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Review
. 2014 Aug;18(8):1491-508.
doi: 10.1111/jcmm.12164. Epub 2013 Nov 17.

A systems biology view of blood vessel growth and remodelling

Elizabeth A Logsdon  1 , Stacey D Finley, Aleksander S Popel, Feilim Mac Gabhann
Affiliations
Review

A systems biology view of blood vessel growth and remodelling

Elizabeth A Logsdon et al. J Cell Mol Med. 2014 Aug.

Abstract

Blood travels throughout the body in an extensive network of vessels - arteries, veins and capillaries. This vascular network is not static, but instead dynamically remodels in response to stimuli from cells in the nearby tissue. In particular, the smallest vessels - arterioles, venules and capillaries - can be extended, expanded or pruned, in response to exercise, ischaemic events, pharmacological interventions, or other physiological and pathophysiological events. In this review, we describe the multi-step morphogenic process of angiogenesis - the sprouting of new blood vessels - and the stability of vascular networks in vivo. In particular, we review the known interactions between endothelial cells and the various blood cells and plasma components they convey. We describe progress that has been made in applying computational modelling, quantitative biology and high-throughput experimentation to the angiogenesis process.

Keywords: angiogenesis; computational model; mathematical model; multi-scale modelling; systems biology.

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Figures

Fig. 1
Fig. 1
Timeline of the angiogenesis process. Angiogenesis is a morphogenesis process that consists of several discrete steps: (1) angiogenic stimulus, (2) endothelial sprouting, (3) vascular branching and elongation, (4) lumen formation and anastomosis and (5) vessel maturation. These concerted steps involve a plethora of molecular signals (Fig. 2) that carry communication between different cell types in the microenvironment, ultimately giving rise to a new blood vessel. Although sprouting angiogenesis has been studied most widely, there are other modes of angiogenesis including intussusception and vessel splitting.
Fig. 2
Fig. 2
Promoters and inhibitors of angiogenesis. A balance of pro- and anti-angiogenic factors maintains homeostasis [135]. In diseases characterized by hypervascularization such as cancer and age-related macular degeneration, the balance is disrupted to promote angiogenesis. Increased expression of inhibitors of angiogenesis is a hallmark of ischaemic diseases such as coronary and peripheral arterial disease. The figure shows a short list of protein families important to the angiogenic balance, but is not exhaustive [198] and new angiogenesis modulators continue to be discovered. Many therapeutics targeting the factors named above are either already FDA-approved or are in clinical trials (see text).
Fig. 3
Fig. 3
Published computational models of angiogenesis. Models of angiogenesis are collated by model type, the approximate stages of angiogenesis simulated in the models are indicated in grey and the publication years are noted. This figure displays an at-a-glance view of systems biology efforts in modelling angiogenesis.
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