Short-term dexamethasone treatment inhibits vein graft thickening in hypercholesterolemic ApoE3Leiden transgenic mice Abbey Schepers, MD, Nuno M.M. Pires,

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Presentation transcript:

Short-term dexamethasone treatment inhibits vein graft thickening in hypercholesterolemic ApoE3Leiden transgenic mice Abbey Schepers, MD, Nuno M.M. Pires, MSc, Daniel Eefting, MD, Margreet R. de Vries, BSc, J. Hajo van Bockel, MD, PhD, Paul H.A. Quax, PhD Journal of Vascular Surgery Volume 43, Issue 4, Pages 809-815 (April 2006) DOI: 10.1016/j.jvs.2005.11.019 Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

Fig 1 Dexamethasone treatment (0.15 mg · kg−1 · d−1 in drinking water) reduces vein graft thickening in hypercholesterolemic ApoE3Leiden mice after 28 days of treatment. A, Quantification of vein graft thickening shows a reduction of 43% in the dexamethasone-treated animals as compared with controls (n = 6; ⁎P < .05), whereas no significant changes in luminal area were observed (B). C, Representative cross section; arrows indicate a thickened vessel wall (stain, hematoxylin-phloxin-saffron; original magnification, ×40). No differences were seen in the cellular composition of thickened grafts in either group, as determined by computer-assisted morphometric analysis. D, Alpha smooth muscle actin staining representing vascular smooth muscle cells. E, AIA31240 staining representing macrophages. n.s., Not significant; dexa, dexamethasone. Journal of Vascular Surgery 2006 43, 809-815DOI: (10.1016/j.jvs.2005.11.019) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

Fig 2 Effect of 7 days of dexamethasone treatment on vein graft thickening 28 days after surgery in hypercholesterolemic ApoE3Leiden mice. There was a significant inhibition of vein graft thickening in the 7-day-treated animals (A) when compared with controls (n = 6; ⁎P < .05). There was no significant difference in luminal area between groups (B). n.s., Not significant; dexa, dexamethasone. Journal of Vascular Surgery 2006 43, 809-815DOI: (10.1016/j.jvs.2005.11.019) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

Fig 3 Effect of dexamethasone treatment on the early messenger RNA (mRNA) expression of proinflammatory cytokines in injured vessels of ApoE3Leiden mice (n = 4 per group). The relative mRNA expression in time in the dexamethasone-treated group is depicted compared with mRNA expression the control group (expression in the control group was defined as 1; ⁎P < .05). MCP, Monocyte chemotactic protein; TNF, tumor necrosis factor; MIP, macrophage inflammatory protein; TLR, toll-like receptor. Journal of Vascular Surgery 2006 43, 809-815DOI: (10.1016/j.jvs.2005.11.019) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

Fig 4 Effect of either short-term (D7d) or prolonged (D28d) dexamethasone exposure (0.75 mg/mL of medium) in intimal hyperplasia formation in human saphenous vein organ cultures (n = 12 per group). In both dexamethasone-exposed groups, a significantly decreased amount of intimal hyperplasia was seen when compared with the control segments (⁎P < .05; original magnification, ×100; dotted line indicates the border separating media from intima). n.s., Not significant. Journal of Vascular Surgery 2006 43, 809-815DOI: (10.1016/j.jvs.2005.11.019) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions