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Outside-in signaling by femoral cuff injury induces a distinct vascular lesion in adipose triglyceride lipase knockout mice

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dc.contributor.authorNoguchi, Hirotsugu
dc.contributor.authorYamada, Sohsuke
dc.contributor.authorHirano, Ken Ichi
dc.contributor.authorYamaguchi, Satoshi
dc.contributor.authorSuzuki, Akira
dc.contributor.authorGuo, Xin
dc.contributor.authorZaima, Nobuhiro
dc.contributor.authorLi, Ming
dc.contributor.authorKobayashi, Kunihisa
dc.contributor.authorIkeda, Yoshihiko
dc.contributor.authorNakayama, Toshiyuki
dc.contributor.authorSasaguri, Yasuyuki
dc.date.accessioned2022-12-02T10:51:10Z
dc.date.available2022-12-02T10:51:10Z
dc.date.issued2021
dc.description.abstractGenetic deficiency of adipose triglyceride lipase (ATGL), a rate-limiting enzyme for intracellular triglyceride (TG) hydrolysis, causes TG-deposit cardiomyovasculopathy (TGCV), a recently identified rare cardiovascular disorder (ORPHA code: 565612) in humans. One of the major characteristics of TGCV is a novel type of diffuse and concentric coronary atherosclerosis with ATGL-deficient smooth muscle cells (SMCs). Patients with TGCV have intractable coronary artery disease. Therefore, it is crucial to investigate the mechanisms underlying vascular lesions in ATGL deficiency using animal models. Cuff injury is an experimental procedure to induce vascular remodeling with neointimal formation with SMCs after placing a cuff around the adventitial side of the artery without direct influence on endothelium. We report the effect of cuff injury on femoral arteries of ATGLknockout (ATGL–/–) mice. Cuff-induced concentric neointimal formation with migrating SMCs was exacerbated in ATGL–/– mice, mimicking atherosclerotic lesions in patients with TGCV. In the media, cell death of SMCs and loss of elastic fibers increased. Perivascular infiltrating cells expressing tumor necrosis factor-α (TNF-α) were more prominent in ATGL–/– mice than in wild-type (WT) mice. In Boyden chamber experiments, a greater number of ATGL–/– SMCs migrated in response to TNF-α compared to WT SMCs. These data, for the first time, demonstrated that outsidein signaling by cuff-induced neointimal formation where paracrine stimuli from adventitial infiltrating cells may lead to neointimal formation and mediolysis in ATGLdeficient conditions. Cuff injury might be a valuable model for understanding the mechanisms underlying the development of atherosclerotic lesions in patients with TGCVes
dc.formatapplication/pdfes
dc.format.extent10es
dc.identifier.citationHistology and Histopathology, Vol.36, nº1, (2021)
dc.identifier.doi10.14670/HH-18-285
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/126169
dc.languageenges
dc.publisherUniversidad de Murcia. Departamento de Biología Celular e Histologíaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAdipose triglyceride lipasees
dc.subjectCuff injuryes
dc.subjectOutside-in signalinges
dc.subjectSmooth muscle celles
dc.subjectTriglyceride deposit cardiomyovasculopathyes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleOutside-in signaling by femoral cuff injury induces a distinct vascular lesion in adipose triglyceride lipase knockout micees
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.36, nº1 (2021)