Endogenous angiogenesis inhibitors

Folkman, Judah

doi:10.1111/j.1600-0463.2004.apm11207-0809.x

Cited by 300 publications

(225 citation statements)

References 69 publications

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“…Individual plasminogen kringles and various subsets of kringle domains have angiostatin activity, and many are more potent angiogenesis inhibitors than the 38-kd fragment containing K 1-4 , which was originally identified as angiostatin (51)(52)(53). Thus, the K 1-3 , K 1-5 , and K 1-4.5 (kringles 1-4 plus 85% of kringle 5) fragments exhibit more antiangiogenic activity than K 1-4 (12,54,55).…”

Section: Discussionmentioning

confidence: 99%

Antiangiogenic plasma activity in patients with systemic sclerosis

Mulligan-Kehoe¹,

Drinane²,

Mollmark³

et al. 2007

Arthritis & Rheumatism

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Objective. Systemic sclerosis (SSc; scleroderma) is a systemic connective tissue disease with an extensive vascular component that includes aberrant microvasculature and impaired wound healing. The aim of this study was to investigate the presence of antiangiogenic factors in patients with SSc.Methods. Plasma samples were obtained from 30 patients with SSc and from 10 control patients without SSc. The samples were analyzed for the ability of plasma to affect endothelial cell migration and vascular structure formation and for the presence of antiangiogenic activity.Results. Exposure of normal human microvascular dermal endothelial cells to plasma from patients with SSc resulted in decreased cell migration (mean ؎ SEM 52 ؎ 5%) and tube formation (34 ؎ 6%) compared with that in plasma from control patients (P < 0.001 for both). SSc plasma contained 2.9-fold more plasminogen kringle 1-3 fragments (angiostatin) than that in control plasma. The addition of angiostatin to control plasma resulted in inhibition of endothelial cell migration and proliferation similar to that observed in SSc plasma. In vitro studies demonstrated that granzyme B and other proteases contained in T cell granule content cleave plasminogen and plasmin into angiostatin fragments.Conclusion. Plasminogen conformation in patients with SSc enables granzyme B and granule content protease to limit the proangiogenic effects of plasmin and increase the levels of antiangiogenic angiostatin. This increase in angiostatin production may account for some of the vascular defects observed in patients with SSc.

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Section: Discussionmentioning

confidence: 99%

Antiangiogenic plasma activity in patients with systemic sclerosis

Mulligan-Kehoe¹,

Drinane²,

Mollmark³

et al. 2007

Arthritis & Rheumatism

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“…Angiogenesis is regulated by the orchestrated expression of endogenous regulatory elements (Carmeliet, 2005;Folkman, 1996Folkman, , 2002Folkman, , 2004Nyberg et al, 2005), which include an array of growth factors that stimulate and control the proliferation and migration of endothelial cells. There is also a growing population of endogenous regulators that work competitively by inhibiting both of these processes, thus suppressing angiogenesis.…”

Section: Combinatorial Identification Of a Sequence-function Correlatmentioning

confidence: 99%

“…Angiogenesis, the growth of new microvessels from the pre-existing vasculature, is tightly controlled by various endogenous regulators (Carmeliet, 2005;Folkman, 2004;Nyberg, Xie, & Kalluri, 2005). These regulatory elements include pro-and anti-angiogenic proteins or peptide fragments.…”

Section: Introductionmentioning

confidence: 99%

Peptides derived from type I thrombospondin repeat-containing proteins of the CCN family inhibit proliferation and migration of endothelial cells

Karagiannis

Popel

2007

The International Journal of Biochemistry & Cell Biology

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SummaryAngiogenesis, or neovascularization, is tightly orchestrated by endogenous regulators that promote or inhibit the process. The fine-tuning of these pro-and anti-angiogenic elements (the angiogenic balance) helps establish the homeostasis in tissues, and any aberration leads to pathologic conditions. The type I thrombospondin repeats are a family of protein structural elements involved in the control of angiogenesis, and some proteins containing these repeats have been identified as negative regulators of angiogenesis. Here we identify a set of 11 novel, anti-angiogenic 18-to 20-amino acid peptides that are derived from proteins that belong to the CCN protein family and contain type I thrombospondin motifs. We have named these peptides spondinstatin-1, cyrostatin, connectostatin, nephroblastostatin, wispostatin-2, wispostatin-3, netrinstatin-5C, netrinstatin-5D, adamtsostatinlike-4, fibulostatin-6.1, and complestatin-C6 to reflect their origin. We have shown that these peptides inhibit proliferation and migration of human umbilical vein endothelial cells in vitro. By conducting a clustering analysis of the amino acid sequences using sequence similarity criteria and of the experimental results using a hierarchical clustering algorithm, we have demonstrated that there is an underlying correlation between the sequence and activity of the identified peptides. This combination of experimental and computational approaches introduces a novel systematic framework for studying peptide activity, identifying novel peptides with anti-angiogenic activity, and designing mimetic peptides with tailored properties.

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“…19 Among the earliest discovered were angiostatin and endostatin, proteolytic degradation products of plasminogen and collagen XVIII, respectively. In addition, the soluble extracellular forms of receptors able to bind angiogenic factors, or peptide angiogenic inhibitors, are key effector molecules that can be used to inhibit angiogenesis via gene therapy.…”

Section: Antiangiogenic Strategiesmentioning

confidence: 99%

Gene therapy targeting to tumor endothelium

2006

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Tumor-associated vasculature is a relatively accessible component of solid cancers that is essential for tumor survival and growth, providing a vulnerable target for cancer gene therapy administered by intravenous injection. Several features of tumor-associated vasculature are different from normal vasculature, including overexpression of receptors for angiogenic growth factors, markers of vasculogenesis, upregulation of coagulation cascades, aberrant expression of adhesion molecules and molecular consequences of hypoxia. Many of these differences provide candidate targets for tumor-selective 'transductional targeting' of genetically-or chemically modified vectors and upregulated gene expression can also enable 'transcriptional targeting', regulating tumor endothelia-selective expression of transgenes following nonspecific gene delivery. Tumor vasculature also represents an important site of therapeutic action by the secreted products of antiangiogenic gene therapies that are expressed in non-endothelial cells. In this review we assess the challenges faced and the vectors that may be suitable for gene delivery to exploit these targets. We also overview some of the strategies that have been developed to date and highlight the most promising areas of research.

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Endogenous angiogenesis inhibitors

Cited by 300 publications

References 69 publications

Antiangiogenic plasma activity in patients with systemic sclerosis

Antiangiogenic plasma activity in patients with systemic sclerosis

Peptides derived from type I thrombospondin repeat-containing proteins of the CCN family inhibit proliferation and migration of endothelial cells

Gene therapy targeting to tumor endothelium

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