title: CD26 inhibition enhances perfusion recovery in ApoE-/-mice.
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.
  
  
  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.
authors: Laboratory of Experimental Cardiology, University Medical Center Utrecht, G02.523, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors: Rene T
authors: RT
authors: Haverslag
authors: Daphne
authors: D
authors: de Groot
authors: Sebastian
authors: S
authors: Grundmann
authors: Benjamin
authors: B
authors: Meder
authors: Marie-Jose
authors: MJ
authors: Goumans
authors: Gerard
authors: G
authors: Pasterkamp
authors: Imo E
authors: IE
authors: Hoefer
authors: Dominique P V
authors: DP
authors: de Kleijn
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005263:Femoral Artery / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008026:Ligation / Q000379:methods; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000378:metabolism; D010477:Perfusion / Q000379:methods; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D039481:CD11b Antigen; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D018819:Dipeptidyl Peptidase 4; C545245:Dpp4 protein, mouse