RT Journal Article
T1 Lipocalin-2 deficiency or blockade protects against aortic abdominal aneurysm development in mice
A1 Tarín, Carlos
A1 Fernandez-Garcia, Carlos Ernesto
A1 Burillo, Elena
A1 Pastor Vargas, Carlos
A1 Llamas-Granda, Patricia
A1 Castejón, v
A1 Ramos-Mozo, Priscila
A1 Torres-Fonseca, Mónica M.
A1 Berger, Thorsten
A1 Mak, Tak W.
A1 Egido, Jesús
A1 Blanco-Colio, Luis M.
A1 Martín-Ventura, Jose L.
AB Aims: 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).Methods and results: 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.Conclusion: 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.
PB Oxford Academic
SN 0008-6363
SN 1755-3245
YR 2016
FD 2016
LK https://hdl.handle.net/20.500.14352/107115
UL https://hdl.handle.net/20.500.14352/107115
LA eng
NO Tarín C, Fernandez-Garcia CE, Burillo E, Pastor-Vargas C, Llamas-Granda P, Castejón B, Ramos-Mozo P, Torres-Fonseca MM, Berger T, Mak TW, Egido J, Blanco-Colio LM, Martín-Ventura JL. Lipocalin-2 deficiency or blockade protects against aortic abdominal aneurysm development in mice. Cardiovasc Res. 2016 Aug 1;111(3):262-73. doi: 10.1093/cvr/cvw112. Epub 2016 May 26. PMID: 27229458.
DS Docta Complutense
RD 6 abr 2025