Plasmin-PAI-1 Imbalance Contributes to Hyperglycemia-Induced Vascular Calcification
Yosuke Kanno1, Moeko Okuno2, Osamu Matsuo3
1Department of Molecular Pathology, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, Kyoto, Japan, ykanno@dwc.doshisha.ac.jp.
Journal of Vascular Research
|March 14, 2026
Summary
In diabetes, high glucose promotes vascular calcification (VC) via plasminogen activator inhibitor-1 (PAI-1). However, plasmin offers protection by activating AMPK and eNOS, suggesting therapeutic potential for VC in diabetes.
Area of Science:
- Cardiovascular Research
- Endocrinology
- Biochemistry
Background:
- Vascular calcification (VC) is a common diabetes complication, increasing thrombotic cardiovascular event risk.
- Diabetes impairs fibrinolysis, and fibrin deposition is implicated in VC, but the exact mechanisms are unclear.
Purpose of the Study:
- To investigate the role of fibrinolytic factors in high-glucose-induced VC.
- To explore the effects of plasmin on VC and related signaling pathways.
Main Methods:
- Utilized an in vitro model with vascular smooth muscle cells (VSMCs) under high-glucose conditions.
- Evaluated glucose-induced VC and plasminogen activator inhibitor-1 (PAI-1) expression.
- Assessed the impact of exogenous plasmin stimulation on VC and anti-calcific signaling.
Main Results:
- High glucose exacerbated VC and significantly increased PAI-1 expression.
- PAI-1 inhibition reduced glucose-induced VC, confirming its role in hyperglycemia.
- Exogenous plasmin decreased VC and activated protective AMPK-eNOS signaling.
Conclusions:
- PAI-1 contributes to hyperglycemia-associated VC, while plasmin demonstrates protective effects.
- Targeting PAI-1 or modulating plasmin activity may offer therapeutic strategies for diabetic VC.
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