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Event: 2384

Key Event Title

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

Decrease, Vascular integrity

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
Decrease, Vascular integrity
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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
Organ term
blood vessel

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
regulation of vascular permeability 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
PPARα activation leading to ELS mortality via reduced ATP KeyEvent You Song (send email) Under development: Not open for comment. Do not cite
PPARα activation leading to ELS mortality via ROS KeyEvent You Song (send email) Under development: Not open for comment. Do not cite

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
Danio rerio Danio rerio High NCBI
Oryzias latipes Oryzias latipes Moderate NCBI
Homo sapiens Homo sapiens Moderate NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Embryo High
Juvenile Moderate

Sex Applicability

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

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

A decrease in vascular integrity refers to the breakdown or functional loss of endothelial barrier properties within the vasculature. Under normal conditions, endothelial cells form a continuous, semi-permeable barrier that regulates the exchange of solutes, plasma, and cells between blood and tissue compartments. This KE is characterized by disruption of tight and adherens junctions, cytoskeletal contraction, or endothelial cell death, resulting in increased vascular permeability, leakage of plasma constituents, and, in severe cases, hemorrhage or edema.

In fish embryos, this manifests as pericardial edema, yolk sac swelling, or intracranial hemorrhage, often preceding hemopericardium (Event 2383). Mechanistically, decreased vascular integrity arises from ATP depletion, oxidative stress, or direct mitochondrial dysfunction in endothelial cells, consistent with perturbations observed after PPARα activation.

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

In vivo (fish embryos):

  • Fluorescent tracer leakage assay (microangiography): Injection of high-molecular-weight FITC- or TexasRed-dextran into circulation followed by time-lapse imaging to quantify extravasation.

    • Quantitative metric: Extravasation index (EI = F_extravascular / F_intravascular), leakage rate constant (kₗₑₐₖ), or % fluorescence outside vessels.

  • Evans Blue / sulforhodamine B uptake: Quantitative dye extraction or imaging to measure plasma leakage.

  • Pericardial or tissue edema scoring: Morphometric assessment of pericardial area or edema volume using image analysis.

  • Hemorrhage frequency or severity index: % embryos showing localized bleeding, particularly near the heart or brain.

In vitro (endothelial models):

  • Trans-Endothelial Electrical Resistance (TEER): Measures ionic conductance across endothelial monolayers; expressed as % decrease from baseline (Ω·cm²).

  • Macromolecular permeability (Papp): Apparent permeability coefficient using fluorescent dextrans in Transwell systems.

  • Immunostaining of junctional markers: Quantification of VE-cadherin or ZO-1 continuity index (proportion of intact junction length).

Domain of Applicability

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

The KE applies broadly to vertebrates with closed circulatory systems, particularly during vascular development. Evidence is strongest for teleost fish embryos, where vascular permeability and integrity can be directly visualized in vivo. Mechanistic conservation of endothelial junctional signaling (VE-cadherin, claudin-5, occludin) supports extrapolation to mammals, including humans. Most sensitive life stages: embryonic and early larval. Applicable to both sexes.

References

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