Abstract
Objective: The adaptive growth of blood vessels is important to prevent tissue loss following arterial occlusion. Extravasation of monocytes is essential for this process. The peptidase CD26 targets SDF-1 alpha, a chemokine regulating monocyte trafficking. We hypothesized that blocking SDF-1 alpha inactivation, using a commercially available CD26 inhibitor, accelerates perfusion recovery without detrimental side effects on plaque stability. Methods and Results: Atherosclerosis prone ApoE-/- mice underwent femoral artery ligation and received a CD26 inhibitor or placebo. CD26 inhibition increased short term (7 days) perfusion recovery after both single and daily doses compared to placebo, 36%±2 (p=0.017) and 39%±2 (p=0.008) vs. 29%±3 respectively. Long term (56 days) perfusion recovery increased after daily treatment compared to placebo 83%±3 vs. 60%±2, (p<0.001). CD26 inhibition did not result in increased atherosclerotic plaque instability or inflammatory cell infiltration. CD26 inhibition increased macrophage number around growing collaterals, SDF-1 alpha plasma levels and monocyte expression of the activation marker CD11b and the SDF-1 alpha receptor CXCR-4. Conclusions: CD26 inhibition enhanced perfusion recovery following arterial occlusion via attenuated SDF-1 alpha inactivation and increased monocyte activation. There was no observable aggravation of atherosclerosis and CD26 inhibition could therefore offer a novel approach for therapeutic arteriogenesis in patients.
Keywords: CD26, collateral circulation, leukocytes, perfusion recovery, SDF-1 alpha, monocyte activation
Current Vascular Pharmacology
Title:CD26 Inhibition Enhances Perfusion Recovery in ApoE-/-Mice
Volume: 11 Issue: 1
Author(s): Rene T. Haverslag, Daphne de Groot, Sebastian Grundmann, Benjamin Meder, Marie-Jose Goumans, Gerard Pasterkamp, Imo E. Hoefer and Dominique P.V. de Kleijn
Affiliation:
Keywords: CD26, collateral circulation, leukocytes, perfusion recovery, SDF-1 alpha, monocyte activation
Abstract: Objective: The adaptive growth of blood vessels is important to prevent tissue loss following arterial occlusion. Extravasation of monocytes is essential for this process. The peptidase CD26 targets SDF-1 alpha, a chemokine regulating monocyte trafficking. We hypothesized that blocking SDF-1 alpha inactivation, using a commercially available CD26 inhibitor, accelerates perfusion recovery without detrimental side effects on plaque stability. Methods and Results: Atherosclerosis prone ApoE-/- mice underwent femoral artery ligation and received a CD26 inhibitor or placebo. CD26 inhibition increased short term (7 days) perfusion recovery after both single and daily doses compared to placebo, 36%±2 (p=0.017) and 39%±2 (p=0.008) vs. 29%±3 respectively. Long term (56 days) perfusion recovery increased after daily treatment compared to placebo 83%±3 vs. 60%±2, (p<0.001). CD26 inhibition did not result in increased atherosclerotic plaque instability or inflammatory cell infiltration. CD26 inhibition increased macrophage number around growing collaterals, SDF-1 alpha plasma levels and monocyte expression of the activation marker CD11b and the SDF-1 alpha receptor CXCR-4. Conclusions: CD26 inhibition enhanced perfusion recovery following arterial occlusion via attenuated SDF-1 alpha inactivation and increased monocyte activation. There was no observable aggravation of atherosclerosis and CD26 inhibition could therefore offer a novel approach for therapeutic arteriogenesis in patients.
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T. Haverslag Rene, de Groot Daphne, Grundmann Sebastian, Meder Benjamin, Goumans Marie-Jose, Pasterkamp Gerard, E. Hoefer Imo and P.V. de Kleijn Dominique, CD26 Inhibition Enhances Perfusion Recovery in ApoE-/-Mice, Current Vascular Pharmacology 2013; 11 (1) . https://dx.doi.org/10.2174/1570161111309010021
DOI https://dx.doi.org/10.2174/1570161111309010021 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
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