
Issue number2
DOIs
StatePublished - Jul 21 2000

Fingerprint

Integrin alpha4beta1
Vascular Cell Adhesion Molecule-1
Monocytes
Carotid Arteries
Fibronectins
Cell Adhesion
Endothelium
U937 Cells
Peptides
Apolipoproteins E
CS1 peptide
Integrins
Amino Acid Sequence
Monoclonal Antibodies
Ligands

Keywords

  • Atherosclerosis
  • Connecting segment-1
  • Fibronectin
  • Monocyte
  • Vascular cell adhesion molecule-1

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Role of vascular cell adhesion molecule-1 and fibronectin connecting segment-1 in monocyte rolling and adhesion on early atherosclerotic lesions. / Huo, Yuqing; Hafezi-Moghadam, Ali; Ley, Klaus.

In: Circulation research, Vol. 87, No. 2, 21.07.2000, p. 153-159.

Research output: Contribution to journalArticle

@article{4e7abaaf1a8f40b38c2a90cae7afefcd,
title = "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 α4β1 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.",
keywords = "Atherosclerosis, Connecting segment-1, Fibronectin, Monocyte, Vascular cell adhesion molecule-1",
author = "Yuqing Huo and Ali Hafezi-Moghadam and Klaus Ley",
year = "2000",
month = "7",
day = "21",
doi = "10.1161/01.RES.87.2.153",
language = "English (US)",
volume = "87",
pages = "153--159",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Role of vascular cell adhesion molecule-1 and fibronectin connecting segment-1 in monocyte rolling and adhesion on early atherosclerotic lesions

AU - Huo, Yuqing

AU - Hafezi-Moghadam, Ali

AU - Ley, Klaus

PY - 2000/7/21

Y1 - 2000/7/21

N2 - 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 α4β1 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.

AB - 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 α4β1 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.

KW - Atherosclerosis

KW - Connecting segment-1

KW - Fibronectin

KW - Monocyte

KW - Vascular cell adhesion molecule-1

UR - http://www.scopus.com/inward/record.url?scp=0034698125&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034698125&partnerID=8YFLogxK

U2 - 10.1161/01.RES.87.2.153

DO - 10.1161/01.RES.87.2.153

M3 - Article

C2 - 10904000

AN - SCOPUS:0034698125

VL - 87

SP - 153

EP - 159

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 2

ER -