IG9 monocyte adhesion molecule expression is induced in vivo in a hypercholesterolemic rabbit model of atherosclerosis and is differentially regulated in vitro in human vascular endothelial and smooth muscle cells

T. M. Calderon, S. David Gertz, Mark B. Taubman, Judith A. Berliner, Ian J. Sarembock, Lawrence W. Gimple, John T. Fallon, J. W. Berman

Research output: Contribution to journalArticle

Abstract

Neo-intimal accumulation of monocytes is critical in the pathogenesis of atherosclerosis. We have previously characterized the IG9 monocyte adhesion protein, expressed in vitro on cytokine, LPS or minimally oxidized LDL (mmLDL)-activated human endothelial cells (EC) and in vivo on EC overlying advanced human and rabbit atherosclerotic plaques. To characterize IG9 expression during lesion development, vessel sections from rabbits fed a hypercholesterolemic diet in combination with femoral artery EC injury by nitrogen/air desiccation and/or balloon angioplasty were analyzed immunohistochemically. IG9 reactivity was detected in large areas of the medial smooth muscle cell (SMC) layer very early after vessel injury and later time points revealed EC specific expression of IG9 and neo-intimal SMC and foam cell reactivity. ELISA assays with human EC and SMC revealed distinct differences in inducible IG9 expression in vitro in that EC cultures treated with TNFα, IL-1 or LPS alone for 3-24 hr expressed IG9 (OD of ≈ 1) but SMC did not. PDGF alone had no effect on SMC (OD ≈ 0.05) but in combination with TNFα, LPS, EGF or phorbol ester (PMA) for 16-48 hr. induced moderate IG9 protein expression (OD ≈ 0.2). This induction was further augmented by the addition of mmLDL (OD ≈ 0.4). Thus, distinct biochemical signals seem to induce IG9 in EC versus SMC. The expression of this protein by the two major cell types within the vessel wall may function as a key mediator of monocytic infiltration during the early stages of injury-induced atherogenesis in hypercholesterolemic rabbits.

Original languageEnglish (US)
Pages (from-to)A1140
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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