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Event: 1443

Key Event Title

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


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
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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

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; 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
Atherosclerosis 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
Interaction with lung cells leading to atherosclerosis AdverseOutcome Ulla Vogel (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
All life stages 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

Atherosclerosis is defined as the thickening of the arterial wall towards the lumen. The thickening, called atherosclerotic plaques, is composed of macrophages, smooth muscle cells, lymphocytes, lipids (including cholesterol), and connective tissue. This thickening reduces the space in the blood vessels which is available for the blood flow (Widmaier, Raff, Strang, & Vander, 2016).

Atherosclerosis is initiated with an endothelial injury that allows the translocation of low density lipoprotein (LDL) molecules to the intima layer of the artery, where they become oxidized (oxLDL). The endothelial cells release chemokines and adhesion molecules that recruits blood monocytes to the injury site, where monocytes cross to the sub-endothelial space. Monocytes then differentiate into macrophages and take up oxLDL, thus becoming laden with lipoproteins (“foam cells”). The lipid accumulation and foam cell formation continues over time, and the migration of smooth muscle cells from the media layer to the intima space helps establishing an atherosclerotic plaque with the release extracellular matrix molecules (Libby et al., 2019).

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

Current in vitro models have been used to evaluate different parts of the atherosclerosis development, for example: expression of adhesion molecules, adhesion of monocytes to endothelial cells, monocytes migration and foam cell formation (Chen et al., 2021).

In animal models, the induction and/or progression of atherosclerosis after exposure to a stressor can be studied. Examples of these are the ApoE-/- and LdLr-/- mouse models and Watanabe rabbit model, where the development of atherosclerotic can be assessed (Gistera, Ketelhuth, Malin, & Hansson, 2022).

In humans, atheroscleorosis is diagnosed by clinicians. Techniques that allow direct visualization of atherosclerotic plaques include ultrasonography, computed tomography angiography, magnetic resonance imaging, and optical coherence tomography (Libby et al., 2019). These techniques can measure the intima thickness of arteries, along with detection of calcified components (Poyrazoglu, Vurdem, Arslan, & Uytun, 2016; van der Meer et al., 2004). Techniques that allow the evaluation of atherosclerosis without direct visualization of plaques include angiography, aortic pulse wave velocity and the ankle-arm systolic blood pressure index (Libby et al., 2019; Rodondi et al., 2010; van der Meer et al., 2004). Finally, nonspecific, inflammatory markers are also used to evaluate atherosclerosis. These include blood levels of interleukin 6 (IL-6), C-reactive protein and tumor necrosis factor α (TNF-α) (Rodondi et al., 2010).

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: Human.
  • Life stages applicability: All life stages. Although atherosclerosis is mostly observed in adult humans, this condition begins early in life, and progresses through adulthood (McGill, McMahan, & Gidding, 2008; McMahan et al., 2005). Children with chronic inflammation diseases have shown to develop atherosclerosis in early childhood. (Tyrrell et al., 2010; Yamamura et al., 2014)
  • Sex applicability: Unspecific, atherosclerosis is manifested in males and females (Libby, 2021).

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

Atherosclerosis is the principal cause of cardiovascular diseases including myocardial infarction, stroke and angina pectoris (Frostegard, 2013; Jebari-Benslaiman et al., 2022; Libby et al., 2019). In turn, cardiovascular diseases are the principal cause of deaths worldwide and measures have been made by many countries to control risk factors and prevent this disease (Vaduganathan, Mensah, Turco, Fuster, & Roth, 2022). It is pertinent to remark that ambient (outdoor) and indoor particulate matter are risk factors for cardiovascular and the World Health Organization (WHO) has estimated that 6.7 million annual premature deaths are associated with these risk factors (Vaduganathan et al., 2022; WHO, 2023).


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

Chen, J., Zhang, X., Millican, R., Lynd, T., Gangasani, M., Malhotra, S., . . . Jun, H. W. (2021). Recent Progress in in vitro Models for Atherosclerosis Studies. Front Cardiovasc Med, 8, 790529. doi:10.3389/fcvm.2021.790529

Frostegard, J. (2013). Immunity, atherosclerosis and cardiovascular disease. BMC Med, 11, 117. doi:10.1186/1741-7015-11-117

Gistera, A., Ketelhuth, D. F. J., Malin, S. G., & Hansson, G. K. (2022). Animal Models of Atherosclerosis-Supportive Notes and Tricks of the Trade. Circ Res, 130(12), 1869-1887. doi:10.1161/CIRCRESAHA.122.320263

Jebari-Benslaiman, S., Galicia-Garcia, U., Larrea-Sebal, A., Olaetxea, J. R., Alloza, I., Vandenbroeck, K., . . . Martin, C. (2022). Pathophysiology of Atherosclerosis. Int J Mol Sci, 23(6). doi:10.3390/ijms23063346

Libby, P. (2021). The changing landscape of atherosclerosis. Nature, 592(7855), 524-533. doi:10.1038/s41586-021-03392-8

Libby, P., Buring, J. E., Badimon, L., Hansson, G. K., Deanfield, J., Bittencourt, M. S., . . . Lewis, E. F. (2019). Atherosclerosis. Nat Rev Dis Primers, 5(1), 56. doi:10.1038/s41572-019-0106-z

McGill, H. C., Jr., McMahan, C. A., & Gidding, S. S. (2008). Preventing heart disease in the 21st century: implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Circulation, 117(9), 1216-1227. doi:10.1161/CIRCULATIONAHA.107.717033

McMahan, C. A., Gidding, S. S., Fayad, Z. A., Zieske, A. W., Malcom, G. T., Tracy, R. E., . . . McGill, H. C., Jr. (2005). Risk scores predict atherosclerotic lesions in young people. Arch Intern Med, 165(8), 883-890. doi:10.1001/archinte.165.8.883

Poyrazoglu, H. G., Vurdem, U. E., Arslan, A., & Uytun, S. (2016). Evaluation of carotid intima-media thickness in children with migraine: a marker of subclinical atherosclerosis. Neurol Sci, 37(10), 1663-1669. doi:10.1007/s10072-016-2648-0

Rodondi, N., Marques-Vidal, P., Butler, J., Sutton-Tyrrell, K., Cornuz, J., Satterfield, S., . . . Body Composition, S. (2010). Markers of atherosclerosis and inflammation for prediction of coronary heart disease in older adults. Am J Epidemiol, 171(5), 540-549. doi:10.1093/aje/kwp428

Tyrrell, P. N., Beyene, J., Feldman, B. M., McCrindle, B. W., Silverman, E. D., & Bradley, T. J. (2010). Rheumatic disease and carotid intima-media thickness: a systematic review and meta-analysis. Arterioscler Thromb Vasc Biol, 30(5), 1014-1026. doi:10.1161/ATVBAHA.109.198424

Vaduganathan, M., Mensah, G. A., Turco, J. V., Fuster, V., & Roth, G. A. (2022). The Global Burden of Cardiovascular Diseases and Risk: A Compass for Future Health. J Am Coll Cardiol, 80(25), 2361-2371. doi:10.1016/j.jacc.2022.11.005

van der Meer, I. M., Bots, M. L., Hofman, A., del Sol, A. I., van der Kuip, D. A., & Witteman, J. C. (2004). Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam Study. Circulation, 109(9), 1089-1094. doi:10.1161/01.CIR.0000120708.59903.1B

WHO. (2023). Ambient air pollution. Retrieved from

Widmaier, E. P., Raff, H., Strang, K. T., & Vander, A. J. (2016). Vander's human physiology : the mechanisms of body function (Fourteenth edition. ed.). New York, NY: McGraw-Hill.

Yamamura, K., Takada, H., Uike, K., Nakashima, Y., Hirata, Y., Nagata, H., . . . Hara, T. (2014). Early progression of atherosclerosis in children with chronic infantile neurological cutaneous and articular syndrome. Rheumatology (Oxford), 53(10), 1783-1787. doi:10.1093/rheumatology/keu180