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Atherosclerosis. 2014 Jun;234(2):254-64. doi: 10.1016/j.atherosclerosis.2014.03.014. Epub 2014 Mar 25.

Atherogenic mononuclear cell recruitment is facilitated by oxidized lipoprotein-induced endothelial junctional adhesion molecule-A redistribution.

Author information

1
Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany; Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
2
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany.
3
Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
4
Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
5
Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. Electronic address: r.koenen@maastrichtuniversity.nl.

Abstract

BACKGROUND:

Junctional adhesion molecule (JAM-) A is a transmembrane protein expressed in many cell types and maintains junctional integrity in endothelial cells. Upon inflammatory stimulation, JAM-A relocates to the apical surface and might thereby facilitate the recruitment of leukocytes.

OBJECTIVE:

Although inflammatory JAM-A redistribution is an established process, further effort is required to understand its exact role in the transmigration of mononuclear cells, particularly under atherogenic conditions.

METHODS:

By the use of RNA interference and genetic deletion, the role of JAM-A in the transmigration of T cells and monocytes through aortic endothelial cells was investigated. JAM-A-localization and subsequent mononuclear cell rolling, adhesion and transmigration were explored during endothelial inflammation, induced by oxidized LDL or cytokines.

RESULTS:

RNA interference or genetic deletion of JAM-A in aortic endothelial cells resulted in a decreased transmigration of mononuclear cells. Treatment of the endothelial cells with oxLDL resulted in an increase of both permeability and apical JAM-A presentation, as shown by bead adhesion and confocal microscopy experiments. Redistribution of JAM-A resulted in an increased leukocyte adhesion and transmigration, which could be inhibited with antibodies against JAM-A or by lovastatin-treatment, but not with the peroxisome proliferator activated receptor gamma-agonist pioglitazone.

CONCLUSIONS:

This study demonstrates that redistribution of JAM-A in endothelial cells after stimulation with pro-atherogenic oxidized lipoproteins results in increased transmigration of mononuclear cells. This inflammatory dispersal of JAM-A could be counteracted with statins, revealing a novel aspect of their mechanism of action.

KEYWORDS:

Atherosclerosis; Endothelial cells; F11R; JAM-1; Junctional adhesion molecule; Statin; Transmigration

[Indexed for MEDLINE]

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