Consistent Biomechanical Phenotyping of Common Carotid Arteries from Seven Genetic, Pharmacological, and Surgical Mouse Models

Abstract

The continuing lack of longitudinal histopathological and biomechanical data for human arteries in health and disease highlights the importance of studying the many genetic, pharmacological, and surgical models that are available in mice. As a result, there has been a significant increase in the number of reports on the biomechanics of murine arteries over the past decade, particularly for the common carotid artery. Whereas most of these studies have focused on wild-type controls or comparing controls vs. a single model of altered hemodynamics or vascular disease, there is a pressing need to compare results across many different models to understand more broadly the effects of genetic mutations, pharmacological treatments, or surgical alterations on the evolving hemodynamics and the microstructure and biomechanical properties of these vessels. This paper represents a first step toward this goal, that is, a biomechanical phenotyping of common carotid arteries from control mice and seven different mouse models that represent alterations in elastic fiber integrity, collagen remodeling, and smooth muscle cell functionality.

Appendix

Reported values of systolic blood pressure summarized in Table 1 were collected using different methods, with data for control, Ang-II ApoE ^−/−, and Acta2 ^−/− mice measured using a noninvasive tail cuff method in the conscious mouse,3,24,45 data for the Fbn1 ^mgR/mgR and Fbln5 ^−/− mice measured via an indwelling polyethylene catheter in the conscious mouse,37,54 and data for the mdx and Sgcd ^−/− mice measured under isoflurane anesthesia using a left ventricular catheter.47 To render more consistent the comparison of intramural stress, stiffness, and stored energy across mouse models, these pressures were adjusted to central arterial pressure in the conscious state using published correlations.34,52 Briefly, Whitesall and colleagues simultaneously measured pressure using direct (radiotelemetry) and indirect (noninvasive tail-cuff) methods and reported a linear relationship, P _TC = 0.961 × P _C + 4.203 mmHg, where P _TC and P _C are systolic pressures measured by tail-cuff and telemetry (or central pressure), respectively. Rearranging this equation, tail-cuff measured pressures (i.e., control, Ang-II ApoE ^−/−, and Acta2 ^−/− mice) were adjusted to the conscious central pressure state. In contrast, Janssen and colleagues used an indwelling central artery catheter to evaluate effects of multiple anesthetics on the hemodynamics in mice. They found that isoflurane reduces the measured pressure by 24.3% relative to conscious ambulatory pressures. Hence, we adjusted pressures measured under isoflurane anesthesia (i.e., mdx and Sgcd ^−/−) via P _A = 0.757 × P _C, where P _A represents the anesthetized pressure. Table 1 thus lists both the value reported in the respective paper and the values adjusted herein.