Structural adaptation of microvascular networks: functional roles of adaptive responses

Pries, Axel R.; Reglin, Bettina; Secomb, Timothy W.

doi:10.1152/ajpheart.2001.281.3.h1015

Cited by 150 publications

(208 citation statements)

References 48 publications

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“…This integration process, called remodeling, is driven by metabolic signals such as local hypoxia (Pfeifer et al, 1998) as well as mechanical forces of the flowing blood (Bongrazio et al, 2000;Pries et al, 2001). These stimuli are acting not only locally but are transferred upstream over the entire vascular network (Dora, 2001;Pries et al, 2001). Model calculations have shown that metabolic signals such as the local PO 2 and mechanical forces such as shear stress are essential for the maintenance of the capillary network structure as well as for the adaptation to an altered metabolic situation or to occlusions of pathways within the network (Pries and Secomb, 2000).…”

mentioning

confidence: 99%

Massive Inborn Angiogenesis in the Brain Scarcely Raises Cerebral Blood Flow

Vogel

Gehrig

Kuschinsky

et al. 2004

J Cereb Blood Flow Metab

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Summary:The functional consequences of increased capillary densities in the brain resulting from vascular endothelial growth factor (VEGF 165 ) overexpression are unknown. Therefore, the authors measured local CBF using the iodo-[ 14 C]antipyrine technique in transgenic mice expressing brain-specifically sixfold higher VEGF 165 levels and in nontransgenic littermates. To reveal possible compensatory vasoconstriction, CBF was also measured during severe hypercapnia (PaCO 2 > 130 mm Hg). Simultaneously, local capillary density, perfusion state, and blood-brain-barrier permeability were assessed. Using the 2-[ 14 C]deoxyglucose method, metabolic effects of VEGF overexpression could be excluded. In transgenic mice all capillaries showed normal morphology and a tight blood-brain barrier. However, 3% nonperfused capillaries in some brain structures indicate ongoing angiogenesis. Capillary density was drastically increased in transgenic mice in white matter structures (70% to 185%), the dentate gyrus (143%), and caudate nucleus (86%). In all other brain structures investigated, capillary densities were moderately increased by approximately 20%. Normocapnic CBF did not differ between transgenic and nontransgenic mice. During maximal hypercapnic vasodilation, CBF was 20% to 30% higher in transgenic mice, although only in brain structures where capillary density was increased more than twofold. These findings suggest that attenuated CBF in transgenic mice during normocapnia is only partly due to a compensatory vasoconstriction, and that microvascular networks in transgenic brains might be ineffectively constructed.

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mentioning

confidence: 99%

Massive Inborn Angiogenesis in the Brain Scarcely Raises Cerebral Blood Flow

Vogel

Gehrig

Kuschinsky

et al. 2004

J Cereb Blood Flow Metab

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“…In this paper, vessel adaptation follows the treatment of [35,36,37,38] Pries et al (1995, 1998, 2001a). The model considers a number of stimuli affecting vessel diameter that account for the influence of the wall shear stress (S wss ), the intravascular pressure (S p ), and a metabolic mechanism depending on the blood haematocrit (S m ).…”

Section: Vessel Adaptationmentioning

confidence: 99%

“…and τ ref is a constant included to avoid singular behaviour at low shear rates [37] (Pries 2001a). Stresses in (B4) and (B5) are in dynes/cm 2 .…”

Section: Vessel Adaptationmentioning

confidence: 99%

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

McDougall¹,

Chaplain

Stephanou³

et al. 2010

Math. Model. Nat. Phenom.

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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 * Corresponding author. E-mail: chaplain@maths.dundee.ac. Impact of pericytes on blood vessel Networks which a given VDA would be most effective.

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“…Pries and co-workers [39]- [41] have developed models of structural adaptation of microvasculature in response to blood flow. They provide a phenomenological model of blood viscosity as a function of vessel radius and haematocrit (volume fraction of red blood cells, which constitute the majority of the solid phase of the blood).…”

Section: Models Of Tumour Angiogenesismentioning

confidence: 99%

Mathematical Modelling of Tumour Dormancy

Page¹

2009

Math. Model. Nat. Phenom.

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Abstract. Many tumours undergo periods in which they apparently do not grow but remain at a roughly constant size for extended periods. This is termed tumour dormancy. The mechanisms responsible for dormancy include failure to develop an internal blood supply, individual tumour cells exiting the cell cycle and a balance between the tumour and the immune response to it. Tumour dormancy is of considerable importance in the natural history of cancer. In many cancers, and in particular in breast cancer, recurrence can occur many years after surgery to remove the primary tumour, following a long period of occult disease. Mathematical modelling suggested that continuous growth of tumours was incompatible with data of the times of recurrence in breast cancer, suggesting that tumour dormancy was a common phenomenon. Modelling has also been applied to understanding the mechanisms responsible for dormancy, how they can be manipulated and the implications for cancer therapy. Here, the literature on mathematical modelling of tumour dormancy is reviewed. In conclusion, promising future directions for research are discussed.

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Structural adaptation of microvascular networks: functional roles of adaptive responses

Cited by 150 publications

References 48 publications

Massive Inborn Angiogenesis in the Brain Scarcely Raises Cerebral Blood Flow

Massive Inborn Angiogenesis in the Brain Scarcely Raises Cerebral Blood Flow

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

Mathematical Modelling of Tumour Dormancy

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