阿司匹林触发的DHA代谢物抑制了血管生成
M Vara-Messler1,2, L Trevisi1, E Zulato3
1Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Frontiers in pharmacology
|March 12, 2025
概括
多可萨赫萨酸 (DHA) 和阿司匹林 (ASA) 抑制了瘤中的新血管形成. 它们的综合作用,特别是通过DHA代谢物如17R-基-DHA,在实验室和动物模型中都显示出显著的抗血管性质.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 血管对于组织营养和免疫监测至关重要.
- 血管形成或血管生成的异常与癌症等疾病有关.
- 多可萨赫萨酸 (DHA) 和阿司匹林 (ASA) 已显示出潜在的抗癌作用,可能是通过向血管生成.
研究的目的:
- 研究DHA及其代谢物的抗血管性作用.
- 确定阿司匹林 (ASA) 在调节DHA抗血管性活性中的作用.
- 探索DHA对内皮细胞和新血管形成的影响背后的机制.
主要方法:
- 在体外测试 (MTT,伤口愈合,Boyden,Matrigel) 以评估内皮细胞的增殖,运动性和管形成.
- 在小鼠体内使用Matrigel海绵模型来测量血管生成.
- 液体染色学 - 双重质谱学 (LC-MS-MS) 用于识别脂质介质.
主要成果:
- DHA显著降低了内皮细胞迁移和管形成.
- 阿司匹林 (ASA) 增强了DHA的抗血管性作用,特别是通过代谢物17(R) - 基-DHA (17R-HDHA).
- 在体内,17R-HDHA及其代谢物17R-ResolvinD1降低了微血管密度.
结论:
- DHA表现出抗血管性质的特性,这些特性通过COX-2乙化被ASA强化.
- 代谢物17R-HDHA是DHA抗血管生成作用的关键调解物.
- 这些发现表明DHA和ASA在向瘤血管生成方面具有治疗潜力.
关键词:
17 (((R) - 基-多可萨赫萨酸 (17 (((R) -HDHA) 是一种17 (R) - 基-多可萨赫萨酸.血管新生的产生.阿司匹林 (ASA) 是一种多可萨赫萨酸 (DHA) 是一种多可萨赫萨酸.人类静脉内皮细胞 (HUVEC)更多相关视频
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
448
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
448
Mechanism of Angiogenesis
5.2K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.2K
Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
1.1K
Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
1.1K
Anticoagulant Drugs: Low-Molecular-Weight Heparins
588
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
588


