This Article Full Text Full Text (PDF) All Versions of this Article: 26/2/e10    most recent 01.ATV.0000197852.24529.4fv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zernecke, A. Articles by Weber, C. Search for Related Content PubMed PubMed Citation Articles by Zernecke, A. Articles by Weber, C. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Medline Plus Health Information Carotid Artery Disease

(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

This article has been cited by other articles:

				J. M. van Gils, J. J. Zwaginga, and P. L. Hordijk Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases J. Leukoc. Biol., February 1, 2009; 85(2): 195 - 204. [Abstract] [Full Text] [PDF]

				Y.-L. Guo, R. Bai, C. X-J Chen, D.-Q. Liu, Y. Liu, C.-Y. Zhang, and K. Zen Role of Junctional Adhesion Molecule-Like Protein in Mediating Monocyte Transendothelial Migration Arterioscler Thromb Vasc Biol, January 1, 2009; 29(1): 75 - 83. [Abstract] [Full Text] [PDF]

				A. Schober Chemokines in Vascular Dysfunction and Remodeling Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1950 - 1959. [Abstract] [Full Text] [PDF]

				E. J.A. van Wanrooij, P. de Vos, M. G. Bixel, D. Vestweber, T. J.C. van Berkel, and J. Kuiper Vaccination against CD99 inhibits atherogenesis in low-density lipoprotein receptor-deficient mice Cardiovasc Res, June 1, 2008; 78(3): 590 - 596. [Abstract] [Full Text] [PDF]

				E. Galkina and K. Ley Vascular Adhesion Molecules in Atherosclerosis Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2292 - 2301. [Abstract] [Full Text] [PDF]

				R. Krohn, U. Raffetseder, I. Bot, A. Zernecke, E. Shagdarsuren, E. A. Liehn, P. J. van Santbrink, P. J. Nelson, E. A. Biessen, P. R. Mertens, et al. Y-Box Binding Protein-1 Controls CC Chemokine Ligand-5 (CCL5) Expression in Smooth Muscle Cells and Contributes to Neointima Formation in Atherosclerosis-Prone Mice Circulation, October 16, 2007; 116(16): 1812 - 1820. [Abstract] [Full Text] [PDF]

				P. F. Bradfield, S. Nourshargh, M. Aurrand-Lions, and B. A. Imhof JAM Family and Related Proteins in Leukocyte Migration (Vestweber Series) Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2104 - 2112. [Abstract] [Full Text] [PDF]

				P. von Hundelshausen and C. Weber Platelets as Immune Cells: Bridging Inflammation and Cardiovascular Disease Circ. Res., January 5, 2007; 100(1): 27 - 40. [Abstract] [Full Text] [PDF]

				M. Lucerna, A. Zernecke, R. de Nooijer, S. C. de Jager, I. Bot, C. van der Lans, I. Kholova, E. A. Liehn, T. J. C. van Berkel, S. Yla-Herttuala, et al. Vascular endothelial growth factor-A induces plaque expansion in ApoE knock-out mice by promoting de novo leukocyte recruitment Blood, January 1, 2007; 109(1): 122 - 129. [Abstract] [Full Text] [PDF]