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Impact of spatial and temporal stability of flow vortices on vascular endothelial cells

Biomechanics and Modeling in Mechanobiology volume 22, pages 71–83 (2023)Cite this article

Abstract

Purpose: Intracranial aneurysms (IAs) are pathological dilations of cerebrovascular vessels due to degeneration of the mechanical strength of the arterial wall, precluded by altered cellular functionality. The presence of swirling hemodynamic flow (vortices) is known to alter vascular endothelial cell (EC) morphology and protein expression indicative of IAs. Unfortunately, less is known if vortices with varied spatial and temporal stability lead to differing levels of EC change. The aim of this work is to investigate vortices of varying spatial and temporal stability impact on ECs. Methods: Vortex and EC interplay was investigated by a novel combination of parallel plate flow chamber (PPFC) design and computational analysis. ECs were exposed to laminar (7.5 dynes/\(\hbox {cm}^2\) wall shear stress) or low (<1 dynes/\(\hbox {cm}^2\)) stress vortical flow using PPFCs. Immunofluorescent imaging analyzed EC morphology, while ELISA tests quantified VE-cadherin (cell-cell adhesion), VCAM-1 (macrophage-EC adhesion), and cleaved caspase-3 (apoptotic signal) expression. PPFC flow was simulated, and vortex stability was calculated via the temporally averaged degree of (volume) overlap (TA-DVO) of vortices within a given area. Results: EC morphological changes were independent of vortex stability. Increased stability promoted VE-cadherin degradation (correlation coefficient r = \(-\)0.84) and 5-fold increased cleaved caspase-3 post 24 h in stable (TA-DVO 0.736 ± 0.05) vs unstable (TA-DVO 0.606 \(\pm \,\)0.2) vortices. ECs in stable vortices displayed a 4.5-fold VCAM-1 increase than unstable counterparts after 12 h. Conclusion: This work demonstrates highly stable disturbed flow imparts increased inflammatory signaling, degraded cell-cell adhesion, and increased cellular apoptosis than unstable vortices. Such knowledge offers novel insight toward understanding IA development and rupture.

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Acknowledgements

This study was supported by the National Institutes of Health (1R01HL146652-01A1, and 1R15HL145654-01 to FZ and 1R01EB029570-01A1 to JJ). It was also funded by American Heart Association (18PRE33990321) to KS.

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  1. Wenkai Jia and Weilue He contributed equally to this study.

Authors and Affiliations

  1. Biomedical Engineering, Michigan Technological University, 1400 Townsend Drive, Houghton, MI, 49931, USA

    Kevin Sunderland, Weilue He & Jingfeng Jiang

  2. Biomedical Engineering, Texas A &M University, 400 Bizzell St, College Station, TX, 77843, USA

    Wenkai Jia & Feng Zhao

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  1. Kevin Sunderland
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Correspondence to Jingfeng Jiang or Feng Zhao.

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Appendices

A Computational fluid dynamic simulation

Fig. 6
figure 6

Example of meshed 3D structures used in simulations. a Laminar chamber, b Disturbed chamber. Only a portion of the structures are shown to assist in visualizing the mesh

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Fig. 7
figure 7

Volumetric flow waveforms generated by the peristaltic pump in this work. User-defined functions were used to recreate these waveforms for CFD simulation inflow boundary conditions. The waveform for the pulsatile laminar flow (red) had an averaged volumetric flow rate of 0.667 ml/second (40 ml/min) while the waveform for the disturbed flow (blue) was 0.441 ml/second (26.5 ml/min)

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B Experimental setup

Fig. 8
figure 8

Setup of the chamber. A Masterflex L/S peristaltic pump (Cole-Parmer, Vernon Hills IL, USA), cell culture medium reservoir (red circle), 2nm pore filter for gas exchange (white arrow), flow chamber (blue square) with inserted PDMS baffles (green arrows), and silicone washer (yellow arrow). 3-way stopcocks pre- and post-chamber for bubble removal. Laminar flow experiments had a similar setup, with the laminar flow chamber having no PDMS baffles

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C Morphological measurements

Fig. 9
figure 9

Example showing example measured axes for a Angle (red line) for Feret’s diameter in relation to the x-axis of the image, and b Long axis (red line) and short axis (black line) measured for nuclei aspect ratio

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Sunderland, K., Jia, W., He, W. et al. Impact of spatial and temporal stability of flow vortices on vascular endothelial cells. Biomech Model Mechanobiol 22, 71–83 (2023). https://doi.org/10.1007/s10237-022-01632-y

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  • DOI: https://doi.org/10.1007/s10237-022-01632-y

Keywords

  • Endothelial cells
  • Swirling flow
  • Aneurysm
  • Aneurysmal flow

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