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Technical Brief

Biomechanical Phenotyping of the Murine Aorta: What Is the Best Control?

[+] Author and Article Information
C. Bellini, A. W. Caulk

Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520

G. Li

Department of Surgery,
Yale School of Medicine,
New Haven, CT 06520

G. Tellides

Department of Surgery,
Yale School of Medicine,
New Haven, CT 06520;
Vascular Biology and Therapeutics Program,
Yale School of Medicine,
New Haven, CT 06520

J. D. Humphrey

Fellow ASME
Department of Biomedical Engineering,
Yale University,
55 Prospect Street,
New Haven, CT 06520;
Vascular Biology and Therapeutics Program,
Yale School of Medicine,
New Haven, CT 06520
e-mail: jay.humphrey@yale.edu

1Corresponding author.

Manuscript received October 11, 2016; final manuscript received December 16, 2016; published online January 31, 2017. Assoc. Editor: Jonathan Vande Geest.

J Biomech Eng 139(4), 044501 (Jan 31, 2017) (6 pages) Paper No: BIO-16-1400; doi: 10.1115/1.4035551 History: Received October 11, 2016; Revised December 16, 2016

The availability of diverse mouse models is revealing increasingly greater information on arterial mechanics, including homeostatic adaptations and pathologic maladaptations to genetic, pharmacological, and surgical manipulations. Fundamental to understanding such biomechanical changes, however, is reliable information on appropriate control vessels. In this paper, we contrast 15 different geometrical and mechanical metrics of biaxial wall mechanics for the ascending aorta across seven different types of possible control mice. We show that there is a comforting similarity across these multiple controls for most, though not all, metrics. In particular, three potential controls, namely, noninduced conditional mice, exhibit higher values of distensibility, an important clinical metric of structural stiffness, and two of these potential controls also have higher values of intrinsic circumferential material stiffness. There is motivation, therefore, to understand better the biomechanical changes that can arise with noninduced Cre-lox or similar approaches for generating mutations conditionally. In cases of germline mutations generated by breeding heterozygous +/− mice, however, the resulting homozygous +/+ mice tend to exhibit properties similar to traditional (C57BL/6) controls.

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Figures

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Fig. 1

Mechanical data from cyclic in vitro biaxial testing reveal similar structural, (a) and (b), and material, (c) and (d), behaviors across the seven groups of potential control mice. The black symbols show homozygous nonmutant littermate mice (+/+) generated by breeding heterozygous mutant mice (+/−), the gray symbol indicates pure C57BL/6J wild-type mice, and open symbols show noninduced mice in which mutations could be induced conditionally with tamoxifen. Veh indicates treatment with vehicle rather than tamoxifen. The error bars represent the standard error of the mean (SEM).

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Fig. 2

Geometrical and mechanical metrics are mostly similar across the seven groups of potential controls and do not appear to depend on age over the range from 8 to 27 weeks. Greyscale conventions for symbols follow Fig. 1 and error bars again represent the SEM. The gray shaded region in each plot defines ranges of values for the average adult control male mice obtained by pooling the four groups that were not statistically different (i.e., Myh11+/+, Fbn1+/+, Fbln5+/+, and C57BL/6J). Noninduced mice (Fbln4loxP/+, mT/mG.Myh11-CreERT2.Tgfbr2f/f + Veh, and mT/mG.Myh11-CreERT2.Tsc1f/f + Veh) show slight differences in multiple metrics (unloaded thickness, outer/inner diameter, stretch, stress, stiffness, and distensibility), which include circumferential properties.

Grahic Jump Location
Fig. 3

Unloaded outer diameter (OD), outer diameter at systole (od), and distensibility (D) are the only metrics that seem to correlate with the body mass of the mice. Color conventions for symbols follow Figs. 1 and 2. Again, the error bars represent the SEM and the gray shaded area in each plot identifies the expected behavior of an average adult control male mouse. It is noted that two of the three noninduced mice had lower body mass than average.

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