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
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