Modelling the Impact of Pericyte Migration and Coverage of Vessels on the Efficacy of Vascular Disrupting Agents

S. R. McDougall; M. A.J. Chaplain; A. Stéphanou; A. R.A. Anderson

Mathematical Modelling of Natural Phenomena (2010)

  • Volume: 5, Issue: 1, page 163-202
  • ISSN: 0973-5348

Abstract

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Over the past decade or so, there have been a large number of modelling approaches aimed at elucidating the most important mechanisms affecting the formation of new capillaries from parent blood vessels — a process known as angiogenesis. Most studies have focussed upon the way in which capillary sprouts are initiated and migrate in response to diffusible chemical stimuli supplied by hypoxic stromal cells and leukocytes in the contexts of solid tumour growth and wound healing. However, relatively few studies have examined the important role played by blood perfusion during angiogenesis and fewer still have explored the ways in which a dynamically evolving vascular bed architecture can affect the distribution of flow within it. From the perspective of solid tumour growth and, perhaps more importantly, its treatment (e.g. chemotherapy), it would clearly be of some benefit to understand this coupling between vascular structure and perfusion more fully. This paper focuses on the implications of such a coupling upon chemotherapeutic, anti-angiogenic, and anti-vascular treatments.In an extension to previous work by the authors, the issue of pericyte recruitment during vessel maturation is considered in order to study the effects of different anti-vascular and anti-angiogenic therapies from a more rigorous modelling standpoint. Pericytes are a prime target for new vascular disrupting agents (VDAs) currently in clinical trials. However, different compounds attack different components of the vascular network and the implications of targeting only certain elements of the capillary bed are not immediately clear. In light of these uncertainties, the effects of anti-angiogenic and anti-vascular drugs are re-examined by using an extended model that includes an interdependency between vessel remodelling potential and local pericyte density. Two- and three-dimensional simulation results are presented and suggest that it may be possible to identify a VDA-specific “plasticity window” (a time period corresponding to low pericyte density), within which a given VDA would be most effective.

How to cite

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McDougall, S. R., et al. "Modelling the Impact of Pericyte Migration and Coverage of Vessels on the Efficacy of Vascular Disrupting Agents." Mathematical Modelling of Natural Phenomena 5.1 (2010): 163-202. <http://eudml.org/doc/197629>.

@article{McDougall2010,
abstract = {Over the past decade or so, there have been a large number of modelling approaches aimed at elucidating the most important mechanisms affecting the formation of new capillaries from parent blood vessels — a process known as angiogenesis. Most studies have focussed upon the way in which capillary sprouts are initiated and migrate in response to diffusible chemical stimuli supplied by hypoxic stromal cells and leukocytes in the contexts of solid tumour growth and wound healing. However, relatively few studies have examined the important role played by blood perfusion during angiogenesis and fewer still have explored the ways in which a dynamically evolving vascular bed architecture can affect the distribution of flow within it. From the perspective of solid tumour growth and, perhaps more importantly, its treatment (e.g. chemotherapy), it would clearly be of some benefit to understand this coupling between vascular structure and perfusion more fully. This paper focuses on the implications of such a coupling upon chemotherapeutic, anti-angiogenic, and anti-vascular treatments.In an extension to previous work by the authors, the issue of pericyte recruitment during vessel maturation is considered in order to study the effects of different anti-vascular and anti-angiogenic therapies from a more rigorous modelling standpoint. Pericytes are a prime target for new vascular disrupting agents (VDAs) currently in clinical trials. However, different compounds attack different components of the vascular network and the implications of targeting only certain elements of the capillary bed are not immediately clear. In light of these uncertainties, the effects of anti-angiogenic and anti-vascular drugs are re-examined by using an extended model that includes an interdependency between vessel remodelling potential and local pericyte density. Two- and three-dimensional simulation results are presented and suggest that it may be possible to identify a VDA-specific “plasticity window” (a time period corresponding to low pericyte density), within which a given VDA would be most effective.},
author = {McDougall, S. R., Chaplain, M. A.J., Stéphanou, A., Anderson, A. R.A.},
journal = {Mathematical Modelling of Natural Phenomena},
keywords = {tumour-induced angiogenesis; blood vessel networks; pericytes; chemotherapeutic; anti-angiogenic; anti-vascular treatment protocols},
language = {eng},
month = {2},
number = {1},
pages = {163-202},
publisher = {EDP Sciences},
title = {Modelling the Impact of Pericyte Migration and Coverage of Vessels on the Efficacy of Vascular Disrupting Agents},
url = {http://eudml.org/doc/197629},
volume = {5},
year = {2010},
}

TY - JOUR
AU - McDougall, S. R.
AU - Chaplain, M. A.J.
AU - Stéphanou, A.
AU - Anderson, A. R.A.
TI - Modelling the Impact of Pericyte Migration and Coverage of Vessels on the Efficacy of Vascular Disrupting Agents
JO - Mathematical Modelling of Natural Phenomena
DA - 2010/2//
PB - EDP Sciences
VL - 5
IS - 1
SP - 163
EP - 202
AB - Over the past decade or so, there have been a large number of modelling approaches aimed at elucidating the most important mechanisms affecting the formation of new capillaries from parent blood vessels — a process known as angiogenesis. Most studies have focussed upon the way in which capillary sprouts are initiated and migrate in response to diffusible chemical stimuli supplied by hypoxic stromal cells and leukocytes in the contexts of solid tumour growth and wound healing. However, relatively few studies have examined the important role played by blood perfusion during angiogenesis and fewer still have explored the ways in which a dynamically evolving vascular bed architecture can affect the distribution of flow within it. From the perspective of solid tumour growth and, perhaps more importantly, its treatment (e.g. chemotherapy), it would clearly be of some benefit to understand this coupling between vascular structure and perfusion more fully. This paper focuses on the implications of such a coupling upon chemotherapeutic, anti-angiogenic, and anti-vascular treatments.In an extension to previous work by the authors, the issue of pericyte recruitment during vessel maturation is considered in order to study the effects of different anti-vascular and anti-angiogenic therapies from a more rigorous modelling standpoint. Pericytes are a prime target for new vascular disrupting agents (VDAs) currently in clinical trials. However, different compounds attack different components of the vascular network and the implications of targeting only certain elements of the capillary bed are not immediately clear. In light of these uncertainties, the effects of anti-angiogenic and anti-vascular drugs are re-examined by using an extended model that includes an interdependency between vessel remodelling potential and local pericyte density. Two- and three-dimensional simulation results are presented and suggest that it may be possible to identify a VDA-specific “plasticity window” (a time period corresponding to low pericyte density), within which a given VDA would be most effective.
LA - eng
KW - tumour-induced angiogenesis; blood vessel networks; pericytes; chemotherapeutic; anti-angiogenic; anti-vascular treatment protocols
UR - http://eudml.org/doc/197629
ER -

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