Adhesion molecules and atherogenesis

Yuqing Huo, K. Ley

Research output: Contribution to journalReview article

273 Citations (Scopus)

Abstract

Atherosclerosis is an inflammatory disease of the vessel wall characterized by monocyte infiltration in response to pro-atherogenic factors such as oxidized lipids. Recently, the role of specific adhesion molecules in this process has been explored. The endothelium overlying atherosclerotic lesions expresses P-selectin and the shoulder regions express vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), which is also expressed on endothelium in regions not prone to plaque development. Serum levels of soluble P-selectin, ICAM-1 and VCAM-1 are elevated in patients with angina pectoris or peripheral atherosclerotic disease. Reconstituted in vitro systems using monocytes on cytokine-activated endothelial cells under shear flow suggested the involvement of P-selectin, L-selectin, VCAM-1, its ligand, VLA-4 integrin and CD18 integrins. Studies of monocyte adhesion in isolated perfused carotid arteries harvested from atherosclerotic (apoE-/-) mice show a predominant involvement of P-selectin and its ligand P-selectin glycoprotein-1 (PSGL-1) in rolling and of VLA-4 and VCAM-1 in firm adhesion. Consistent with these findings, apoE-/- mice that are also deficient for P-selectin show significantly reduced atherosclerotic lesion sizes and are almost completely protected from neointimal growth after vascular injury. Milder effects are also seen in the low-density lipoprotein (LDL) receptor deficient (LDLR-/-) mouse. In a high cholesterol/cholate model, a role of ICAM-1 and CD18 integrins was also shown, but this awaits confirmation in more physiologic models. Transient blockade of the VLA-4/VCAM-1 adhesion pathway by antibodies or peptides in apoE-/- or LDLR-/- mice reduced monocyte and lipid accumulation in lesions. These data suggest that P-selectin, PSGL-1, VLA-4 and VCAM-1 are the most important adhesion molecules involved in monocyte recruitment to atherosclerotic lesions.

Original languageEnglish (US)
Pages (from-to)35-43
Number of pages9
JournalActa Physiologica Scandinavica
Volume173
Issue number1
DOIs
StatePublished - Oct 20 2001
Externally publishedYes

Fingerprint

P-Selectin
Vascular Cell Adhesion Molecule-1
Atherosclerosis
Integrin alpha4beta1
Monocytes
Apolipoproteins E
Intercellular Adhesion Molecule-1
Integrins
Endothelium
Cholates
Lipids
L-Selectin
LDL Receptors
Vascular System Injuries
Angina Pectoris
Carotid Arteries
Endothelial Cells
Cholesterol
Cytokines
Ligands

Keywords

  • ApoE-/-mice
  • Atherosclerosis
  • P-selectin
  • PSGL-1
  • VCAM-1
  • VLA-4

ASJC Scopus subject areas

  • Physiology

Cite this

Adhesion molecules and atherogenesis. / Huo, Yuqing; Ley, K.

In: Acta Physiologica Scandinavica, Vol. 173, No. 1, 20.10.2001, p. 35-43.

Research output: Contribution to journalReview article

Huo, Yuqing ; Ley, K. / Adhesion molecules and atherogenesis. In: Acta Physiologica Scandinavica. 2001 ; Vol. 173, No. 1. pp. 35-43.
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