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Urokinase plasminogen activator system in humans with stable coronary artery disease
T L Krasnikova1, Y Parfyonova, I A Alekseeva
1Cardiology Research Centre of Ministry of Health, Moscow, Russia.
Insights
Patients with stable coronary artery disease (SCAD) show elevated plasma urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) levels. This suggests a potential impairment in fibrinolytic ability, impacting blood clot breakdown in SCAD patients.
Area of Science:
- Cardiovascular Research
- Hemostasis and Thrombosis
- Molecular Biology
Background:
- Stable coronary artery disease (SCAD) involves complex interactions of coagulation and fibrinolysis.
- Urokinase plasminogen activator (uPA) and its inhibitor PAI-1 play critical roles in fibrinolysis.
- Understanding their levels in SCAD is crucial for assessing thrombotic risk.
Purpose of the Study:
- To compare plasma uPA peptide levels, PAI-1 activity, and urokinase receptors (uPAR) on monocytes in SCAD patients versus healthy controls.
- To investigate potential alterations in the fibrinolytic system associated with SCAD.
Main Methods:
- Plasma uPA levels measured by ELISA.
- PAI-1 activity determined using a plasmin generation assay.
- uPAR and CD11b/CD18 expression on monocytes analyzed via flow cytometry.
Main Results:
- SCAD patients exhibited significantly higher plasma uPA peptide levels compared to healthy subjects (P < 0.05).
- Plasma PAI-1 activity was also significantly elevated in SCAD patients versus controls (P < 0.05).
- No significant differences were observed in uPAR or CD11b/CD18 expression on monocytes between groups.
Conclusions:
- Patients with SCAD demonstrate increased plasma levels of uPA and PAI-1.
- The observed pattern suggests a potential impairment in fibrinolytic function in SCAD.
- Further research is warranted to explore the clinical implications of these findings in SCAD management.
Abstract:
1. The present study compares plasma urokinase plasminogen activator (uPA) peptide levels, plasma plasminogen inhibitor (PAI-1) activity and urokinase receptors (uPAR) on peripheral blood monocytes of patients with stable coronary artery disease (SCAD) and healthy volunteers. 2. Urokinase plasminogen activator levels were analysed by ELISA and PAI-1 activity was determined by a plasmin generation method using the chromogenic substrate S2390. Relative uPAR numbers and the adhesion molecules CD11b/CD18 on peripheral blood monocytes were estimated using specific antibodies and flow cytometry. 3. Patients with SCAD were found to have higher plasma uPA peptide levels than age-matched healthy subjects (10.40 +/- 0.99 vs 8.25 +/- 0.53 pmol/L, respectively; P < 0.05). 4. Plasma PAI-1 activity was also higher in patients with SCAD than in healthy subjects (13.6 +/- 2.5 vs 5.2 +/- 1.0 IU/mL, respectively; P < 0.05). 5. Relative uPAR and CD11b/CD18 adhesion molecules were similar on peripheral blood monocytes of patients with SCAD and in healthy subjects. 6. The data indicate a pattern of expression/activity of uPA and PAI-1 in patients with SCAD suggestive of an impaired fibrinolytic ability.