Leukocyte (especially monocyte) recruitment is critical for collateral artery growth (arteriogenesis). The role of platelets and their receptors still remain to be evaluated. In our study, arteriogenesis was induced via right femoral artery ligation (fal) in 6 C57BL/6 mice under generated thrombocytopenia (platelet reduction: 95%) by treatment with anti-GPIba depleting antibody (50mg/mouse). A different experimental group received a GPIba inhibiting antibody in the same dosage. Controls were treated with 0.9% saline. 7 male GPIIb (_aIIbintegrin)-deficient mice and wildtype controls underwent fal to examine the function of the GPIIb/IIIa receptor. The outcome was monitored by Laser Doppler Imaging and quantified as relative perfusion recovery (right/left leg). Transiently adherent platelets at the endothelium of collateral arteries were quantified via intravital microscopy on day 3 in GPIba-/- and wildtype mice. Poor recovery on day 7 was observed under platelet depletion (0.49±0.04 vs. 0.79±0.04, p<0.005) as well as GPIba inhibition only (0.51±0.06 vs. 0.79±0.04, p<0.005). Platelet endothelial interaction was significantly increased on the occluded side of control mice (21491±779 vs. sham 13931±1389, p<0.05) whereas in GPIba-/- mice this effect was blunted (13435±2378 vs. sham 10095±3070). Perfusion recovery of GPIIb deficient mice was significantly better than controls on day 7 (0.75±0,19 vs. 0.53±0,14 p<0.05), day 14 (0.99±0.15 vs. 0.83±0,1 p<0.05) and day 21 (1.12±0.19 vs. 0.97±0,05 p<0.05).

Conclusion: 

Platelets promote arteriogenesis through interaction with the endothelium via their GPIba receptor and may initiate important pathways like endothelial cell and leukocyte activation. GPIIb/IIIa inhibition promotes arterial growth and might serve as a therapeutic target.