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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:e10.)
© 2006 American Heart Association, Inc.

Vascular Biology

Importance of Junctional Adhesion Molecule-A for Neointimal Lesion Formation and Infiltration in Atherosclerosis-Prone Mice

Alma Zernecke; Elisa A. Liehn; Line Fraemohs; Philipp von Hundelshausen; Rory R. Koenen; Monica Corada; Elisabetta Dejana; Christian Weber

From the Department of Molecular Cardiovascular Research (A.Z., E.A.L., L.F., P.v.H., R.R.K., C.W.), RWTH University Hospital, Aachen, Germany; Mario Negri Institute for Pharmacological Research and FIRC Institute of Molecular Oncology (M.C., E.D.); and the Department of Biomolecular and Biotechnological Sciences School of Sciences (E.D.), University of Milan, Italy.

Correspondence to Dr Christian Weber, Kardiovaskuläre Molekularbiologie, Universitätsklinikum Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany. E-mail cweber{at}ukaachen.de

Objective— Although junctional adhesion molecule-A (JAM-A) has recently been implicated in leukocyte recruitment on early atherosclerotic endothelium and after reperfusion injury, its role in neointima formation after arterial injury remains to be elucidated.

Methods and Results— Here we show that the genetic deletion of JAM-A in apolipoprotein E–deficient (apoE^–/–) mice significantly reduced neointimal hyperplasia after wire injury of carotid arteries without altering medial area. This was associated with a significant decrease in neointimal macrophage content, whereas the relative content of smooth muscle cells and endothelial recovery was unaltered in JAM-A^–/–apoE^–/– compared with JAM-A^+/+apoE^–/– lesions. In carotid arteries perfused ex vivo, deficiency in JAM-A significantly impaired the recruitment of monocytes 1 week, but not 1 day, after injury. These effects were paralleled by an attenuation of monocyte arrest and transmigration on activated JAM-A^–/–apoE^–/– versus JAM-A^+/+apoE^–/– endothelial cells under flow conditions in vitro. A mechanism underlying reduced recruitment was implied by findings that the luminal expression of the arrest chemokine RANTES in injured arteries and its endothelial deposition by activated platelets in vitro were diminished by JAM-A deficiency.

Conclusions— Our data provide the first evidence to our knowledge for a crucial role of JAM-A in accelerated lesion formation and monocyte infiltration in atherosclerosis-prone mice.

Key Words: adhesion molecule • atherosclerosis • chemokine • monocytes

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