Early Atherosclerotic Changes in Coronary Arteries are Associated with Endothelium Shear Stress Contraction/Expansion Variability

Valentina Mazzi,Umberto Morbiducci,Karol Calò,Giuseppe De Nisco,Jolanda J Wentzel,Claudio Chiastra,David A Steinman,Ayla Hoogendoorn,Diego Gallo

doi:10.1007/s10439-021-02829-5

Abstract

Although unphysiological wall shear stress (WSS) has become the consensus hemodynamic mechanism for coronary atherosclerosis, the complex biomechanical stimulus affecting atherosclerosis evolution is still undetermined. This has motivated the interest on the contraction/expansion action exerted by WSS on the endothelium, obtained through the WSS topological skeleton analysis. This study tests the ability of this WSS feature, alone or combined with WSS magnitude, to predict coronary wall thickness (WT) longitudinal changes. Nine coronary arteries of hypercholesterolemic minipigs underwent imaging with local WT measurement at three time points: baseline (T1), after 5.6 ± 0.9 (T2), and 7.6 ± 2.5 (T3) months. Individualized computational hemodynamic simulations were performed at T1 and T2. The variability of the WSS contraction/expansion action along the cardiac cycle was quantified using the WSS topological shear variation index (TSVI). Alone or combined, high TSVI and low WSS significantly co-localized with high WT at the same time points and were significant predictors of thickening at later time points. TSVI and WSS magnitude values in a physiological range appeared to play an atheroprotective role. Both the variability of the WSS contraction/expansion action and WSS magnitude, accounting for different hemodynamic effects on the endothelium, (1) are linked to WT changes and (2) concur to identify WSS features leading to coronary atherosclerosis.

Highlights

Among the biomechanical factors, local hemodynamics is a recognized promoter of the initiation and progression of atherosclerotic disease in coronary arteries.[4,36,47] A large body of literature has supported the consistency of the ‘hemodynamic risk hypothesis’ in coronary disease, emphasizing the crucial and multifaceted role played by wall shear stress (WSS) in conditioning the initiation, localization, and growth of coronary lesions.[4]
It is expected that the overall structure of the WSS topological skeleton does not markedly change its spatial configuration in the time interval T2T1, as the number and nature of fixed points affect the pattern of manifolds onto the luminal surface
The most striking results to emerge from this study are that: (1) both investigated hemodynamic stimuli at the endothelial level—high variations in the WSS contraction/expansion action on the endothelium along the cardiac cycle and low time-average WSS magnitude—were associated with wall thickness (WT) growth, accounting for different hemodynamic effects portending atherosclerosis; (2) topological shear variation index (TSVI) and time-averaged wall shear stress (TAWSS) values in a physiological range appeared to play an atheroprotective role on endothelial cells (ECs); (3) high variations in WSS manifolds dynamics along the cardiac cycle corresponded to intravascular regions of separation between left- and right-handed helical flow patterns

Summary

Introduction

Local hemodynamics is a recognized promoter of the initiation and progression of atherosclerotic disease in coronary arteries.[4,36,47] A large body of literature has supported the consistency of the ‘hemodynamic risk hypothesis’ in coronary disease, emphasizing the crucial and multifaceted role played by wall shear stress (WSS) in conditioning the initiation, localization, and growth of coronary lesions.[4].

Methods

Results

Discussion

Conclusion