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I. Marie, Dr., J.L. Bény  Journal of Investigative Dermatology 

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Presentation on theme: "I. Marie, Dr., J.L. Bény  Journal of Investigative Dermatology "— Presentation transcript:

1 Endothelial Dysfunction in Murine Model of Systemic Sclerosis: Tight-skin Mice 1 
I. Marie, Dr., J.L. Bény  Journal of Investigative Dermatology  Volume 119, Issue 6, Pages (December 2002) DOI: /j x Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 Appearance of endothelial cells within intact murine thoracic aortic wall in vitro, after loading with Fluo-4 and Fura-red, observed with laser line confocal microscopy. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 TSK 1+mice. Distribution and maximal fluorescence ratio of endothelial cells, within intact aortic wall, responsive to infusion of endothelium-dependent vasodilators (i.e., acetylcholine 10–5M, ATP 3×10–5M, bradykinin 10–7M, substance P 10–8M) and Iloprost (10–6M) observed with laser line confocal microscopy. The ratiometric images were obtained by dividing Fluo-4/Fura-red emitted fluorescence; they are presented as pseudo-colored images according to an intensity scale, lowest and highest values being in blue and in red, respectively. (i.e., in dark and in light, respectively, in black and white figures). The left images show the endothelial cells before infusion of endothelium-dependent vasodilators and Iloprost. The graphics demonstrate the kinetics of fluorescence intensity ratio within activated endothelial cells, in response to endothelium-dependent vasodilators and Iloprost. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 Control mice. Distribution and maximal fluorescence ratio of endothelial cells, within intact aortic wall, responsive to infusion of endothelium-dependent vasodilators (i.e., acetylcholine 10–5M, ATP 3×10–5M, bradykinin 10–7M, substance P 10–8M) and Iloprost (10–6M) observed with laser line confocal microscopy. The left images show the endothelial cells before infusion of endothelium-dependent vasodilators and Iloprost. The graphics demonstrate the kinetics of fluorescence intensity ratio within activated endothelial cells, in response to endothelium-dependent vasodilators and Iloprost. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

5 Figure 4 Reactivity of endothelial cells within thoracic aorta wall in vitro, in response to endothelium-dependent vasodilators (i.e., acetylcholine, ATP, bradykinin, substance P) and Iloprost, was assessed by both laser line confocal microscopy and pharmacologic tests in TSK 1+and control mice. Values are mean±SEM. The results were regarded as significant when p<0.05 (p-values<0.05 and 0.01 are presented as * and, **respectively). (A) Proportions of activated endothelial cells, in response to infusion of endothelium-dependent vasodilators and Iloprost, are expressed as percentages of observed fields total surface. (B) Maximal fluorescence ratio of activated endothelial cells, in response to infusion of endothelium-dependent vasodilators and Iloprost, are expressed as percentages of the baseline values. (C) Endothelium-dependent vasodilator- and Iloprost-induced relaxation of thoracic aortic rings with intact endothelium, using isometric tension measurement. The relaxation values are expressed as percentages of contraction to U46619 (3×10–7M) Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

6 Figure 5 Concentration–relaxation curves to both acetylcholine (A) and ATP (B) in thoracic aortic rings with intact endothelium of TSK 1+(—○—) and control (—▪—) mice. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

7 Figure 6 Concentration–relaxation curves to acetylcholine without and with incubation with NO (L-NAME, 10–4M) inhibitor. (A) Concentration–relaxation curves to acetylcholine in TSK 1+ mice, without (—○—) and with (—•—) incubation with NO inhibitor. (B) Concentration–relaxation curves to acetylcholine in control mice, without (—□—) and with (—▪—) incubation with NO inhibitor. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

8 Figure 7 Concentration–relaxation curves to ATP without and with incubation with NO (L-NAME, 10–4M) inhibitor. (A) Concentration–relaxation curves to ATP in TSK 1+ mice, without (—○—) and with (—•—) incubation with NO inhibitor. (B) Concentration–relaxation curves to ATP in control mice, without (—□—) and with (—▪—) incubation with NO inhibitor. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions


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