4.8 Article

Melatonin Alleviates Venous Dysfunction in a Mouse Model of Iliac Vein Occlusion

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.870981

Keywords

iliac vein occlusion; melatonin; venous permeability; venous inflammatory response; venous dysfunction

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This study established a mouse model of iliac vein occlusion (IVO) to investigate the effects of melatonin on injured veins. The results showed that melatonin reduced venous permeability, suppressed inflammation in the surrounding tissues, improved endothelial function, and inhibited vascular leakage.
The iliac vein can be severely stenosed and occluded due to thrombosis, tumor compression, or an anatomical abnormality. Such occlusion could result in limb swelling, venous claudication, and persistent leg ulcers. Its devastating sequelae heavily impact patients lifestyles and the social economy. Due to a lack of a stable and easy-to-operate iliac vein occlusion (IVO) model, its underlying molecular mechanism and pathophysiological process has not been completely understood. Melatonin (MLT) plays a critical role in anti-inflammation, but the potential protective effect of melatonin on venous dysfunction induced by IVO has not been revealed. In this study, a mouse model of IVO was established to study the effects of MLT on injured veins. The results of laser speckle images and Evans blue showed that MLT inhibited venous permeability in an IVO mouse model. Furthermore, MLT suppressed inflammation of surrounding tissues close to the affected vein by inhibiting the mRNA levels of TNF-alpha, IL-1 alpha, and MCP-1. In addition, endothelial injury was inhibited by MLT using zonula occludens protein-1 (ZO-1) staining. Taken together, we elucidated the therapeutic effect of MLT on vascular dysfunction induced by IVO, mainly by inhibiting the TNF-alpha, IL-1 alpha, and MCP-1 mRNA levels, improving endothelial function, and inhibiting vascular leakage.

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