Acetylsalicylic acid inhibition of the lipoxygenase pathway: Implications for HIV prevention

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Prostaglandins & other lipid mediators Pub Date : 2024-07-29 DOI:10.1016/j.prostaglandins.2024.106878

Monika M. Kowatsch , Tanja Winter , Julius Oyugi , Joshua Kimani , Julie Lajoie , Harold M. Aukema , Keith R. Fowke

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Abstract

Background

1.5 million new HIV infections occurred in 2021, suggesting new prevention methods are needed. Inflammation increases the risk for HIV acquisition by attracting HIV target cells to the female genital tract (FGT). In a pilot study, acetylsalicylic acid (ASA/Aspirin) decreased the proportion of FGT HIV target cells by 35 %. However, the mechanism remains unknown.

Methods

Women from Nairobi, Kenya took low-dose ASA (81 mg) daily for 6-weeks. Free oxylipins in the plasma were quantified by high-performance liquid chromatography-tandem mass spectroscopy.

Results

Oxylipins from 9 fatty acid substrates were detected, with more than one analyte from 4 substrates reduced post-ASA. Summary analysis found ASA downregulated cyclooxygenase and lipoxygenase but not cytochrome P450 activity with a lower n-6/n-3 oxylipin profile, reflecting reduced inflammation post-ASA.

Conclusions

Inflammation is associated with increased lipoxygenase activity and HIV risk. Our data suggests ASA reduces inflammation through downregulation of oxylipins. Understanding how ASA reduces inflammation may lead to novel HIV prevention approaches.

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乙酰水杨酸抑制脂氧合酶途径：对预防艾滋病的影响。

背景：2021 年新增 150 万艾滋病病毒感染者，这表明需要新的预防方法。炎症会吸引 HIV 靶细胞进入女性生殖道（FGT），从而增加感染 HIV 的风险。乙酰水杨酸（ASA/Aspirin）可将 FGT HIV 靶细胞的比例降低 35%。然而，其机制仍然不明：方法：肯尼亚内罗毕的妇女每天服用低剂量 ASA（81 毫克），持续 6 周。采用高效液相色谱-串联质谱法对血浆中的游离氧脂进行定量分析：结果：检测到 9 种脂肪酸底物中的氧脂素，其中 4 种底物中的一种以上的分析物在服用 ASA 后减少。总结分析发现，ASA 下调了环氧化酶和脂氧合酶的活性，但没有降低细胞色素 P450 的活性，同时降低了 n-6/n-3 氧脂素的含量，这反映了 ASA 后炎症的减轻：炎症与脂氧合酶活性增加和艾滋病风险有关。我们的数据表明，ASA 可通过下调氧化脂蛋白来减少炎症。了解 ASA 如何减少炎症可能会带来新的艾滋病预防方法。

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来源期刊

Prostaglandins & other lipid mediators 生物-生化与分子生物学

CiteScore

5.80

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： Prostaglandins & Other Lipid Mediators is the original and foremost journal dealing with prostaglandins and related lipid mediator substances. It includes basic and clinical studies related to the pharmacology, physiology, pathology and biochemistry of lipid mediators. Prostaglandins & Other Lipid Mediators invites reports of original research, mini-reviews, reviews, and methods articles in the basic and clinical aspects of all areas of lipid mediator research: cell biology, developmental biology, genetics, molecular biology, chemistry, biochemistry, physiology, pharmacology, endocrinology, biology, the medical sciences, and epidemiology. Prostaglandins & Other Lipid Mediators also accepts proposals for special issue topics. The Editors will make every effort to advise authors of the decision on the submitted manuscript within 3-4 weeks of receipt.