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Abstract: SA-PO560

A Bypass Flow Model to Study Endothelial Cell Mechanotransduction across Diverse Flow Environments

Session Information

  • Bioengineering
    October 26, 2024 | Location: Exhibit Hall, Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Bioengineering

  • 400 Bioengineering

Authors

  • Xiao, Zhuotao, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Postma, Rudmer J., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Van Zonneveld, Anton Jan, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • van den Berg, Bernard, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Sol, Wendy Margaritha Petronella Jannetje, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • White, Nicholas, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Mirza, Asad M., Florida International University, Miami, Florida, United States
  • Wen, Jun, Southwest University of Science and Technology, Mianyang, Sichuan, China
  • Bijkerk, Roel, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Rotmans, Joris I., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
Background

Disturbed flow is one of the pathological initiators of endothelial dysfunction in intimal hyperplasia (IH) which is commonly seen in vascular bypass grafts, and arteriovenous fistulas. Various in vitro disease models have been designed to simulate the hemodynamic conditions found in the vasculature. Nonetheless, prior investigations have encountered challenges in establishing a robust disturbed flow model. In the present study, we aim to address this gap by introducing an in vitro bypass flow model capable of inducing disturbed flow and other hemodynamics patterns through a pulsatile flow in the same model, Fig. A.

Methods

We employed computational fluid dynamics (CFD) to simulate hemodynamics and compared the morphology and functions of human umbilical venous endothelial cells (HUVECs) under disturbed flow conditions to those in physiological flow or stagnant conditions.

Results

CFD analysis revealed the generation of disturbed flow within the model, pinpointing the specific location in the channel where the effects of disturbed flow were observed, Fig. B. High-content screening, a single-cell morphological profile assessment, demonstrated that HUVECs in the disturbed flow area exhibited random orientation, and morphological features were significantly distinct compared to cells in the physiological flow or stagnant condition after a two days of flow exposure, Fig. C D. HUVECs exposed to disturbed flow underwent extensive remodeling of the adherens junctions and expressed higher levels of endothelial cell activation markers compared to other hemodynamic conditions.

Conclusion

In conclusion, our in vitro bypass flow model provides a robust platform for investigating the associations between disturbed flow pattern and vascular diseases.

Funding

  • Private Foundation Support