Proteoglycans and vascular residual stress: exposing a hidden mechanism for regulating blood vessel biomechanics

Vikrum Thimmappa, Department of Biomedical Engineering, Columbia University, New York, NY 10027, U Evren U. Azeloglu, Department of Biomedical Engineering, Columbia University, New York, NY 10027, U Gerard A. Ateshian, Department of Biomedical Engineering, Columbia University, New York, NY 10027, U Kevin D. Costa, Department of Biomedical Engineering, Columbia University, New York, NY 10027, U

Abstract Biomechanics plays a fundamental role in understanding how blood vessels function in the body, and how they adapt in response to abnormal loading conditions that accompany many devastating cardiovascular diseases. In particular, blood vessels contain so-called “residual stresses” that remain within the vessel wall even when all external loads have been removed. Residual stresses function to optimize the physiologic mechanical state of cells residing within the vascular wall. Despite this essential functional role, the mechanisms governing the origin and adaptation of vascular residual stress remain poorly understood. Our group recently demonstrated that residual stresses can arise from large, negatively charged proteoglycan molecules located preferentially in the inner layers of the vessel wall. The present study further tests this mechanism by examining the relationship between proteoglycan heterogeneity and regional variations in residual stress at different anatomical locations in rat arteries. Residual stress due to proteoglycan effects was quantified by computing a Donnan opening angle (ϑD) from measurements of cut arterial rings immersed in solutions with specific ionic concentrations, and this was correlated with an index of proteoglycan heterogeneity (HP) obtained by quantitative histological analysis of the vessel wall. ϑD exhibited a second order polynomial dependence on HP (R2=0.724, p = 0.011) with a maximum opening angle at HP = 48%, consistent with the theoretically predicted value of 50%. These findings support our hypothesis relating proteoglycans and vascular residual stress, suggesting a novel mechanism by which vascular cells may regulate blood vessel biomechanics by modification of proteoglycan content in arterial walls.

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