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AOP: 557
Title
β2-Receptor agonist leading to Cardiomyopathy
Short name
Graphical Representation
Point of Contact
Contributors
- Young Jun Kim
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
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This AOP was last modified on November 22, 2024 10:34
Revision dates for related pages
Page | Revision Date/Time |
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Increased activity, beta-2 adrenergic receptor | September 16, 2017 10:17 |
Abnormal Cardiac Structure and Function | July 31, 2023 00:59 |
Abstract
Stimulation of β2-adrenergic receptors, under pathological conditions, can contribute to the development of cardiomyopathy. While β2-receptors normally regulate myocardial contraction through Gs protein signaling, chronic or excessive activation leads to maladaptive changes in the myocardium. Sustained stimulation results in calcium overload, oxidative stress, and mitochondrial dysfunction, triggering apoptosis and promoting myocardial remodeling, including hypertrophy and fibrosis. Conditions such as stress cardiomyopathy (Takotsubo syndrome) and chronic sympathetic overactivation highlight the detrimental effects of β2-receptor overstimulation. Excessive catecholamine release or overuse of β2-selective agonists further exacerbates myocardial stress, progressing to structural and functional cardiac deterioration. Clinical manifestations include dilated cardiomyopathy, hypertrophic remodeling, and arrhythmias. Although β2-receptor activation is physiologically beneficial in acute settings, prolonged overstimulation can contribute to cardiomyopathy through mechanisms of calcium dysregulation and maladaptive remodeling.
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
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MIE | 1039 | Increased activity, beta-2 adrenergic receptor | Increased activity, beta-2 adrenergic receptor |
AO | 2157 | Abnormal Cardiac Structure and Function | Abnormal Cardiac Structure and Function |
Relationships Between Two Key Events (Including MIEs and AOs)
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Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Overall Assessment of the AOP
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Essentiality of the Key Events
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