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Published on: May 23, 2025
Age-Related Platelet Cox-1 Upregulation in Atrial Fibrillation
Emanuele Valeriani1, Vittoria Cammisotto2, Danilo Menichelli3
1Department of Internal Medicine, Endocrine and Metabolic Sciences, and Infectious Diseases, Azienda Ospedaliero-Universitaria Policlinico Umberto I, 00161 Rome, Italy.
Aging increases platelet activation by raising Cox-1 (cyclooxygenase-1) and thromboxane B2 (TxB2) levels. This age-related increase in Cox-1 partially explains higher TxB2 production and reduces aspirin
Area of Science:
- Cardiovascular Science
- Aging Research
- Pharmacology
Background:
- Aging is linked to heightened platelet activation, a potential driver of cardiovascular events.
- The precise mechanisms connecting aging to increased platelet activity remain incompletely understood.
- Platelet activation involves enzymes like cyclooxygenase-1 (Cox-1) and the production of thromboxane (Tx) B2.
Purpose of the Study:
- To investigate the relationship between aging, platelet Cox-1 expression, and thromboxane B2 production in patients with atrial fibrillation.
- To determine if Cox-1 mediates the association between age and TxB2 levels.
- To evaluate the impact of aging on aspirin's efficacy in inhibiting platelet activity in vitro.
Main Methods:
- Serum Cox-1 and TxB2 levels were measured in 134 atrial fibrillation patients.
- Correlation analyses assessed relationships between age, Cox-1, and TxB2.
- Mediation analysis examined Cox-1's role in the age-TxB2 association.
- In vitro experiments assessed aspirin's effect on platelet TxB2 production and Cox-1 expression across age groups.
Main Results:
- Serum Cox-1 and TxB2 levels showed a progressive increase with age.
- Significant positive correlations were observed between age and Cox-1, age and TxB2, and Cox-1 and TxB2.
- Cox-1 partially mediated the effect of age on TxB2 production.
- Aspirin demonstrated reduced inhibitory efficacy on platelet TxB2 production in older individuals (≥65 years) compared to younger ones.
- Older patients exhibited higher platelet Cox-1 expression, which correlated inversely with aspirin's inhibitory effect.
Conclusions:
- Aging is associated with increased platelet Cox-1 expression and thromboxane B2 production.
- Platelet Cox-1 plays a mediating role in the age-related increase in TxB2.
- Older individuals show impaired platelet inhibition by aspirin, linked to elevated Cox-1 levels.
- These findings highlight age-related changes in platelet function and aspirin response, relevant to cardiovascular risk in aging populations.
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