A role for VEGF as a negative regulator of pericyte function and vessel maturation

Greenberg, Joshua I.; Shields, David J.; Barillas, Samuel; Acevedo, Lisette M.; Murphy, Eric A.; Huang, Jianhua; Scheppke, Lea; Stockmann, Christian; Johnson, Randall S.; Angle, Niren; Cheresh, David A.

doi:10.1038/nature07424

Cited by 555 publications

(491 citation statements)

References 26 publications

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“…Pericytes and VSM cells act as mural cells, tightly regulating the activity of endothelial cells [34]. Pericytes not only provide a vital structural support, these cells are central to the process of angiogenesis [19].…”

Section: Pericytes and Vascular Smooth Muscle Cellsmentioning

confidence: 99%

“…Angiogenesis describes the formation of blood vessels from pre-existing ones and occurs throughout life, during wound healing and is a requirement for normal organ development [34,44]. When new capillaries are required, pro-angiogenic mediators are increased which favours angiogenesis alongside decreased levels of angiogenic inhibitors.…”

Section: Angiogenic Processesmentioning

confidence: 99%

“…In a small study with bronchial biopsies, patients without glucocorticosteroid treatment showed more bronchial vascularisation, larger vessels and more VEGF receptors expressed in the tissue compared to COPD patients that were treated with inhaled glucocorticosteroids [119]. Interestingly, VEGF has been shown to act both as a promoter of endothelial cell function and a negative regulator of VSMCs and vessel maturation in combination with PDGF [34], highlighting the complex role of VEGF in vascular remodelling. The vascular changes in COPD patients seem to depend on VEGF as an important regulator in local and systemic inflammation and in interactions with TGF-β in regulation of ECM production [1].…”

Section: Vascular Changes and Growth Factors In Copdmentioning

confidence: 99%

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Pulmonary vascular changes in asthma and COPD

Harkness

Kanabar

Sharma

et al. 2014

Pulmonary Pharmacology & Therapeutics

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In chronic lung disorders such as in asthma and chronic obstructive pulmonary disease (COPD) there is increased bronchial angiogenesis and remodelling of pulmonary vessels culminating to altered bronchial and pulmonary circulation. The involvement of residential cells such as endothelial cells, smooth muscle cells and pulmonary fibroblasts, all appear to have a crucial role in the progression of vascular inflammation and remodelling. The regulatory abnormalities, growth factors and mediators implicated in the pulmonary vascular changes of asthma and COPD subjects and potential therapeutic targets have been described in this review.

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Section: Pericytes and Vascular Smooth Muscle Cellsmentioning

confidence: 99%

Section: Angiogenic Processesmentioning

confidence: 99%

Section: Vascular Changes and Growth Factors In Copdmentioning

confidence: 99%

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Pulmonary vascular changes in asthma and COPD

Harkness

Kanabar

Sharma

et al. 2014

Pulmonary Pharmacology & Therapeutics

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“…We then tested whether rapamycin and anti-VEGF antibody treatments also normalized the wall structure of the blood vessels (29,30), in particular the association of pericytes with tumor vessels. Therefore, we first determined the expression of alpha smooth muscle antigen (a-SMA), a marker for mature pericytes in control and treated tumors by using IHC (Fig.…”

Section: Antiangiogenesis Treatment Increased Pericyte Coverage Of Tumentioning

confidence: 99%

Time-Course Imaging of Therapeutic Functional Tumor Vascular Normalization by Antiangiogenic Agents

Zhang

Bindokas

Shen

et al. 2011

Molecular Cancer Therapeutics

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We describe here new technology that enables noninvasive imaging of therapeutic functional normalization of tumor blood vessels by antiangiogenic agents. Noninvasive variable-magnification in vivofluorescence imaging as well as fluorescence tomography was used to visualize functional vessel normalization. Changes in the same vessel before and after drug treatment were imaged with high resolution in real time. Differences in vascular responses to the mTOR inhibitor rapamycin and to an anti-VEGF antibody were functionally imaged. Tumor vessel normalization was shown by significantly reduced leakiness and subsequent improved tumor delivery of Paclitaxel-BODPY as well as by normalized morphology. The tumor vascular pool agent, AngioSense 750 , was retained only in tumors after either anti-VEGF antibody or rapamycin treatment, as visualized by noninvasive fluorescence tomography. The antiangiogenic therapy normalized vessels, which significantly enhanced the antitumor efficacy of paclitaxel because of increased drug penetration throughout the tumor. The optical imaging technology described here is thus a powerful, noninvasive, time-course imaging tool of functional tumor vessel normalization and its therapeutic consequences. Mol Cancer Ther; 10(7); 1173-84. Ó2011 AACR.

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“…5 The presence of VEGF in plateletderived growth factor (PDGF)-mediated angiogenesis inhibits pericyte coverage in immature vessels. 6 Bevacizumab, an antibody to the VEGF ligand, has been investigated as a targeted mechanism to normalize vessels in both preclinical and some clinical studies. 7 While these studies support the principle of vessel normalization to facilitate delivery of small molecules, 8,9 very few studies demonstrate improved delivery of larger, targeted cancer therapeutics such as monoclonal antibodies.…”

Section: Introductionmentioning

confidence: 99%