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Tumor necrosis factor-like weak inducer of apoptosis or Fn14 deficiency reduce elastase perfusion-induced aortic abdominal aneurysm in mice
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نویسنده
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tarín c. ,ferńandez-laso v. ,sastre c. ,madrigal-matute j. ,gómez m. ,zaragoza c. ,egido j. ,burkly l.c. ,martín-ventura j.l. ,blanco-colio l.m.
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منبع
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journal of the american heart association - 2014 - دوره : 3 - شماره : 4
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چکیده
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Background-abdominal aortic aneurysm (aaa) involves leukocyte recruitment,inflammatory cytokine production,vascular cell apoptosis,neovascularization,and vascular remodeling,all of which contribute to aortic dilatation. tumor necrosis factor-like weak inducer of apoptosis (tweak) is a cytokine implicated in proinflammatory responses,angiogenesis,and matrix degradation but its role in aaa formation is currently unknown. methods and results-experimental aaa with aortic elastase perfusion in mice was induced in wild-type (wt),tweak deficient (tweak ko),or fn14-deficient (fn14 ko) mice. tweak or fn14 ko deficiency reduced aortic expansion,lesion macrophages,cd3+ t cells,neutrophils,cd31+ microvessels,ccl2 and ccl5 chemokines expression,and mmp activity after 14 days postperfusion. tweak and fn14 ko mice also showed a reduced loss of medial vascular smooth muscle cells (vsmc) that was related to a reduced number of apoptotic cells in these animals compared with wt mice. aortas from wt animals present a higher disruption of the elastic layer and mmp activity than those from tweak or fn14 ko mice,indicating a diminished vascular remodeling in ko animals. in vitro experiments unveiled that tweak induces ccl5 secretion and mmp-9 activation in both vsmc and bone marrow-derived macrophages,and decrease vsmc viability,effects dependent on fn14. conclusions-tweak/fn14 axis participates in aaa formation by promoting lesion inflammatory cell accumulation,angiogenesis,matrix-degrading protease expression,and vascular remodeling. blocking tweak/fn14 interaction could be a new target for the treatment of aaa. © 2014 the authors.
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کلیدواژه
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Aneurysm; Fn14; Inflammation; MMP activity; TWEAK
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آدرس
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iis-fundacíon jiménez díaz,vascular research lab,madrid, Spain, iis-fundacíon jiménez díaz,vascular research lab,madrid, Spain, iis-fundacíon jiménez díaz,vascular research lab,madrid, Spain, iis-fundacíon jiménez díaz,vascular research lab,madrid, Spain, spanish national cardiovascular research center,madrid, Spain, cardiovascular joint research unit,university hospital ramón cajal hospital,university francisco de vitoria,school of medicine,madrid, Spain, iis-fundacíon jiménez díaz,vascular research lab,madrid, Spain, biogen idec,cambridge,ma, United States, iis-fundacíon jiménez díaz,vascular research lab,madrid, Spain, iis-fundacíon jiménez díaz,vascular research lab,madrid, Spain
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Authors
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