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CEAP C2 级慢性静脉功能不全患者的局部和全身内皮损伤:硫酸软骨素的作用

Local and Systemic Endothelial Damage in Patients with CEAP C2 Chronic Venous Insufficiency: Role of Mesoglycan.

作者信息

Santoliquido Angelo, Carnuccio Claudia, Santoro Luca, Di Giorgio Angela, D'Alessandro Alessia, Ponziani Francesca Romana, Angelini Flavia, Izzo Marcello, Nesci Antonio

机构信息

Angiology and Noninvasive Vascular Diagnostics Unit, Department of Cardiovascular Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.

Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy.

出版信息

Int J Mol Sci. 2025 Apr 24;26(9):4046. doi: 10.3390/ijms26094046.

DOI:10.3390/ijms26094046
PMID:40362286
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12071570/
Abstract

Chronic venous disease (CVD) involves complex pathophysiological mechanisms, particularly an imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), contributing to venous remodeling and varicosities. Elevated MMP-2 and MMP-9 levels are commonly found in tissues affected by venous ulcers. Inflammation plays a central role in CVD, with higher levels of pro-inflammatory markers present in varicose veins compared to healthy ones. Syndecans, key components of the endothelial glycocalyx, are involved in inflammatory responses. Alterations in the glycocalyx structure are associated with vascular damage in both venous and arterial diseases. This study aimed to investigate inflammatory changes in CVD patients, focusing on glycocalyx damage and the therapeutic role of mesoglycan, a glycosaminoglycan-based drug. A prospective, monocentric study included 23 patients with C2 clinical-etiological-anatomical-pathological (CEAP) CVD. Serum samples were collected before and after mesoglycan treatment. Results showed significantly elevated levels of VCAM-1, MMP-2, MMP-9, SDC-1, IL-6, and IL-8 in blood from varicose veins versus the systemic circulation. Patients received 50 mg of mesoglycan orally every 12 h for 90 days. After treatment, a notable reduction in inflammatory markers was observed. These results support the hypothesis that mesoglycan may alleviate both local and systemic inflammation, providing insights into new therapeutic strategies for CVD management.

摘要

慢性静脉疾病(CVD)涉及复杂的病理生理机制,尤其是基质金属蛋白酶(MMPs)与其组织抑制剂(TIMPs)之间的失衡,这会导致静脉重塑和静脉曲张。在受静脉溃疡影响的组织中,通常会发现MMP-2和MMP-9水平升高。炎症在CVD中起核心作用,与健康静脉相比,静脉曲张中促炎标志物水平更高。Syndecans是内皮糖萼的关键组成部分,参与炎症反应。糖萼结构的改变与静脉和动脉疾病中的血管损伤有关。本研究旨在调查CVD患者的炎症变化,重点关注糖萼损伤以及基于糖胺聚糖的药物硫酸软骨素的治疗作用。一项前瞻性单中心研究纳入了23例C2临床-病因-解剖-病理(CEAP)CVD患者。在硫酸软骨素治疗前后采集血清样本。结果显示,与体循环相比,静脉曲张血液中VCAM-1、MMP-2、MMP-9、SDC-1、IL-6和IL-8水平显著升高。患者每12小时口服50毫克硫酸软骨素,持续90天。治疗后,炎症标志物显著降低。这些结果支持了硫酸软骨素可能减轻局部和全身炎症的假设,为CVD管理的新治疗策略提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff61/12071570/b239e93cf7a5/ijms-26-04046-g006.jpg
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本文引用的文献

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Syndecan-1: a key player in health and disease.Syndecan-1:健康与疾病中的关键角色。
Immunogenetics. 2024 Dec 17;77(1):9. doi: 10.1007/s00251-024-01366-4.
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SDC4 protein action and related key genes in nonhealing diabetic foot ulcers based on bioinformatics analysis and machine learning.基于生物信息学分析和机器学习的非愈合性糖尿病足溃疡中SDC4蛋白作用及相关关键基因
Int J Biol Macromol. 2024 Dec;283(Pt 2):137789. doi: 10.1016/j.ijbiomac.2024.137789. Epub 2024 Nov 17.
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Syndecans in Alzheimer's disease: pathogenetic mechanisms and potential therapeutic targets.阿尔茨海默病中的 Syndecans:发病机制及潜在治疗靶点
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Syndecan 4 is a marker of endothelial inflammation in pathological aging and predicts long-term cardiovascular outcomes in type 2 diabetes.Syndecan 4是病理性衰老中内皮炎症的标志物,并可预测2型糖尿病患者的长期心血管结局。
Diabetol Metab Syndr. 2024 Aug 20;16(1):203. doi: 10.1186/s13098-024-01431-8.
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Circulating glycocalyx shedding products as biomarkers for evaluating prognosis of patients with out-of-hospital cardiac arrest after return of spontaneous circulation.循环糖萼脱落产物作为评估院外心脏骤停患者自主循环恢复后预后的生物标志物。
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