Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California, USA.
Clin Transl Sci. 2022 Oct;15(10):2378-2391. doi: 10.1111/cts.13366. Epub 2022 Jul 25.
Postmenopausal women are at increased risk for a cardiovascular event due to platelet hyperactivity. There is evidence suggesting that ω-3 polyunsaturated fatty acids (PUFAs) and ω-6 PUFAs have cardioprotective effects in these women. However, a mechanistic understanding of how these fatty acids regulate platelet function is unknown. In this study, we supplemented postmenopausal women with fish oil (ω-3 fatty acids) or evening primrose oil (ω-6 fatty acids) and investigated the effects on their platelet activity. The effects of fatty acid supplementation on platelet aggregation, dense granule secretion, and activation of integrin αIIbβ3 at basal levels and in response to agonist were tested in postmenopausal women following a supplementation and washout period. Supplementation with fish oil or primrose oil attenuated the thrombin receptor PAR4-induced platelet aggregation. Supplementation with ω-3 or ω-6 fatty acids decreased platelet dense granule secretion and attenuated basal levels of integrin αIIbβ3 activation. Interestingly, after the washout period following supplementation with primrose oil, platelet aggregation was similarly attenuated. Additionally, for either treatment, the observed protective effects post-supplementation on platelet dense granule secretion and basal levels of integrin activation were sustained after the washout period, suggesting a long-term shift in platelet reactivity due to fatty acid supplementation. These findings begin to elucidate the underlying mechanistic effects of ω-3 and ω-6 fatty acids on platelet reactivity in postmenopausal women. Hence, this study supports the beneficial effects of fish oil or primrose oil supplementation as a therapeutic intervention to reduce the risk of thrombotic events in postmenopausal women. https://clinicaltrials.gov/ct2/show/NCT02629497.
绝经后妇女由于血小板活性增加而面临更高的心血管事件风险。有证据表明，ω-3 多不饱和脂肪酸 (PUFA) 和 ω-6 PUFAs 对这些女性具有心脏保护作用。然而，这些脂肪酸如何调节血小板功能的机制尚不清楚。在这项研究中，我们给绝经后妇女补充鱼油（ω-3 脂肪酸）或月见草油（ω-6 脂肪酸），并研究它们对血小板活性的影响。在补充和洗脱期后，我们测试了脂肪酸补充对血小板聚集、致密颗粒分泌以及整合素 αIIbβ3 在基础水平和激动剂反应下的激活的影响。鱼油或月见草油补充可减轻凝血酶受体 PAR4 诱导的血小板聚集。ω-3 或 ω-6 脂肪酸补充可减少血小板致密颗粒分泌并减弱整合素 αIIbβ3 的基础激活水平。有趣的是，在洗脱期后，补充月见草油后血小板聚集也被减轻。此外，对于任何一种治疗，在洗脱期后，观察到的补充后对血小板致密颗粒分泌和基础整合素激活的保护作用仍然存在，这表明由于脂肪酸补充，血小板反应性发生了长期转变。这些发现开始阐明 ω-3 和 ω-6 脂肪酸对绝经后妇女血小板反应性的潜在机制影响。因此，本研究支持鱼油或月见草油补充作为治疗干预措施的有益效果，以降低绝经后妇女发生血栓事件的风险。https://clinicaltrials.gov/ct2/show/NCT02629497。
