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Urokinase does not upregulate the vascular endothelial cell-mediated inflammatory response
J M Rhodes1, A F Tilberg, R R Gifford
1Department of Surgery, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center 17033, USA.
Journal of Vascular Surgery
|March 1, 1997
Summary
Urokinase, used for clot breakdown, does not harm vascular endothelial cells or increase inflammation at clinical doses. This suggests it won't trigger vascular inflammation in patients.
Area of Science:
- Vascular Biology
- Cellular Immunology
- Pharmacology
Background:
- Urokinase is a thrombolytic agent with established clinical use.
- Its direct impact on vascular endothelial cells remains largely uncharacterized.
- Understanding these effects is crucial for assessing potential inflammatory responses during treatment.
Purpose of the Study:
- To investigate the in vitro effects of urokinase on human umbilical vein endothelial cells (HUVEC).
- To assess urokinase's impact on HUVEC viability, growth, and adhesion molecule expression.
- To determine urokinase's influence on the interaction between HUVECs and leukocytes or platelets.
Main Methods:
- HUVECs were cultured with varying urokinase concentrations (0–10,000 IU/ml).
- Cell viability was assessed over 1–4 days.
- Adhesion of labeled leukocytes and platelets to HUVECs was quantified after 4–72 hours of urokinase exposure.
- Expression of key adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was measured via flow cytometry.
Main Results:
- Suprapharmacologic urokinase concentrations (>2000 IU/ml) reduced HUVEC viability.
- Clinically relevant urokinase concentrations (≤500 IU/ml) did not affect HUVEC viability or growth.
- No significant increase in leukocyte or platelet adhesion to HUVECs was observed.
- Urokinase did not upregulate the expression of tested adhesion molecules.
Conclusions:
- Urokinase at clinically relevant doses is safe for vascular endothelial cells in vitro.
- It does not induce cellular changes associated with the vascular inflammatory response.
- These findings imply that therapeutic use of urokinase is unlikely to initiate an in vivo vascular inflammatory response.