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Ultrasound Induces Similar Temporal Endothelial Expression Patterns of eNOS and KLF2 as Normal Flow.

Jaideep Sahni1, Ian S McCue1, Adam R Johnson1

  • 1Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, USA.

Ultrasound in Medicine & Biology
|September 21, 2024
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Summary

Longer low-intensity pulsed ultrasound (LIPUS) exposure enhanced endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 2 (KLF2) gene expression. Six hours of LIPUS maximized beneficial gene expression, similar to normal flow but with faster response.

Keywords:
Acoustic pressureAtherosclerosisBiomechanicsEndothelial cellsLow-intensity pulsed ultrasoundShear stressWound healing

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Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Mechanobiology

Background:

  • Vascular endothelial cells respond to mechanical stimuli.
  • Low-intensity pulsed ultrasound (LIPUS) is a therapeutic modality.
  • Understanding LIPUS effects on endothelial gene expression is crucial for therapeutic applications.

Purpose of the Study:

  • To investigate the sensitivity of vascular endothelial cells to prolonged low-intensity pulsed ultrasound (LIPUS) exposure.
  • To compare LIPUS effects with normal blood flow on gene expression.
  • To identify the optimal LIPUS duration for maximizing mechanosensitive gene expression.

Main Methods:

  • Human umbilical vein endothelial cells were exposed to LIPUS (1 MHz, 217 kPa) for varying durations (20 min to 24 h).
  • Gene expression of endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 2 (KLF2) was quantified using RT-qPCR.
  • Cells exposed to normal flow served as a comparator.

Main Results:

  • Maximum eNOS and KLF2 expression was observed at 6 hours of LIPUS exposure.
  • LIPUS induced a faster beneficial response compared to normal flow, though flow resulted in higher overall gene expression.
  • Gene expression patterns under LIPUS and normal flow were qualitatively similar.

Conclusions:

  • Extended LIPUS exposure can enhance the expression of beneficial endothelial genes.
  • LIPUS and normal flow appear to activate similar cellular signaling pathways.
  • Increased RNA yield with LIPUS may indicate a wound-healing rather than atheroprotective response.