This Event is licensed under the Creative Commons BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.

Event: 1376

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increase, angiogenesis

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Explore in a Third Party Tool

Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Tissue

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
Breast carcinoma	VEGF-A complex	increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
Gastric ulcer formation	KeyEvent	Lyle Burgoon (send email)	Open for adoption
AhR activation to metastatic breast cancer	KeyEvent	Louise Benoit (send email)	Under Development: Contributions and Comments Welcome	Under Development
From SDH inactivation to cancer	KeyEvent	Sylvie Bortoli (send email)	Under development: Not open for comment. Do not cite	Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
human	Homo sapiens	High	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
Adults	High

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Male	High
Female	High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Angiogenesis is the physiological process through which new blood vessels form from existing vessels. This complex and tightly regulated process involves the proliferation and migration of endothelial cells, the remodeling of the extracellular matrix, and the recruitment of pericytes and smooth muscle cells.

Key Steps in Angiogenesis:

Stimulus for Angiogenesis: Angiogenesis is triggered by specific signals, such as growth factors, released in response to tissue hypoxia, injury, or other physiological needs.
Activation of Endothelial Cells: Endothelial cells in existing blood vessels become activated in response to angiogenic signals, leading to changes in gene expression and cell behavior.
Proliferation and Migration: Activated endothelial cells proliferate and migrate toward the angiogenic stimulus, guided by chemotactic signals.
Tube Formation: Endothelial cells organize into tube-like structures, forming capillaries. This process involves the creation of lumens within the tubes.
Vessel Maturation: The newly formed vessels undergo maturation processes, including the recruitment of pericytes and smooth muscle cells. This maturation is crucial for the stability and functionality of the vasculature.
Integration with Circulatory System: The newly formed blood vessels integrate into the existing circulatory system, providing increased blood flow to the target tissues.

Angiogenesis is regulated by both pro and anti-angiogenic factors. The most common pro angiogenic factors are VEGF and FGF (Folkman).

Angiogenesis is a fundamental mechanism in development, tissue repair, and various pathological conditions, including cancer :

Development: During embryonic development, angiogenesis is critical for establishing the vascular network necessary for organ and tissue formation (Ribatti).
Tissue Repair and Regeneration: Angiogenesis plays a key role in tissue repair and regeneration after injury or damage. The formation of new blood vessels helps supply nutrients and oxygen to the healing tissue (Ribatti).
Menstrual Cycle and Pregnancy: In the female reproductive system, angiogenesis is a normal part of the menstrual cycle and is essential for the development of the placenta during pregnancy (Hoier).
Inflammatory Response: Angiogenesis is involved in the inflammatory response, facilitating the influx of immune cells to sites of infection or injury.
Cancer Growth and Metastasis : In cancer, angiogenesis is hijacked by tumors to support their growth and metastasis. Tumors release pro-angiogenic factors, promoting the formation of new blood vessels that supply nutrients and oxygen to the growing cancer cells (Nishida).
Ischemic Diseases: Angiogenesis is a therapeutic target in diseases involving inadequate blood supply, such as ischemic heart disease and peripheral artery disease (Ferrara)

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Several assays are commonly employed (Staton, Stryker, Irvin):

Endothelial Cell Proliferation Assays: Assays like BrdU (bromodeoxyuridine) incorporation, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, or EdU (5-ethynyl-2'-deoxyuridine) incorporation can be used
Endothelial Cell Migration Assays: Transwell migration assays, scratch/wound healing assays, or microfluidic devices to study directed migration.
Tube Formation Assay: Assess the ability of endothelial cells to form capillary-like structures (Stryker)
Chorioallantoic Membrane (CAM) Assay: In vivo assay utilizing the chick embryo CAM to observe angiogenesis (Staton).
Matrigel Plug Assay: In vivo assay involving the subcutaneous injection of Matrigel containing angiogenic inducers or cells (Tahergorabi).
Aortic Ring Assay
Corneal Neovascularization Assay
Angiogenesis Imaging: as confocal microscopy or intravital microscopy to visualize blood vessel formation.
Quantitative PCR (qPCR) for Angiogenic Markers
ELISA for Angiogenic Factors

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Human

Mice

References

List of the literature that was cited for this KE description. More help

Staton CA, Stribbling SM, Tazzyman S, Hughes R, Brown NJ, Lewis CE. Current methods for assaying angiogenesis in vitro and in vivo. Int J Exp Pathol. 2004 Oct;85(5):233-48. doi: 10.1111/j.0959-9673.2004.00396.x. PMID: 15379956; PMCID: PMC2517524.

Irvin MW, Zijlstra A, Wikswo JP, Pozzi A. Techniques and assays for the study of angiogenesis. Exp Biol Med (Maywood). 2014 Nov;239(11):1476-88. doi: 10.1177/1535370214529386. Epub 2014 May 28. PMID: 24872440; PMCID: PMC4216737.

Tahergorabi Z, Khazaei M. A review on angiogenesis and its assays. Iran J Basic Med Sci. 2012 Nov;15(6):1110-26. PMID: 23653839; PMCID: PMC3646220.

Stryker ZI, Rajabi M, Davis PJ, Mousa SA. Evaluation of Angiogenesis Assays. Biomedicines. 2019 May 16;7(2):37. doi: 10.3390/biomedicines7020037. PMID: 31100863; PMCID: PMC6631830.

Nishida N, Yano H, Nishida T, Kamura T, Kojiro M. Angiogenesis in cancer. Vasc Health Risk Manag. 2006;2(3):213-9. doi: 10.2147/vhrm.2006.2.3.213. PMID: 17326328; PMCID: PMC1993983.

Ribatti, C. (2016). The crucial role of angiogenesis in embryogenesis. Life Sciences, 157, 17-22

Ribatti, C. (2014). The role of angiogenesis in wound healing. Journal of Vascular Research, 51(1), 2-11.

Reynolds, L. P., & Grazul-Balsas, J. L. (2010). Angiogenesis in the corpus luteum. Endocrine Reviews, 31(2), 226-240. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820779/

Hoier, J. D., & Hellström, M. (2014). Regulation of skeletal muscle angiogenesis by exercise training. Journal of Physiology, 592(11), 2523-2533. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104895/

Ferrara, N. (2005). VEGF as a therapeutic target in cancer. Cancer Cell, 8(6), 399-407.

Folkman, J. (2002). Angiogenesis: an essential step in tumor progression. Seminars in Oncology, 29(6), 315-322. [https://pubmed