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

Abstract

Clinical assessment of arterial stiffness relies on noninvasive measurements of regional pulse wave velocity or local distensibility. However, arterial stiffness measures do not discriminate underlying changes in arterial wall constituent properties (e.g., in collagen, elastin, or smooth muscle), which is highly relevant for development and monitoring of treatment. In arterial stiffness in recent clinical-epidemiological studies, we systematically review clinical-epidemiological studies (2012–) that interpreted arterial stiffness changes in terms of changes in arterial wall constituent properties (63 studies included of 514 studies found). Most studies that did so were association studies (52 of 63 studies) providing limited causal evidence. Intervention studies (11 of 63 studies) addressed changes in arterial stiffness through the modulation of extracellular matrix integrity (5 of 11 studies) or smooth muscle tone (6 of 11 studies). A handful of studies (3 of 63 studies) used mathematical modeling to discriminate between extracellular matrix components. Overall, there exists a notable gap in the mechanistic interpretation of stiffness findings. In constitutive model-based interpretation, we first introduce constitutive-based modeling and use it to illustrate the relationship between constituent properties and stiffness measurements (“forward” approach). We then review all literature on modeling approaches for the constitutive interpretation of clinical arterial stiffness data (“inverse” approach), which are aimed at estimation of constitutive properties from arterial stiffness measurements to benefit treatment development and monitoring. Importantly, any modeling approach requires a tradeoff between model complexity and measurable data. Therefore, the feasibility of changing in vivo the biaxial mechanics and/or vascular smooth muscle tone should be explored. The effectiveness of modeling approaches should be confirmed using uncertainty quantification and sensitivity analysis. Taken together, constitutive modeling can significantly improve clinical interpretation of arterial stiffness findings.

The Role of Vascular Smooth Muscle Cells in Arterial Remodeling: Focus on Calcification-Related Processes

“…The capacity of the vessel wall to elastically distend is important to accommodate the volume ejected with each heartbeat and to limit peripheral pressure pulsations. The active tone and spatial arrangement of VSMCs may influence the mechanical load on the ECM components and, therefore, modulate vessel diameter and stiffness [18]. Chronic exposure to high blood pressure increases tensile stress [9] to which VSMCs respond by proliferation, resulting in hyperplasia and thickening of the vascular wall.…”

“…To remodel the ECM, synthetic VSMCs produce metalloproteinases (MMPs), such as collagenases and elastases, that allow them to migrate to sites of injury [15,16,17]. VSMC-mediated remodeling of ECM within the vessel wall may result in increased arterial stiffness [13,18], contributing to systolic hypertension and altered hemodynamic conditions in end-organs such as the brain, kidneys and heart [19].…”

Blackcurrant (Ribes nigrum L.) Extract Exerts Potential Vasculoprotective Effects in Ovariectomized Rats, Including Prevention of Elastin Degradation and Pathological Vascular Remodeling

“…Additionally, estrogen promotes an elastic matrix profile, which is likely to influence large artery stiffness [21]. Furthermore, vascular remodeling can lead to various pathological vascular disorders, such as hypertension, atherosclerosis, and lower-extremity venous disease [22][23][24][25][26]. Phytoestrogens are assumed to improve menopausal symptoms; however, their effects on vascular diseases such as atherosclerosis remain unclear [1].…”

A Constrained Mixture Theory Model to Study Autoregulation in the Coronary Circulation

“…Constrained mixture theory models have been widely applied to describe the nonlinear mechanical behavior of arterial tissue, accounting for the contributions of the main load-bearing constituents (e.g., collagen, elastin and SMCs) (26, 74). This theory provides a formal means to represent mechanical function of a vessel based on the properties of its constituents and the relative mass fractions of those constituents in the composition of the vessel wall.…”