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Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms.

ABSTRACT: Thoracic aortic aneurysms are life-threatening lesions that afflict young and old individuals alike. They frequently associate with genetic mutations and are characterized by reduced elastic fibre integrity, dysfunctional smooth muscle cells, improperly remodelled collagen and pooled mucoid material. There is a pressing need to understand better the compromised structural integrity of the aorta that results from these genetic mutations and renders the wall vulnerable to dilatation, dissection or rupture. In this paper, we compare the biaxial mechanical properties of the ascending aorta from 10 murine models: wild-type controls, acute elastase-treated, and eight models with genetic mutations affecting extracellular matrix proteins, transmembrane receptors, cytoskeletal proteins, or intracellular signalling molecules. Collectively, our data for these diverse mouse models suggest that reduced mechanical functionality, as indicated by a decreased elastic energy storage capability or reduced distensibility, does not predispose to aneurysms. Rather, despite normal or lower than normal circumferential and axial wall stresses, it appears that intramural cells in the ascending aorta of mice prone to aneurysms are unable to maintain or restore the intrinsic circumferential material stiffness, which may render the wall biomechanically vulnerable to continued dilatation and possible rupture. This finding is consistent with an underlying dysfunctional mechanosensing or mechanoregulation of the extracellular matrix, which normally endows the wall with both appropriate compliance and sufficient strength.

SUBMITTER: Bellini C

PROVIDER: S-EPMC5454287 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms.

Bellini C C Bersi M R MR Caulk A W AW Ferruzzi J J Milewicz D M DM Ramirez F F Rifkin D B DB Tellides G G Yanagisawa H H Humphrey J D JD

Journal of the Royal Society, Interface 20170501 130

Thoracic aortic aneurysms are life-threatening lesions that afflict young and old individuals alike. They frequently associate with genetic mutations and are characterized by reduced elastic fibre integrity, dysfunctional smooth muscle cells, improperly remodelled collagen and pooled mucoid material. There is a pressing need to understand better the compromised structural integrity of the aorta that results from these genetic mutations and renders the wall vulnerable to dilatation, dissection or ...[more]

PMID: 28490606

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Project description:ObjectivesThis study aims to characterize the material properties of ascending thoracic aortic aneurysmal tissue, using regional biomechanical assessment of both tensile and dissection propagation peel strength.MethodsThirty-four aneurysm specimens (proximal thoracic aorta) were harvested en-bloc from patients undergoing surgery for aneurysm replacement. Specimens were processed into regional samples of similar shapes covering the whole aneurysm isosurface, according to a structured protocol, in both orientations (longitudinal and circumferential). Thickness mapping, uniaxial tensile and peel tests were conducted, enabling calculation of the following parameters: true stress/strain, tangential modulus, tensile strength, peeling force and dissection energy. Two constitutive material models were used (hyperelastic models of Delfino and Ogden) to fit the data. A circumferential strip of tissue was also obtained for computational histology [regional quantification of (i) elastin, (ii) collagen and (iii) smooth muscle cells].ResultsThe aortic wall was thinner on the outer curve (2.21, standard deviation (SD) 0.4 mm vs inner curve 2.50, SD 0.12 mm). Advanced patient age and higher pulse wave velocity (externally measured) were predictors of increased aortic wall thickness. Tensile strength was higher in the circumferential versus longitudinal direction when analysed according to anatomical regions. Both peel force (35.5, 22 N/m) and dissection energy (88.5, 69 J/m2) were on average lowest at the outer curve of the aneurysm in the longitudinal orientation. Delfino and Ogden model constants varied throughout anatomical regions, with the outer curve being associated a higher ɑ constant (Delfino) and lower µ1 constant (Ogden) (P < 0.05) indicating increased stiffness. Histologically, collagen abundance was significantly related to circumferential and longitudinal strength (P= 0.010), whilst smooth muscle cell count had no relation with any mechanical property (P > 0.05).ConclusionsOur results suggest that the outer aortic curve is more prone to dissection propagation and perhaps less prone to rupture than the inner aortic curve. This strengthens the notion of disease heterogeneity in ascending thoracic aortic aneurysms and has implications for the pathogenesis of aortic dissection.

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Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms.

Publications

Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms.

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