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Jeffrey M. Rhodes, MD, Anna F. Tilberg, MS, Robert R.M. Gifford, MD 

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Presentation on theme: "Jeffrey M. Rhodes, MD, Anna F. Tilberg, MS, Robert R.M. Gifford, MD "— Presentation transcript:

1 Urokinase does not upregulate the vascular endothelial cell–mediated inflammatory response 
Jeffrey M. Rhodes, MD, Anna F. Tilberg, MS, Robert R.M. Gifford, MD  Journal of Vascular Surgery  Volume 25, Issue 3, Pages (March 1997) DOI: /S (97)70257-X Copyright © 1997 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

2 Fig. 1 Effects of urokinase on endothelial cell viability at 1 to 4 days. There was significantly decreased viability (▵ = p < 0.05 vs 0 IU/ml) at supratherapeutic urokinase concentrations of 2000 to 10,000 IU/ml by 4 days of treatment. n = 3 for each point. Journal of Vascular Surgery  , DOI: ( /S (97)70257-X) Copyright © 1997 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

3 Fig. 2 Effect of urokinase on endothelial cell growth. At therapeutic urokinase doses (≤500 IU/mL), there were no deleterious effects on HUVEC cell growth. Doubling times could not be calculated for 5000 or 10,000 IU/ml because of cytopathic effects at these concentrations. n = 3, p = NS. Journal of Vascular Surgery  , DOI: ( /S (97)70257-X) Copyright © 1997 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

4 Fig. 3 Relative adhesion of lymphocytes to HUVEC monolayers in face of urokinase (0 to 2000 IU/ml) or LPS (5 μg/ml) for 4, 24, 48, or 72 hours. Nontreated controls (0 IU/ml) were defined as 100%. Only LPS-stimulated HUVECs demonstrated significantly increased adhesion. § = p < 0.01 versus all other points at that time interval. ▵ = p < versus all other points. ANOVA at 72 hours: p = n = 3 to 5 for each time point. Journal of Vascular Surgery  , DOI: ( /S (97)70257-X) Copyright © 1997 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

5 Fig. 4 Relative adhesion of polymorphonuclear cells to HUVEC monolayers with urokinase (0 to 2000 IU/ml) or LPS (5 μg/ml) for 4, 24, 48, or 72 hours. Nontreated controls (0 IU/ml) were defined as 100%. Only LPS-stimulated HUVECs demonstrated statistically significant increased adhesion. ▵ = p < versus all other points, § = p < 0.01 versus all other points except 0 IU/ml (p < 0.05 vs 0 IU/ml). ANOVA at 72 hours: p = n = 3 to 5 for each time point. Journal of Vascular Surgery  , DOI: ( /S (97)70257-X) Copyright © 1997 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

6 Fig. 5 Relative adhesion of platelets to HUVEC monolayers in face of urokinase (0 to 2000 IU/ml) or LPS (5 μg/ml) for 4, 24, 48, or 72 hours. Nontreated controls (0 IU/ml) were defined as 100%. Only LPS-stimulated HUVECs at 4 hours demonstrated significantly increased adhesion. ▵ = p < 0.05 versus all other points at that time interval. n = 3 to 5 for each time point. Journal of Vascular Surgery  , DOI: ( /S (97)70257-X) Copyright © 1997 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

7 Fig. 6 Absolute percent of HUVECs with positive ICAM-1 labeling after 4, 24, or 48 hours of urokinase incubation. There was no significantly increased expression of ICAM-1 over that of urokinase nontreated control (0 IU/ml) compared with any urokinase concentration at any time tested. LPS stimulation at 5 μg/mL (used as positive control) was significantly elevated (p ≤ 0.01) at all time points compared with all urokinase concentrations tested. Percent positive cells at 4, 24, or 48 hours of LPS stimulation were 49.8%, 95.3%, and 93.9%, respectively (n = 6). Journal of Vascular Surgery  , DOI: ( /S (97)70257-X) Copyright © 1997 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

8 Fig. 7 Absolute percent of HUVECs with positive ELAM-1 labeling after 4, 24, or 48 hours of urokinase incubation. There was no significantly increased expression of ELAM-1 over that of nontreated urokinase control (0 IU/ml) compared with any urokinase concentration at any time tested. LPS stimulation at 5 μg/ml (used as positive control) was significantly elevated (p ≤ 0.05) at 4, 24, and 48 hours compared with all urokinase concentrations tested. Percent positive cells at 4, 24, or 48 hours of LPS stimulation were 61.5%, 14.6%, and 8.2%, respectively (n = 6, except 48 hours were n = 4). Journal of Vascular Surgery  , DOI: ( /S (97)70257-X) Copyright © 1997 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

9 Fig. 8 Absolute percent of HUVECs with positive VCAM-1 labeling after 4, 24, or 48 hours of urokinase incubation. There was no significantly increased expression of VCAM-1 over that of nontreated urokinase controls (0 IU/ml) compared with any urokinase concentration at any time tested. LPS stimulation at 5 μg/ml (used as positive control) was significantly elevated (p ≤ 0.01) at all time points compared with all urokinase concentrations tested. Percent positive cells at 4, 24, or 48 hours of LPS stimulation were 5.2%, 39.3%, and 27.9%, respectively (n = 6). Journal of Vascular Surgery  , DOI: ( /S (97)70257-X) Copyright © 1997 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

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