A systems biology view of blood vessel growth and remodelling

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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.

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Most cited references 195

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Angiogenesis in life, disease and medicine.

Peter Carmeliet (2005)

The growth of blood vessels (a process known as angiogenesis) is essential for organ growth and repair. An imbalance in this process contributes to numerous malignant, inflammatory, ischaemic, infectious and immune disorders. Recently, the first anti-angiogenic agents have been approved for the treatment of cancer and blindness. Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.

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Ranibizumab and bevacizumab for neovascular age-related macular degeneration.

Daniel Martin, Maureen Maguire, Gui-shuang Ying … (2011)

Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data. In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart. Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern. At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).

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A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer.

James Yang, Leah A. Haworth, Richard Sherry … (2003)

Mutations in the tumor-suppressor gene VHL cause oversecretion of vascular endothelial growth factor by clear-cell renal carcinomas. We conducted a clinical trial to evaluate bevacizumab, a neutralizing antibody against vascular endothelial growth factor, in patients with metastatic renal-cell carcinoma. A randomized, double-blind, phase 2 trial was conducted comparing placebo with bevacizumab at doses of 3 and 10 mg per kilogram of body weight, given every two weeks; the time to progression of disease and the response rate were primary end points. Crossover from placebo to antibody treatment was allowed, and survival was a secondary end point. Minimal toxic effects were seen, with hypertension and asymptomatic proteinuria predominating. The trial was stopped after the interim analysis met the criteria for early stopping. With 116 patients randomly assigned to treatment groups (40 to placebo, 37 to low-dose antibody, and 39 to high-dose antibody), there was a significant prolongation of the time to progression of disease in the high-dose--antibody group as compared with the placebo group (hazard ratio, 2.55; P 0.20 for all comparisons). Bevacizumab can significantly prolong the time to progression of disease in patients with metastatic renal-cell cancer. Copyright 2003 Massachusetts Medical Society

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Author and article information

Journal

Journal ID (nlm-ta): J Cell Mol Med

Journal ID (iso-abbrev): J. Cell. Mol. Med

Journal ID (publisher-id): jcmm

Title: Journal of Cellular and Molecular Medicine

Publisher: Blackwell Publishing Ltd (Oxford, UK )

ISSN (Print): 1582-1838

ISSN (Electronic): 1582-4934

Publication date (Print): August 2014

Publication date (Electronic): 17 November 2013

Volume: 18

Issue: 8

Pages: 1491-1508

Affiliations

[a ]Institute for Computational Medicine and Department of Biomedical Engineering, Johns Hopkins University Baltimore, MD, USA

[b ]Department of Biomedical Engineering, Johns Hopkins University School of Medicine Baltimore, MD, USA

Author notes

*Correspondence to: Feilim MAC GABHANN, Ph.D., Institute for Computational Medicine and Department of Biomedical Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA. Tel.: 410-516-4723 Fax: 410-516-5294 E-mail: feilim@ 123456jhu.edu

Article

DOI: 10.1111/jcmm.12164

PMC ID: 4190897

PubMed ID: 24237862

SO-VID: 19b73c84-c439-426b-8ceb-4dd43a29e0ef

License:

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

A systems biology view of blood vessel growth and remodelling

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Most cited references 195

Angiogenesis in life, disease and medicine.

Ranibizumab and bevacizumab for neovascular age-related macular degeneration.

A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer.

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