Basic and Therapeutic Aspects of Angiogenesis

doi:10.1016/J.CELL.2011.08.039

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Basic and Therapeutic Aspects of Angiogenesis

Journal Article•DOI•

Basic and Therapeutic Aspects of Angiogenesis

Michael Potente¹, Holger Gerhardt², Holger Gerhardt³, Peter Carmeliet²•Institutions (3)

Goethe University Frankfurt¹, Katholieke Universiteit Leuven², London Research Institute³

16 Sep 2011-Cell (Cell)-Vol. 146, Iss: 6, pp 873-887

TL;DR: The emerging principles of vascular growth provide exciting new perspectives, the translation of which might overcome the current limitations of pro- and antiangiogenic medicine.

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About: This article is published in Cell.The article was published on 2011-09-16 and is currently open access. It has received 2278 citations till now. The article focuses on the topics: Sprouting angiogenesis & Angiogenesis.

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Journal Article•DOI•

Wound repair and regeneration: Mechanisms, signaling, and translation

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Sabine A. Eming¹, Paul Martin², Paul Martin³, Marjana Tomic-Canic⁴•Institutions (4)

University of Cologne¹, Cardiff University², University of Bristol³, University of Miami⁴

03 Dec 2014-Science Translational Medicine

TL;DR: In this review, emerging concepts in tissue regeneration and repair are highlighted, and some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies are provided.

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Abstract: The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body’s natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies.

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1,947 citations

Journal Article•DOI•

VEGF in Signaling and Disease: Beyond Discovery and Development.

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Rajendra S. Apte¹, Daniel S. Chen, Napoleone Ferrara²•Institutions (2)

Washington University in St. Louis¹, University of California, San Diego²

07 Mar 2019-Cell

TL;DR: This review will highlight critical nodal points in VEGF biology, including recent developments in immunotherapy for cancer and multitarget approaches in neovascular eye disease.

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1,179 citations

Cites background from "Basic and Therapeutic Aspects of An..."

...VEGF gradients induce tip cells and promote the formation of filopodia (De Bock et al., 2013; Eilken and Adams, 2010; Gerhardt et al., 2003; Gerhardt, 2008; Hellström et al., 2007; Potente et al., 2011; Ruhrberg et al., 2002)....
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Journal Article•DOI•

Microenvironmental regulation of tumour angiogenesis

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Michele De Palma¹, Daniela Biziato¹, Tatiana V. Petrova²•Institutions (2)

École Polytechnique Fédérale de Lausanne¹, Ludwig Institute for Cancer Research²

14 Jul 2017-Nature Reviews Cancer

TL;DR: The extrinsic regulation of angiogenesis by the tumour microenvironment is discussed, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.

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Abstract: Tumours display considerable variation in the patterning and properties of angiogenic blood vessels, as well as in their responses to anti-angiogenic therapy. Angiogenic programming of neoplastic tissue is a multidimensional process regulated by cancer cells in concert with a variety of tumour-associated stromal cells and their bioactive products, which encompass cytokines and growth factors, the extracellular matrix and secreted microvesicles. In this Review, we discuss the extrinsic regulation of angiogenesis by the tumour microenvironment, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.

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1,145 citations

Journal Article•DOI•

Establishment and Dysfunction of the Blood-Brain Barrier

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Zhen Zhao¹, Amy R. Nelson¹, Christer Betsholtz², Berislav V. Zlokovic¹•Institutions (2)

University of Southern California¹, Uppsala University²

19 Nov 2015-Cell

TL;DR: The mechanisms regulating the formation and maintenance of the BBB and functions of BBB-associated cell types are examined and the growing evidence associating BBB breakdown with the pathogenesis of inherited monogenic neurological disorders and complex multifactorial diseases, including Alzheimer's disease is discussed.

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1,034 citations

Cites background from "Basic and Therapeutic Aspects of An..."

...of the Blood-Brain Barrier...
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...At embryonic day E10 in mice, the angioblasts of the perineural vascular plexus penetrate the neuroectoderm guided by neuroectoderm-secreted vascular endothelial growth factor (VEGF), which results in formation of the nascent ‘‘leaky’’ blood vessels (Potente et al., 2011)....
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Journal Article•DOI•

Role of PFKFB3-Driven Glycolysis in Vessel Sprouting

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Katrien De Bock¹, Maria Georgiadou¹, Sandra Schoors¹, Anna Kuchnio¹, Brian W. Wong¹, Anna Rita Cantelmo¹, Annelies Quaegebeur¹, Bart Ghesquière¹, Sandra Cauwenberghs¹, Guy Eelen¹, Li-Kun Phng¹, Inge Betz¹, Bieke Tembuyser¹, Katleen Brepoels¹, Jonathan Welti¹, Ilse Geudens¹, Inmaculada Segura¹, Bert Cruys¹, Franscesco Bifari¹, Ilaria Decimo¹, Raquel Blanco², Sabine Wyns¹, Jeroen Vangindertael¹, Susana Rocha¹, Russel T Collins², Sebastian Munck¹, Dirk Daelemans¹, Hiromi Imamura³, Roland Devlieger¹, Mark H. Rider⁴, Paul P. Van Veldhoven¹, Frans Schuit¹, Ramon Bartrons⁵, Johan Hofkens¹, Peter Fraisl, Sucheta Telang⁶, Ralph J. DeBerardinis⁷, Luc Schoonjans¹, Stefan Vinckier⁶, Jason Chesney⁸, Holger Gerhardt⁹, Holger Gerhardt¹, Mieke Dewerchin¹, Peter Carmeliet¹ - Show less +40 more•Institutions (9)

Katholieke Universiteit Leuven¹, Cancer Research UK², Kyoto University³, Université catholique de Louvain⁴, University of Barcelona⁵, University of Louisville⁶, University of Texas Southwestern Medical Center⁷, University of Texas at Dallas⁸, London Research Institute⁹

01 Aug 2013-Cell

TL;DR: It is shown that ECs relied on glycolysis rather than on oxidative phosphorylation for ATP production and that loss of the gly colytic activator PFKFB3 in ECs impaired vessel formation.

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1,033 citations

Cites background from "Basic and Therapeutic Aspects of An..."

...Several genetic factors coordinate tip, stalk, and phalanx cell phenotypes (Geudens and Gerhardt, 2011; Potente et al., 2011)....
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...For instance, Notch signaling potently controls vessel branching by stimulating the stalk cell phenotype (Potente et al., 2011)....
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...Tip cells at the forefront of the vascular branch extend long filopodia and navigate but rarely proliferate, whereas trailing stalk cells proliferate to elongate the branch (Geudens and Gerhardt, 2011; Potente et al., 2011)....
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References

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Journal Article•DOI•

Tumor Angiogenesis: Therapeutic Implications

[...]

Judah Folkman

18 Nov 1971-The New England Journal of Medicine

TL;DR: This new capillary growth is even more vigorous and continuous than a similar outgrowth of capillary sprouts observed in 2016 and is likely to be accompanied by neovascularization.

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Abstract: THE growth of solid neoplasms is always accompanied by neovascularization. This new capillary growth is even more vigorous and continuous than a similar outgrowth of capillary sprouts observed in f...

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9,874 citations

"Basic and Therapeutic Aspects of An..." refers background in this paper

...Therapeutic Expectations and Challenges The importance of angiogenesis sparked hopes that manipulating this process could offer therapeutic opportunities (Folkman, 1971)....
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...The importance of angiogenesis sparked hopes that manipulating this process could offer therapeutic opportunities (Folkman, 1971)....
[...]

Journal Article•DOI•

Immunity, Inflammation, and Cancer

[...]

Sergei I. Grivennikov¹, Florian R. Greten², Michael Karin¹•Institutions (2)

University of California, San Diego¹, Technische Universität München²

19 Mar 2010-Cell

TL;DR: The principal mechanisms that govern the effects of inflammation and immunity on tumor development are outlined and attractive new targets for cancer therapy and prevention are discussed.

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8,664 citations

"Basic and Therapeutic Aspects of An..." refers background in this paper

...Tumor-associated macrophages, especially those polarized to a proangiogenic M2-like phenotype, stimulate angiogenesis by releasing PlGF that also contributes to vessel disorganization (Grivennikov et al., 2010; Qian and Pollard, 2010; Rolny et al., 2011)....
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Journal Article•DOI•

Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy

[...]

Rakesh K. Jain¹•Institutions (1)

Harvard University¹

07 Jan 2005-Science

TL;DR: Emerging evidence supporting an alternative hypothesis is reviewed—that certain antiangiogenic agents can also transiently “normalize” the abnormal structure and function of tumor vasculature to make it more efficient for oxygen and drug delivery.

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Abstract: Solid tumors require blood vessels for growth, and many new cancer therapies are directed against the tumor vasculature. The widely held view is that these antiangiogenic therapies should destroy the tumor vasculature, thereby depriving the tumor of oxygen and nutrients. Here, I review emerging evidence supporting an alternative hypothesis-that certain antiangiogenic agents can also transiently "normalize" the abnormal structure and function of tumor vasculature to make it more efficient for oxygen and drug delivery. Drugs that induce vascular normalization can alleviate hypoxia and increase the efficacy of conventional therapies if both are carefully scheduled. A better understanding of the molecular and cellular underpinnings of vascular normalization may ultimately lead to more effective therapies not only for cancer but also for diseases with abnormal vasculature, as well as regenerative medicine, in which the goal is to create and maintain a functionally normal vasculature.

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4,952 citations

"Basic and Therapeutic Aspects of An..." refers background in this paper

...Tumor Vessels Are Abnormal Tumor vessels display abnormal structure and function (Goel et al., 2011; Jain, 2005) with seemingly chaotic organization (Figure 7A)....
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...The resulting irregular perfusion impairs oxygen, nutrient, and drug delivery (Goel et al., 2011; Jain, 2005)....
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...The resulting sensitization to cytotoxic or radiation therapies relying on conversion of oxygen to radicals in combination with improved chemotherapeutic delivery may explain partly why combination delivery of bevacizumab/cytotoxic agents is often superior (Jain, 2005)....
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Journal Article•DOI•

Molecular mechanisms and clinical applications of angiogenesis

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Peter Carmeliet¹, Rakesh K. Jain²•Institutions (2)

Katholieke Universiteit Leuven¹, Harvard University²

19 May 2011-Nature

TL;DR: Preclinical and clinical studies have shown new molecular targets and principles, which may provide avenues for improving the therapeutic benefit from anti-angiogenic strategies.

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Abstract: Blood vessels deliver oxygen and nutrients to every part of the body, but also nourish diseases such as cancer. Over the past decade, our understanding of the molecular mechanisms of angiogenesis (blood vessel growth) has increased at an explosive rate and has led to the approval of anti-angiogenic drugs for cancer and eye diseases. So far, hundreds of thousands of patients have benefited from blockers of the angiogenic protein vascular endothelial growth factor, but limited efficacy and resistance remain outstanding problems. Recent preclinical and clinical studies have shown new molecular targets and principles, which may provide avenues for improving the therapeutic benefit from anti-angiogenic strategies.

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4,441 citations

"Basic and Therapeutic Aspects of An..." refers background in this paper

...Recent studies provided tremendous insights into fundamental aspects of angiogenesis that have led to amechanistic model of vessel branching (Adams and Alitalo, 2007; Carmeliet and Jain, 2011; Eilken and Adams, 2010; Phng and Gerhardt, 2009)....
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...Recent studies provided tremendous insights into fundamental aspects of angiogenesis that have led to amechanistic model of vessel branching (Adams and Alitalo, 2007; Carmeliet and Jain, 2011; Eilken and Adams, 2010; Phng and Gerhardt, 2009)....
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Journal Article•DOI•

Angiogenesis in health and disease.

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Peter Carmeliet¹•Institutions (1)

Katholieke Universiteit Leuven¹

01 Jun 2003-Nature Medicine

TL;DR: Molecular insights into the formation of new blood vessels are being generated at a rapidly increasing pace, offering new therapeutic opportunities that are currently being evaluated.

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Abstract: Blood vessels constitute the first organ in the embryo and form the largest network in our body but, sadly, are also often deadly. When dysregulated, the formation of new blood vessels contributes to numerous malignant, ischemic, inflammatory, infectious and immune disorders. Molecular insights into these processes are being generated at a rapidly increasing pace, offering new therapeutic opportunities that are currently being evaluated.

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4,137 citations

"Basic and Therapeutic Aspects of An..." refers background in this paper

...Inadequate vessel maintenance or growth causes ischemia in diseases such as myocardial infarction, stroke, and neurodegenerative or obesity-associated disorders, whereas excessive vascular growth or abnormal remodeling promotes many ailments including cancer, inflammatory disorders, and eye disease (Carmeliet, 2003; Folkman, 2007)....
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...…causes ischemia in diseases such as myocardial infarction, stroke, and neurodegenerative or obesity-associated disorders, whereas excessive vascular growth or abnormal remodeling promotes many ailments including cancer, inflammatory disorders, and eye disease (Carmeliet, 2003; Folkman, 2007)....
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