title: Deletion of junctional adhesion molecule A from platelets increases early-stage neointima formation after wire injury in hyperlipidemic mice.
abstract: Platelets play an important role in the pathogenesis of vascular remodelling after injury. Junctional adhesion molecule A (JAM-A) was recently described to regulate platelet activation. Specific deletion of JAM-A from platelets resulted in increased reactivity and in accelerated progression of atherosclerosis. The aim of this study was to investigate the specific contribution of platelet-derived JAM-A to neointima formation after vascular injury. Mice with or without platelet-specific (tr)JAM-A-deficiency in an apolipoprotein e (apoe-/-) background underwent wire-induced injury of the common carotid artery. Ex vivo imaging by two-photon microscopy revealed increased platelet coverage at the site of injury in trJAM-A-deficient mice. Cell recruitment assays showed increased adhesion of monocytic cells to activated JAM-A-deficient platelets than to control platelets. Inhibition of αMβ2or GPIbα, but not of CD62P, suppressed those differences. Up to 4 weeks after wire injury, intimal neoplasia and neointimal cellular content were analysed. Neointimal lesion area was increased in trJAM-A-/-apoe-/-mice and the lesions showed an increased macrophage accumulation and proliferating smooth muscle cells compared with trJAM-A+/+apoe-/-littermates 2 weeks, but not 4 weeks after injury. Re-endothelialization was decreased in trJAM-A-/-apoe-/-mice compared with controls 2 weeks after injury, yet it was complete in both groups after 4 weeks. A platelet gain of function by deletion of JAM-A accelerates neointima formation only during earlier phases after vascular injury, through an increased recruitment of mononuclear cells. Thus, the contribution of platelets might become less important when neointima formation progresses to later stages.
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany.|Division of Vascular and Endovascular Surgery, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Tanja
authors.initials: T
authors.lastname: Vajen
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Ela
authors.initials: E
authors.lastname: Karshovska
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Annemiek
authors.initials: A
authors.lastname: Dickhout
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Schmitt
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany.|Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Remco T A
authors.initials: RTA
authors.lastname: Megens
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: von Hundelshausen
authors.affiliation: Division of Vascular and Endovascular Surgery, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Koeppel
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Tilman M
authors.initials: TM
authors.lastname: Hackeng
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany.|Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Rory R
authors.identifier: 0000-0002-9955-9730
authors.initials: RR
authors.lastname: Koenen
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006949:Hyperlipidemias / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D058426:Neointima / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction; D066253:Vascular Remodeling / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; C498686:F11r protein, mouse; D011956:Receptors, Cell Surface
keywords: junctional adhesion molecule; leucocyte; neointima; platelet