on June 11, 2009
Published online before print June 11, 2009, doi: 10.1161/ATVBAHA.109.187898
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Submitted on March 11, 2009
Accepted on May 24, 2009
Importance of Junctional Adhesion Molecule-C for Neointimal Hyperplasia and Monocyte Recruitment in Atherosclerosis-Prone Mice
Erdenechimeg Shagdarsuren ;
From the Institute for Molecular Cardiovascular Research (IMCAR) (E.S., Y.D.-T., K.B., E.A.L., C.W., A.Z.), RWTH Aachen University, Germany; UMR891, Inserm (M.A.-L.), Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, France; the Department of Pathology and Immunology (B.A.I.), University Medical Centre, Geneva, Switzerland; and the Rudolf-Virchow-Center (A.Z.), DFG-Research-Center for Experimental Biomedicine, University of Würzburg, Germany.
* To whom correspondence should be addressed. E-mail: azernecke{at}ukaachen.de.
Objective—Although junctional adhesion molecule (JAM)-C has been implicated in the control of inflammatory leukocyte recruitment, its role in neointima formation after arterial injury has not been elucidated.
Methods and Results—In apolipoprotein E–deficient (Apoe-/-) mice fed an atherogenic diet, antibody blockade of JAM-C significantly reduced neointimal hyperplasia after wire injury of carotid arteries without altering medial area and decreased neointimal macrophage but not smooth muscle cell (SMC) content. An increased expression of JAM-C was detected in colocalization with luminal SMCs 1 day after injury and neointimal SMCs after 3 weeks. Blocking JAM-C inhibited monocytic cell arrest and leukocyte adhesion to carotid arteries perfused ex vivo and in vivo. Furthermore, monocyte adhesion to activated coronary artery SMCs under flow conditions in vitro was diminished by blocking JAM-C.
Conclusions—Our data provide the first evidence for a crucial role of JAM-C in accelerated lesion formation and leukocyte recruitment in atherosclerosis-prone mice.
Key words: leukocyte recruitment • adhesion molecules • remodeling • inflammation • restonosis • atherosclerosis