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Biomechanical consequences of compromised elastic fiber integrity and matrix cross-linking on abdominal aortic aneurysmal enlargement

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Biomechanical consequences of compromised elastic fiber integrity and matrix cross-linking on abdominal aortic aneurysmal enlargement

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dc.contributor.author Weiss, D. es_ES
dc.contributor.author Latorre, Marcos es_ES
dc.contributor.author Rego, B., V. es_ES
dc.contributor.author Cavinato, C. es_ES
dc.contributor.author Tanski, B. J. es_ES
dc.contributor.author Berman, A. G. es_ES
dc.contributor.author Goergen, C. J. es_ES
dc.contributor.author Humphrey, Jay D. es_ES
dc.date.accessioned 2023-01-24T19:00:55Z
dc.date.available 2023-01-24T19:00:55Z
dc.date.issued 2021-10-15 es_ES
dc.identifier.issn 1742-7061 es_ES
dc.identifier.uri http://hdl.handle.net/10251/191454
dc.description.abstract [EN] Abdominal aortic aneurysms (AAAs) are characterized histopathologically by compromised elastic fiber integrity, lost smooth muscle cells or their function, and remodeled collagen. We used a recently introduced mouse model of AAAs that combines enzymatic degradation of elastic fibers and blocking of lysyl oxidase, and thus matrix cross-linking, to study progressive dilatation of the infrarenal abdominal aorta, including development of intraluminal thrombus. We quantified changes in biomaterial properties and biomechanical functionality within the aneurysmal segment as a function of time of enlargement and degree of thrombosis. Towards this end, we combined multi-modality imaging with state-of-the-art biomechanical testing and histology to quantify regional heterogeneities for the first time and we used a computational model of arterial growth and remodeling to test multiple hypotheses, suggested by the data, regarding the degree of lost elastin, accumulation of glycosaminoglycans, and rates of collagen turnover. We found that standard histopathological findings can be misleading, while combining advanced experimental and computational methods revealed that glycosaminoglycan accumulation is pathologic, not adaptive, and that heightened collagen deposition is ineffective if not cross-linked. In conclusion, loss of elastic fiber integrity can be a strong initiator of aortic aneurysms, but it is the rate and effectiveness of fibrillar collagen remodeling that dictates enlargement. es_ES
dc.description.sponsorship This work was supported, in part, by grants from the US National Institutes of Health (U01 HL142518 to JDH), American Heart Association (12SDG18220010 to CJG), NSF (Graduate Student Research Fellowship to AGB), and the Leslie A. Geddes Endowment at Purdue University es_ES
dc.language Inglés es_ES
dc.publisher Elsevier es_ES
dc.relation.ispartof Acta Biomaterialia es_ES
dc.rights Reconocimiento - No comercial - Sin obra derivada (by-nc-nd) es_ES
dc.subject Elastase es_ES
dc.subject BAPN es_ES
dc.subject Collagen cross-linking es_ES
dc.subject Abdominal aortic aneurysms es_ES
dc.title Biomechanical consequences of compromised elastic fiber integrity and matrix cross-linking on abdominal aortic aneurysmal enlargement es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1016/j.actbio.2021.07.059 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/AHA//12SDG18220010/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/NIH//U01 HL142518//Multimodality imaging-driven multifidelity modeling of aortic dissection/ es_ES
dc.rights.accessRights Abierto es_ES
dc.description.bibliographicCitation Weiss, D.; Latorre, M.; Rego, BV.; Cavinato, C.; Tanski, BJ.; Berman, AG.; Goergen, CJ.... (2021). Biomechanical consequences of compromised elastic fiber integrity and matrix cross-linking on abdominal aortic aneurysmal enlargement. Acta Biomaterialia. 134:422-434. https://doi.org/10.1016/j.actbio.2021.07.059 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1016/j.actbio.2021.07.059 es_ES
dc.description.upvformatpinicio 422 es_ES
dc.description.upvformatpfin 434 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 134 es_ES
dc.identifier.pmid 34332103 es_ES
dc.identifier.pmcid PMC8542633 es_ES
dc.relation.pasarela S\472494 es_ES
dc.contributor.funder American Heart Association es_ES
dc.contributor.funder National Institutes of Health, EEUU es_ES
dc.subject.ods 03.- Garantizar una vida saludable y promover el bienestar para todos y todas en todas las edades es_ES


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