title: Lipocalin-2 deficiency or blockade protects against aortic abdominal aneurysm development in mice.
abstract: To study the role of lipocalin-2 (Lcn2) and the effect of Lcn2 blockade via anti-Lcn2 antibody in the development of abdominal aortic aneurysm (AAA).
  
  
  
  Expression mRNA and protein levels of Lcn2 and its human orthologue neutrophil gelatinase-associated lipocalin (NGAL) in aortic wall samples from experimental mouse and human AAA samples, respectively, were analysed by real-time PCR and immunohistochemistry. Experimental AAA was induced by aortic elastase perfusion in wild-type mice (WT) and Lcn2-deficient mice (Lcn2-/-). NGAL/Lcn2 mRNA and protein levels in human and murine AAA samples were increased compared with healthy aortas. Decreased AAA incidence and reduced aortic expansion were observed in Lcn2-/- mice or mice preoperative treated with a polyclonal anti-Lcn2 antibody compared with WT mice or mice treated with control IgG, respectively, at Day 14 after elastase perfusion. Moreover, immunohistochemical analysis of AAA tissues from Lcn2-/- or anti-Lcn2-treated mice showed diminished elastin damage, reduced microvessels and polymorphonuclear neutrophil (PMN) infiltration, and enhanced preservation of vascular smooth muscle cells compared with WT aortas. Fluorescent molecular tomography revealed decreased MMP activity in AAA of Lcn2-/- mice compared with WT controls. Therapeutic administration of anti-Lcn2 antibody to WT mice 3 days after elastase perfusion decreased aortic dilatation and PMN infiltration compared with WT mice treated with control IgG.
  
  
  
  Either Lcn2 deficiency or anti-Lcn2 antibody blockade limits AAA expansion in mice by decreasing PMN infiltration in the aorta. Lcn2 modulation may therefore be a viable new therapeutic option for the treatment of AAA.
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Catolicos 2, Madrid 28040, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Tarín
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Catolicos 2, Madrid 28040, Spain.
authors.forename: Carlos Ernesto
authors.initials: CE
authors.lastname: Fernandez-Garcia
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Catolicos 2, Madrid 28040, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Burillo
authors.affiliation: Immunology Research Laboratory, IIS-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Pastor-Vargas
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Catolicos 2, Madrid 28040, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Llamas-Granda
authors.affiliation: Vascular Department, Ramón y Cajal Hospital, IRYCIS, Madrid, Spain.
authors.forename: Borja
authors.initials: B
authors.lastname: Castejón
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Catolicos 2, Madrid 28040, Spain.
authors.forename: Priscila
authors.initials: P
authors.lastname: Ramos-Mozo
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Catolicos 2, Madrid 28040, Spain.
authors.forename: Mónica M
authors.initials: MM
authors.lastname: Torres-Fonseca
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2M9, Canada.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Berger
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2M9, Canada.
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Catolicos 2, Madrid 28040, Spain Universidad Autónoma de Madrid, Madrid, Spain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Catolicos 2, Madrid 28040, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Blanco-Colio
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Catolicos 2, Madrid 28040, Spain Universidad Autónoma de Madrid, Madrid, Spain jlmartin@fjd.es.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Martín-Ventura
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016022:Case-Control Studies; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D000071068:Lipocalin-2 / Q000037:antagonists & inhibitors* / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D000906:Antibodies; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D012333:RNA, Messenger; C071332:Lcn2 protein, mouse; D004549:Elastin; D020782:Matrix Metalloproteinases
keywords: Abdominal aortic aneurysm; Lcn2; MMP; PMN