Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries

Abstract

The impact of disease-related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared with frequently used rodent mesenteric arteries. We hypothesized that the biaxial mechanics of PRA mirror pressure-induced changes in the ECM microarchitecture. This was tested using isolated pig PRA as a model system, integrating vital imaging, pressure myography, and mathematical modeling. Collagenase and elastase digestions were applied to evaluate the load-bearing roles of collagen and elastin, respectively. The incremental elastic modulus linearly related to the straightness of adventitial collagen fibers circumferentially and longitudinally (both ≥ 0.99), whereas there was a nonlinear relationship to the internal elastic lamina elastin fiber branching angles. Mathematical modeling suggested a collagen recruitment strain (means ± SE) of 1.1 ± 0.2 circumferentially and 0.20 ± 0.01 longitudinally, corresponding to a pressure of ~40 mmHg, a finding supported by the vital imaging. The integrated method was tested on human PRA to confirm its validity. These showed limited circumferential distensibility and elongation and a collagen recruitment strain of 0.8 ± 0.1 circumferentially and 0.06 ± 0.02 longitudinally, reached at a distending pressure below 20 mmHg. This was confirmed by vital imaging showing negligible microarchitectural changes of elastin and collagen upon pressurization. In conclusion, we show here, for the first time in resistance arteries, a quantitative relationship between pressure-induced changes in the extracellular matrix and the arterial wall mechanics. The strength of the integrated methods invites for future detailed studies of microvascular pathologies. This is the first study to quantitatively relate pressure-induced microstructural changes in resistance arteries to the mechanics of their wall. Principal findings using a pig model system were confirmed in human arteries. The combined methods provide a strong tool for future hypothesis-driven studies of microvascular pathologies.

Constitutive interpretation of arterial stiffness in clinical studies: a methodological review

“…We submit that the consequent lack of quantitative mechanistic insight limits the field in designing and testing treatment approaches to target the ultrastructural basis of arterial stiffening (15,37,140,159). Motivated by previous work of ours and others (13,23,39,125,142,151), we consider the skillful application of constitutive models to clinical arterial stiffness data of great potential value to close the mentioned gap. Therefore, in the next section, we will discuss the applicability of constitutive modeling and provide some guidance on releasing its potential.…”

Biomimetic human small muscular pulmonary arteries

“…Figure 2A Figure 2B demonstrates the design space for the flexural stiffness  of tubular structures with thickness varying from 0.5 to 2 m and Young's modulus varying from 1 to 200 GPa. For in vivo hSMPA, thicknesses of 10 to 30 m and Young's moduli of 15 to 500 kPa have been reported in the literature (40)(41)(42)(43). The inserted plane in Fig.…”

Assessing Collagen and Elastin Pressure-dependent Microarchitectures in Live, Human Resistance Arteries by Label-free Fluorescence Microscopy

“…For smaller arteries of any species (e.g., human pericardial 13 , pulmonary 14 and subcutaneous 15 arteries, rat mesenteric arteries 16,17,18,19,20 , mouse cremaster, mesenteric, cerebral, femoral and carotid arteries 21,22,23,24,25,26,27 ) imaging of the entire wall thickness is possible and can be combined with mechanical testing. This allows simultaneous recording of the mechanical properties and the structural arrangements within the wall.…”

“…This allows simultaneous recording of the mechanical properties and the structural arrangements within the wall. However, a direct mathematical modeling of the relationship between the observed alterations in the three-dimensional structure of the ECM and changed mechanical properties of the resistance arterial wall, has to the best of our knowledge only been reported upon recently in human resistance arteries 13,15 .…”