Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice

Simple item page
dc.contributor.authorCristina Sastre
dc.contributor.authorValvanera Fernández‐Laso
dc.contributor.authorJulio Madrigal‐Matute
dc.contributor.authorBegoña Muñoz‐García
dc.contributor.authorJuan A. Moreno
dc.contributor.authorPastor Vargas, Carlos
dc.contributor.authorPatricia Llamas‐Granda
dc.contributor.authorLinda C. Burkly
dc.contributor.authorJesús Egido
dc.contributor.authorJose L. Martín‐Ventura
dc.contributor.authorLuis M. Blanco‐Colio
dc.date.accessioned2024-07-31T11:56:47Z
dc.date.available2024-07-31T11:56:47Z
dc.date.issued2014-01-30
dc.description.abstractClinical complications associated with atherosclerotic plaques arise from luminal obstruction due to plaque growth or destabilization leading to rupture. Tumour necrosis factor ligand superfamily member 12 (TNFSF12) also known as TNF-related weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine that participates in atherosclerotic plaque development, but its role in plaque stability remains unclear. Using two different approaches, genetic deletion of TNFSF12 and treatment with a TWEAK blocking mAb in atherosclerosis-prone mice, we have analysed the effect of TWEAK inhibition on atherosclerotic plaques progression and stability. Mice lacking both TNFSF12 and Apolipoprotein E (TNFSF12(-/-) ApoE(-/-) ) exhibited a diminished atherosclerotic burden and lesion size in their aorta. Advanced atherosclerotic plaques of TNFSF12(-/-) ApoE(-/-) or anti-TWEAK treated mice exhibited an increase collagen/lipid and vascular smooth muscle cell/macrophage ratios compared with TNFSF12(+/+) ApoE(-/-) control mice, reflecting a more stable plaque phenotype. These changes are related with two different mechanisms, reduction of the inflammatory response (chemokines expression and secretion and nuclear factor kappa B activation) and decrease of metalloproteinase activity in atherosclerotic plaques of TNFSF12(-/-) ApoE(-/-) . A similar phenotype was observed with anti-TWEAK mAb treatment in TNFSF12(+/+) ApoE(-/-) mice. Brachiocephalic arteries were also examined since they exhibit additional features akin to human atherosclerotic plaques associated with instability and rupture. Features of greater plaque stability including augmented collagen/lipid ratio, reduced macrophage content, and less presence of lateral xanthomas, buried caps, medial erosion, intraplaque haemorrhage and calcium content were present in TNFSF12(-/-) ApoE(-/-) or anti-TWEAK treatment in TNFSF12(+/+) ApoE(-/-) mice. Overall, our data indicate that anti-TWEAK treatment has the capacity to diminish proinflamatory response associated with atherosclerotic plaque progression and to alter plaque morphology towards a stable phenotype.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Ciencias Químicas
dc.description.fundingtypePagado por el autor
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationSastre C, Fernández-Laso V, Madrigal-Matute J, Muñoz-García B, Moreno JA, Pastor-Vargas C, Llamas-Granda P, Burkly LC, Egido J, Martín-Ventura JL, Blanco-Colio LM. Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice. J Cell Mol Med. 2014 Apr;18(4):721-34. doi: 10.1111/jcmm.12221. Epub 2014 Jan 30. PMID: 24479820; PMCID: PMC4000122.
dc.identifier.doi10.1111/jcmm.12221
dc.identifier.issn1582-1838
dc.identifier.issn1582-4934
dc.identifier.officialurlhttps://doi.org/10.1111/jcmm.12221
dc.identifier.relatedurlhttps://onlinelibrary.wiley.com/doi/10.1111/jcmm.12221
dc.identifier.urihttps://hdl.handle.net/20.500.14352/107322
dc.issue.number4
dc.journal.titleJournal of Cellular and Molecular Medicine
dc.language.isoeng
dc.page.final734
dc.page.initial721
dc.publisherWiley
dc.relation.projectIDThis study was supported by FIS (Programa Estabilización Investigadores to LB-C, Miguel Servet to JAM), Instituto de Salud Carlos III (RETICS RD12/0042/0038; PI10/00234; PI10/00072; PI13/00395), Sociedad Española de Arteriosclerosis, Fundación Mútua Madrileña and a research grant from Biogen Idec (to LB-C).
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu611.1
dc.subject.cdu616.13-002.2
dc.subject.keywordTWEAK
dc.subject.keywordAtherosclerosis
dc.subject.keywordInflammation
dc.subject.keywordPlaque stability
dc.subject.ucmMedicina
dc.subject.ucmSistema cardiovascular
dc.subject.unesco32 Ciencias Médicas
dc.subject.unesco3207 Patología
dc.subject.unesco3207.02 Arteriosclerosis
dc.titleGenetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number18
dspace.entity.typePublication
relation.isAuthorOfPublication25af78c7-0077-4891-a14e-bcd8e51fe408
relation.isAuthorOfPublication.latestForDiscovery25af78c7-0077-4891-a14e-bcd8e51fe408
Download
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Genetic deletion or TWEAK blocking antibody administration.pdf
Size:
1.02 MB
Format:
Adobe Portable Document Format
downoload Download
Collections
Artículos