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Low-dose aspirin increases 15-epi-lipoxins A4 in pregnancies at high-risk for developing preeclampsia
Veronica M Gonzalez-Brown1, Marwan Ma'ayeh2, Douglas A Kniss2
1Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, San Antonio Uniformed Services Health Science Consortium, Brooke Army Medical Center, Ft Sam Houston, TX, United States.
Insights
Low-dose aspirin (LDA) increases anti-inflammatory molecule 15-epi-lipoxin A4 (15-epi-LXA4) in high-risk pregnancies for preeclampsia. Lower 15-epi-LXA4 levels were observed in those who developed preeclampsia.
Area of Science:
- Obstetrics and Gynecology
- Pharmacology
- Immunology
Background:
- Low-dose aspirin (LDA) may prevent preeclampsia (PE) by triggering the biosynthesis of endogenous anti-inflammatory molecules, specifically aspirin-triggered 15-epi-lipoxin A4 (15-epi-LXA4).
- Understanding the role of 15-epi-LXA4 in LDA's mechanism of action is crucial for PE prevention strategies in high-risk pregnancies.
Purpose of the Study:
- To investigate the impact of daily LDA administration on the levels of 15-epi-LXA4 in pregnancies identified as high-risk for developing PE.
- To explore the relationship between 15-epi-LXA4 levels and the occurrence of PE in women receiving LDA.
Main Methods:
- A secondary analysis was conducted on data from a multi-centered randomized controlled trial involving high-risk pregnancies receiving daily LDA (60 mg).
- Maternal blood samples were collected at three time points: before LDA initiation, during 24-28 weeks gestation, and 34-36 weeks gestation.
- Levels of 15-epi-LXA4 were quantified using enzyme-linked immunosorbent assay (ELISA).
Main Results:
- The study included 82 patients, with 63 on LDA and 29 on placebo, commencing treatment between 13-25 weeks gestation.
- LDA administration significantly increased 15-epi-LXA4 levels compared to placebo, persisting throughout the study period (p < 0.001).
- In the LDA group, pregnancies that developed PE showed lower 15-epi-LXA4 levels compared to those that did not develop PE (p = 0.129).
Conclusions:
- Daily LDA significantly elevates 15-epi-LXA4 levels in high-risk pregnancies, suggesting a potential mechanism for PE prevention.
- Lower 15-epi-LXA4 levels in LDA-treated pregnancies complicated by PE indicate a possible association between reduced anti-inflammatory molecule levels and PE development.
Background:
LDA triggers biosynthesis of endogenous anti-inflammatory molecules, aspirin-triggered 15-epi-lipoxin A4 (15-epi-LXA4), which may counteract inflammatory process of preeclampsia (PE), and play role in LDA's mechanism of action in PE prevention in high-risk patients.
Objective:
Investigate the effects of daily LDA on levels of 15-epi-LXA4 in pregnancies at high-risk for developing PE.
Materials And Methods:
Secondary analysis of multi-centered randomized controlled trial investigating effects of daily LDA (60 mg) in high-risk pregnancies. Maternal samples were drawn at three points: before LDA initiation (13-26 weeks' gestation), 24-28 weeks' gestation (at least two weeks after LDA) and 34-36 weeks' gestation. 15-epi-LXA4 levels were measured by ELISA.
Results:
Analysis included 82 patients: 63 receiving daily LDA and 29 receiving daily placebo starting between 13 and 25 weeks gestation. Prior to randomization, baseline 15-epi-LXA4 levels were similar between both groups (75.9 pg/mL [IQR; 63.8-114.0] vs 136.2 pg/mL [52.4-476.2]; p = 0.10). Patients receiving daily LDA were noted to have significantly increased levels of 15-epi-LXA4 after LDA administration (136.2 pg/mL [IQR; 52.4-476.2] vs 1758.2 pg/mL [905.4-6638.5]; p < 0.001). They also had higher 15-epi-LXA4 levels compared to those receiving placebo at 24-28 weeks' (50.3 [38.1-94.2] vs 1758.2 [905.4-6638.5]; p < 0.001 and 34-38 weeks' gestation (57.9 [41.9-76.7] vs 2310.3 pg/mL [656.9-10609.4]; p < 0.001). After LDA administration in the second trimester, patients who developed PE had decrease in 15-epi-LXA4 levels compared to those without PE (942 pg/mL [348.3-1810.3] vs 1758.2 pg/mL [905.4-6638.5]; p = 0.129).
Conclusion:
Daily LDA administration increases 15-epi-LXA4 levels in high-risk pregnancies for PE. In LDA group, pregnancies complicated by PE have lower levels of 15-epi-LXA4 compared to pregnancies without PE.
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