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纤维蛋白原的结构变化及其在子宫内膜异位症相关血栓形成中的潜在作用。

Fibrinogen Structural Changes and Their Potential Role in Endometriosis-Related Thrombosis.

作者信息

Fini Eleonora, Argento Flavia Rita, Borghi Serena, Giurranna Elvira, Nencini Francesca, Cirillo Michela, Fatini Cinzia, Taddei Niccolò, Coccia Maria Elisabetta, Fiorillo Claudia, Becatti Matteo

机构信息

Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Firenze, 50134 Firenze, Italy.

Centre for Assisted Reproductive Technology, Division of Obstetrics and Gynaecology, Careggi University Hospital, 50134 Florence, Italy.

出版信息

Antioxidants (Basel). 2024 Nov 27;13(12):1456. doi: 10.3390/antiox13121456.

Abstract

Endometriosis (EM), a chronic inflammatory condition predominantly affecting women of reproductive age, has been linked to an elevated risk of thrombosis, though its underlying molecular mechanisms remain incompletely understood. In this case-control study, involving 71 EM patients and 71 matched controls, we explored the structural and functional changes in fibrinogen and their potential role in thrombosis. Key oxidative stress markers, such as reactive oxygen species (ROS) levels in blood lymphocytes, monocytes, and granulocytes, along with plasma lipid peroxidation markers and total antioxidant capacity, were measured. Fibrinogen structure was examined using circular dichroism spectroscopy and intrinsic fluorescence, while functional properties were evaluated by analyzing thrombin-mediated polymerization and plasmin-induced lysis. Compared to controls, EM patients exhibited elevated ROS production and systemic oxidative stress, leading to notable fibrinogen oxidation and structural alterations. These changes were associated with impaired fibrin polymerization and enhanced resistance to plasmin-induced lysis, which are indicative of a pro-thrombotic state. These findings suggest that oxidative stress-driven fibrinogen modifications may contribute to the heightened thrombotic risk in women with EM, highlighting a potential therapeutic target to mitigate cardiovascular complications.

摘要

子宫内膜异位症(EM)是一种主要影响育龄女性的慢性炎症性疾病,尽管其潜在分子机制尚不完全清楚,但它与血栓形成风险升高有关。在这项病例对照研究中,我们纳入了71例EM患者和71例匹配的对照,探讨了纤维蛋白原的结构和功能变化及其在血栓形成中的潜在作用。我们测量了关键的氧化应激标志物,如血液淋巴细胞、单核细胞和粒细胞中的活性氧(ROS)水平,以及血浆脂质过氧化标志物和总抗氧化能力。使用圆二色光谱和内源荧光检测纤维蛋白原结构,通过分析凝血酶介导的聚合反应和纤溶酶诱导的溶解来评估其功能特性。与对照组相比,EM患者表现出ROS产生增加和全身氧化应激,导致明显的纤维蛋白原氧化和结构改变。这些变化与纤维蛋白聚合受损和对纤溶酶诱导溶解的抵抗力增强有关,这表明处于血栓前状态。这些发现表明,氧化应激驱动的纤维蛋白原修饰可能导致EM女性血栓形成风险增加,突出了一个减轻心血管并发症的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c713/11673276/3d4949938f02/antioxidants-13-01456-g001.jpg

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