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Event: 2069

Key Event Title

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

Occurrence, Vascular Remodeling

Short name

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Biological Context

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Level of Biological Organization
Organ

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
blood vessel remodeling	blood vessel	occurrence

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
Deposition of energy leads to vascular remodeling	AdverseOutcome	Vinita Chauhan (send email)	Open for citation & comment

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	Moderate	NCBI
rat	Rattus norvegicus	Moderate	NCBI
mouse	Mus musculus	Moderate	NCBI

Life Stages

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

Life stage	Evidence
Adult	Moderate
Not Otherwise Specified	Moderate

Sex Applicability

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

Term	Evidence
Male	Moderate
Female	Low
Unspecific	Moderate

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

The vascular wall is composed of endothelial, smooth muscle and fibroblast cell interactions (Gibbons & Dzau, 1994; Renna, Heras & Miatello, 2013). The vasculature is capable of detecting changes in its surroundings and maintaining homeostasis (Gibbons & Dzau, 1994; Renna, Heras & Miatello, 2013). The functionality of blood vessels is highly dependent on their structure, with changes in arterial morphology being associated with downstream impacts (Gibbons & Dzau, 1994). Vascular remodeling is a term for many histological changes, including increased vascular stiffness, wall shear stress, intima-media thickening (IMT), increased intima-media section area, and increased vessel diameter (Herity et al., 1999). As blood vessels stiffen, this impacts systolic and diastolic pressure and pulse which can be indicators of vascular remodeling. Cellular level changes characterized by processes of growth, death, migration and production or degradation of the extracellular matrix (ECM) result in inflammation (increase in VCAM, ICAM, cytokines, chemokines) and calcification (changes in ratios of collagen and elastin) (Gibbons & Dzau, 1994). Initial tissue injury and resulting remodeling can also lead to turbulent blood flow causing further structural changes like increased vessel fibrosis. Increased vascular remodelling is often associated with a build-up of plaque in the arteries (known as atherosclerosis) due to impaired healing, which forces the vessel walls to attempt to remodel to maintain blood flow (Sylvester et al., 2018).

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

Assay	Reference	Description	OECD Approved Assay
Pulse wave velocity (PWV)	(Soucy et al., 2007; Soucy et al., 2010; Soucy et al., 2011)	Used to measure blood vessel stiffness. Calculated using measurements from a Doppler probe and electrocardiogram (ECG).	No
NIS-Elements image analysis software (Nikon)	(Soucy et al., 2011)	Used to measure intraluminal perimeter (which in turn is used to calculate circular luminal diameter) and vessel wall thickness.	No
Hematoxylin-eosin (HE) staining	(Shen et al., 2018; Su et al., 2020; Delp et al., 2000, Cheng et al., 2017, Yu et al., 2011)	Used to measure aortic wall thickness, intima-media wall thickness (IMT), wall shear stress, outer media perimeter, and media cross section area (CSA).	No
Wire myography	(Tarasova et al., 2020)	Blood vessels are mounted in wire myograph systems and the relaxed inner diameter is estimated from the passive length-tension relationship between each artery.	No
Verhoeff-van Gieson staining	(Sofronova et al., 2015)	Measures elastin-collagen content in blood vessels, with Verhoeff stain highlighting elastin and van Gieson highlighting collagen. The higher the ratio of elastin to collagen, the greater the distensibility of the vessel. A higher collagen ratio is associated with increased vascular stiffness.	No
Sonography	(Lee et al., 2020; Sarkozy et al., 2019; Sridharan et al., 2020)	Uses ultrasound waves to measure IMT and intima-media area, both of which are markers of vascular structure and are used to calculate vascular stiffness.	No

Domain of Applicability

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

Taxonomic applicability: Vascular remodelling is applicable to all species with a closed circulatory system where blood is transported throughout the body via blood vessels with corresponding vessel walls (Renna, Heras & Miatello, 2013). Closed circulatory systems are present in most vertebrates and some invertebrates.

Life stage applicability: This key event is not life stage specific. However, advancing age is a risk factor for vascular remodeling (Harvey, Montezano & Touyz, 2015).

Sex applicability: This key event is not sex specific. However, men are shown to develop vascular remodeling younger than women (Kessler et al., 2019).

Evidence for perturbation by a stressor: Current literature provides ample evidence of vascular remodelling being induced by stressors including ionizing radiation exposure and altered gravity (Shen et al. 2018; Su et al., 2020; Delp et al., 2000, Cheng et al., 2017, Yu et al., 2011; Soucy et al., 2007; Soucy et al., 2010; Soucy et al., 2011).

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

References

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

Cheng, Y. P. et al. (2017), "Acid sphingomyelinase/ceramide regulates carotid intima-media thickness in simulated weightless rats", Pflugers Archiv European Journal of Physiology, Vol. 469, Springer Nature, London, https://doi.org/10.1007/s00424-017-1969-z

Delp, M.D. et al. (2000), “Structural and functional remodeling of skeletal muscle microvasculature is induced by simulated microgravity”, American Journal of Physiology - Heart and Circulatory Physiology, Vol. 278, American Physiological Society, Rockville, https://doi.org/10.1152/ajpheart.2000.278.6.h1866

Gibbons, G. H., and V. J. Dzau (1994), “The Emerging Concept of Vascular Remodeling”, New England Journal of Medicine, Vol. 330/20, Massachusetts Medical Society, Waltham, https://doi.org/10.1056/NEJM199405193302008

Harvey, A., A. C. Montezano, & R. M. Touyz. (2015), “Vascular biology of ageing-Implications in hypertension”, Journal of molecular and cellular cardiology, Vol. 83, Elsevier, Amsterdam, https://doi.org/10.1016/j.yjmcc.2015.04.011

Herity, N.A. et al. (1999), “Review: Clinical Aspects of Vascular Remodeling”, Journal of Cardiovascular Electrophysiology, Vol.10/7, Wiley, https://doi.org/10.1111/j.1540-8167.1999.tb01273.x

Kessler, E. L. et al. (2019), “Sex-specific influence on cardiac structural remodeling and therapy in cardiovascular disease”, Biology of Sex Differences, Vol. 10, Springer Nature, https://doi.org/10.1186/s13293-019-0223-0

Lee, S. M. C. et al. (2020), “Arterial structure and function during and after long-duration spaceflight”, Journal of Applied Physiology, Vol. 129, American Physiological Society, Rockville, https://doi.org/10.1152/japplphysiol.00550.2019

Patel, S. (2020), "The effects of microgravity and space radiation on cardiovascular health: From low-Earth orbit and beyond", IJC Heart and Vasculature, Vol. 30, Elsevier, Amsterdam, https://doi.org/10.1016/j.ijcha.2020.100595.

Renna, N. F., N. Heras, R. M. Miatello (2013), “Pathophysiology of Vascular Remodeling in Hypertension”, International Journal of Hypertension, Vol. 2013, Hindawi, London, http://doi.org/10.1155/2013/808353

Sárközy, M. et al. (2019), "Selective heart irradiation induces cardiac overexpression of the pro-hypertrophic miR-212", Frontiers in Oncology, Vol. 9, Frontiers Media S.A., Lausanne, https://doi.org/10.3389/FONC.2019.00598/FULL

Shen, Y. et al. (2018), “Transplantation of bone marrow mesenchymal stem cells prevents radiation-induced artery injury by suppressing oxidative stress and inflammation”, Oxidative Medicine and Cellular Longevity, Vol. 2018, Hindawi, London, https://doi.org/10.1155/2018/5942916.

Sofronova, S. I. et al. (2015), “Spaceflight on the Bion-M1 biosatellite alters cerebral artery vasomotor and mechanical properties in mice”, Journal of Applied Physiology, Vol. 118/7, American Physiological Society, Rockville, https://doi.org/10.1152/japplphysiol.00976.2014.

Soucy, K. G. et al. (2011), “HZE 56Fe-ion irradiation induces endothelial dysfunction in rat aorta: Role of xanthine oxidase”, Radiation Research, Vol. 176/4, Radiation Research Society, Bozeman, https://doi.org/10.1667/RR2598.1.

Soucy, K. G. et al. (2010), “Dietary inhibition of xanthine oxidase attenuates radiation-induced endothelial dysfunction in rat aorta”, Journal of Applied Physiology, Vol. 108/5, American Physiological Society, Rockville, https://doi.org/10.1152/japplphysiol.00946.2009.

Soucy, K. G. et al. (2007), “Single exposure gamma-irradiation amplifies xanthine oxidase activity and induces endothelial dysfunction in rat aorta”, Radiation and Environmental Biophysics, Vol. 46, Springer, New York, https://doi.org/10.1007/s00411-006-0090-z.

Sridharan, V. et al. (2020), "Effects of single-dose protons or oxygen ions on function and structure of the cardiovascular system in male Long Evans rats", Life Sciences in Space Research, Vol. 26, Elsevier, Amsterdam, https://doi.org/10.1016/j.lssr.2020.04.002.

Su, Y. T. et al. (2020), "Acid sphingomyelinase/ceramide mediates structural remodeling of cerebral artery and small mesenteric artery in simulated weightless rats", Life Sciences, Vol. 243, Elsevier, Amsterdam, https://doi.org/10.1016/j.lfs.2019.117253.

Sylvester, C. B. et al. (2018), "Radiation-Induced Cardiovascular Disease: Mechanisms and Importance of Linear Energy Transfer", Frontiers in Cardiovascular Medicine, Vol. 5, Frontiers Media SA, Lausanne, https://doi.org/10.3389/fcvm.2018.00005.

Tarasova, O. S. et al. (2020), "Simulated Microgravity Induces Regionally Distinct Neurovascular and Structural Remodeling of Skeletal Muscle and Cutaneous Arteries in the Rat", Frontiers in Physiology, Vol. 1, Frontiers Media SA, Lausanne, https://doi.org/10.3389/fphys.2020.00675.

Yu, T. et al. (2011), "Iron-ion radiation accelerates atherosclerosis in apolipoprotein E-Deficient mice", Radiation Research, Vol. 175/6, Radiation Research Society, Bozeman, https://doi.org/10.1667/RR2482.1.