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The temporal basis of angiogenesis.

Katie Bentley1,2, Shilpa Chakravartula3

  • 1Computational Biology Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA kbentley@bidmc.harvard.edu.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|March 29, 2017
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Timing is crucial for blood vessel growth (angiogenesis). New research shows tissue conditions adapt cell behavior timing, influencing vascular network structure and offering new therapeutic targets.

Keywords:
active perceptionadaptationdynamicsmorphogenesistimevascular

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Area of Science:

  • Vascular Biology
  • Systems Biology
  • Morphodynamics

Background:

  • Angiogenesis, the growth of new blood vessels, is a dynamic process requiring precise coordination of multiple cell types.
  • The temporal dynamics of endothelial cell behavior are critical for forming functional vascular networks, yet remain understudied.
  • Existing research often overlooks the time-based properties influencing angiogenesis, despite timing's importance in other biological systems.

Purpose of the Study:

  • To present a novel, time-based model of endothelial cell behavior during angiogenesis.
  • To explore how tissue conditions modulate the timing of cellular decisions in vascular network formation.
  • To propose 'temporal adaptation' as a new framework for understanding vascular morphology and disease.

Main Methods:

  • Integrated computational (in silico) and experimental (in vivo) studies were employed.
  • Analysis focused on collective endothelial cell behaviors and decision-making processes.
  • Literature review contextualized findings within broader biological research on temporal regulation.

Main Results:

  • Tissue conditions can locally adapt the timing of endothelial cell behaviors to generate diverse vascular architectures.
  • Various factors, including semaphorins, VEGF, asymmetric cell division, and filopodia extension, act as temporal regulators.
  • These regulators modify the speed of cellular migration decisions, impacting network development.

Conclusions:

  • 'Temporal adaptation' offers a novel explanation for organ- and disease-specific vascular morphology.
  • 'Timing' emerges as a critical, yet previously elusive, factor in vascular biology.
  • Understanding temporal adaptation presents new therapeutic strategies targeting vascular development and disease.