Plasmin-PAI-1 Imbalance Contributes to Hyperglycemia-Induced Vascular Calcification.

IF 2.3 4区医学 Q3 PERIPHERAL VASCULAR DISEASE

Journal of Vascular Research Pub Date : 2026-03-14 DOI:10.1159/000551570

Yosuke Kanno, Moeko Okuno, Osamu Matsuo, Kei-Ichi Ozaki

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引用次数: 0

Abstract

Background: Vascular calcification (VC) is a frequent complication in diabetes and is linked to an increased risk of thrombotic cardiovascular events. Diabetes is characterized by impaired fibrinolysis, and accumulating evidence implicates fibrin deposition in VC progression. However, how fibrinolytic dysregulation contributes to VC remains unclear.

Methods: We examined the role of fibrinolytic factors in VC using an established in vitro model. Vascular smooth muscle cells (VSMCs) were cultured under high-glucose conditions to evaluate glucose-induced VC and plasminogen activator inhibitor-1 (PAI-1) expression. In addition, exogenous plasmin stimulation was performed to assess its effects on VC progression and anti-calcific signaling.

Results: High glucose enhanced VC and markedly increased PAI-1 expression. Inhibition of PAI-1 signaling attenuated glucose-induced VC, indicating its involvement in VC development under hyperglycemia. Conversely, exogenous plasmin reduced VC under normoglycemic conditions. Short-term plasmin stimulation activated AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS), both known inhibitors of VC.

Conclusion: These findings suggest that PAI-1 contributes to hyperglycemia-related VC, whereas plasmin exerts protective effects partly through AMPK-eNOS activation. Modulating plasmin activity or targeting PAI-1 may represent potential therapeutic approaches to prevent VC progression in diabetes.

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纤溶蛋白pai -1失衡有助于高血糖诱导的血管钙化。

背景：血管钙化（VC）是糖尿病的常见并发症，与血栓性心血管事件的风险增加有关。糖尿病的特点是纤维蛋白溶解受损，越来越多的证据表明纤维蛋白沉积在VC进展中。然而，纤溶异常如何导致VC仍不清楚。方法：建立体外模型，检测纤溶因子在VC中的作用。在高糖条件下培养血管平滑肌细胞（VSMCs），评估葡萄糖诱导的VC和纤溶酶原激活物抑制剂-1 （PAI-1）的表达。此外，采用外源性纤溶酶刺激来评估其对VC进展和抗钙化信号的影响。结果：高糖使VC增强，PAI-1表达明显升高。抑制PAI-1信号可减弱葡萄糖诱导的VC，表明其参与高血糖状态下VC的形成。相反，在正常血糖条件下，外源性纤溶酶降低VC。短期纤溶酶刺激可激活amp活化蛋白激酶（AMPK）和内皮型一氧化氮合酶（eNOS），两者都是已知的VC抑制剂。结论：PAI-1参与高血糖相关VC，而纤溶蛋白部分通过AMPK-eNOS激活发挥保护作用。调节纤溶酶活性或靶向PAI-1可能是预防糖尿病VC进展的潜在治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Vascular Research 医学-生理学

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The ''Journal of Vascular Research'' publishes original articles and reviews of scientific excellence in vascular and microvascular biology, physiology and pathophysiology. The scope of the journal covers a broad spectrum of vascular and lymphatic research, including vascular structure, vascular function, haemodynamics, mechanics, cell signalling, intercellular communication, growth and differentiation. JVR''s ''Vascular Update'' series regularly presents state-of-the-art reviews on hot topics in vascular biology. Manuscript processing times are, consistent with stringent review, kept as short as possible due to electronic submission. All articles are published online first, ensuring rapid publication. The ''Journal of Vascular Research'' is the official journal of the European Society for Microcirculation. A biennial prize is awarded to the authors of the best paper published in the journal over the previous two years, thus encouraging young scientists working in the exciting field of vascular biology to publish their findings.