Lianbiao Shan, Xin Wang, Yingrui Gu, Xiaodong Deng
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引用次数: 0
Abstract
Background: Atherosclerosis is the main pathological basis of cardiovascular events. Urinary 11-dehydrothromboxane B 2 (11-dhTXB2), as a stable metabolite of Thromboxane (TX) A2, may reflect platelet activity and plaque stability, but its mechanism is not clear.
Methods: A total of 160 patients with atherosclerosis were enrolled in this study. The correlation between urinary 11-dhTXB2 level and plaque morphology and inflammation index was detected. The effects of 11-dhTXB2 on macrophage polarization and endothelial barrier function were investigated by THP-1 macrophage and HUVEC co-culture model and ApoE-/- mouse model, and the intervention effects of curcumin and aspirin were evaluated.
Results: High levels of urinary 11-dhTXB2 were significantly associated with thinner fibrous cap and increased inflammatory markers, especially in diabetic patients with atherosclerosis and aspirin resistance. Cell experiments showed that activation of the TXA2 pathway (as indicated by elevated urinary 11-dhTXB2) promoted macrophage M1 polarization and impaired endothelial connexin expression. The combination of curcumin and aspirin can synergistically reduce urinary 11-dhTXB2, reduce plaque area and improve plaque stability. Notably, urinary 11-dhTXB2 serves as a stable metabolite reflecting in vivo TXA2 production and platelet activation, but is not itself a functional ligand acting on macrophages or endothelial cells.
Conclusion: Urinary 11-dhTXB2 can be used as a dynamic monitoring biomarker for the risk of atherosclerotic thrombosis. Elevated TXA2 pathway activity aggravates plaque instability by promoting inflammation and endothelial dysfunction. Curcumin combined with aspirin has the potential for synergistic intervention and provides a new strategy for individualized prevention and treatment.
期刊介绍：
Thrombosis Journal is an open-access journal that publishes original articles on aspects of clinical and basic research, new methodology, case reports and reviews in the areas of thrombosis.
Topics of particular interest include the diagnosis of arterial and venous thrombosis, new antithrombotic treatments, new developments in the understanding, diagnosis and treatments of atherosclerotic vessel disease, relations between haemostasis and vascular disease, hypertension, diabetes, immunology and obesity.
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