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可见光照射的改变会调节血小板功能并调控血栓形成。

Alterations in visible light exposure modulate platelet function and regulate thrombus formation.

作者信息

Andraska Elizabeth A, Denorme Frederik, Kaltenmeier Christof, Arivudainabi Aishwarrya, Mihalko Emily P, Dyer Mitchell, Annarapu Gowtham K, Zarisfi Mohammadreza, Loughran Patricia, Ozel Mehves, Williamson Kelly, Mota Alvidrez Roberto Ivan, Thomas Kimberly, Shiva Sruti, Shea Susan M, Steinman Richard A, Campbell Robert A, Rosengart Matthew R, Neal Matthew D

机构信息

Department of Surgery, Trauma and Transfusion Medicine Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA.

Department of Emergency Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

出版信息

J Thromb Haemost. 2025 Jan;23(1):123-138. doi: 10.1016/j.jtha.2024.08.020. Epub 2024 Sep 17.

Abstract

BACKGROUND

Variations in light exposure are associated with changes in inflammation and coagulation. The impact of light spectra on venous thrombosis (VT) and arterial thrombosis is largely unexplored.

OBJECTIVES

To investigate the impact of altering light spectrum on platelet function in thrombosis.

METHODS

Wild-type C57BL/6J mice were exposed to ambient (mice, 400 lux), blue (mice, 442 nm, 1400 lux), or red light (mice, 617 nm, 1400 lux) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, platelet aggregation, activation, transcriptomic, and metabolomic changes were measured. The ability of released products of platelet activation to induce thrombosis-generating neutrophil extracellular trap formation was quantified. Subsequent thrombosis was measured using murine models of VT and stroke. To translate our findings to human patients, light-filtering cataract patients were evaluated over an 8-year period for rate of venous thromboembolism with multivariable logistic regression clustered by hospital.

RESULTS

Exposure to long-wavelength red light resulted in reduced platelet aggregation and activation. RNA-seq analysis demonstrated no significant transcriptomic changes between mice and mice. However, there were global metabolomic changes in platelets from mice compared with mice. Releasate from activated platelets resulted in reduced neutrophil extracellular trap formation. Mice also had reduced VT weight and brain infarct size following stroke. On subgroup analysis of cataract patients, patients with a history of cancer had a lower lifetime risk of venous thromboembolism after implantation with lenses that filter low-wavelength light.

CONCLUSION

Light therapy may be a promising approach to thrombus prophylaxis by specifically targeting the intersection between innate immune function and coagulation.

摘要

背景

光照变化与炎症和凝血的改变有关。光谱对静脉血栓形成(VT)和动脉血栓形成的影响在很大程度上尚未得到探索。

目的

研究改变光谱对血栓形成中血小板功能的影响。

方法

将野生型C57BL/6J小鼠置于环境光(小鼠,400勒克斯)、蓝光(小鼠,442纳米,1400勒克斯)或红光(小鼠,617纳米,1400勒克斯)下,以12:12小时的光照:黑暗周期照射72小时。光照72小时后,测量血小板聚集、活化、转录组和代谢组的变化。对血小板活化释放产物诱导血栓形成的中性粒细胞胞外陷阱形成能力进行定量。随后使用VT和中风的小鼠模型测量血栓形成情况。为了将我们的研究结果转化到人类患者中,对滤光性白内障患者进行了为期8年的评估,通过医院聚类的多变量逻辑回归分析静脉血栓栓塞的发生率。

结果

暴露于长波长红光导致血小板聚集和活化减少。RNA测序分析表明小鼠之间无显著的转录组变化。然而,与小鼠相比,小鼠血小板存在整体代谢组变化。活化血小板的释放物导致中性粒细胞胞外陷阱形成减少。小鼠在中风后VT重量和脑梗死面积也减小。在白内障患者的亚组分析中,有癌症病史的患者在植入滤过低波长光的晶状体后,静脉血栓栓塞的终生风险较低。

结论

光疗可能是一种有前景的血栓预防方法,通过特异性靶向先天免疫功能和凝血之间的交叉点来实现。

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