Abstract 15719: Platelet Receptors GPIbα and GPIIb - Novel Mediators of Arteriogenesis?
The growth of preexistent collateral arteries into functional bypasses (arteriogenesis) is the only natural mechanism to compensate for the occlusion of a major artery. Whereas the recruitment of leukocytes (especially monocytes) into the perivascular space of growing collaterals has already been characterized as one of the critical steps, the role of platelets and their receptors have not been evaluated. In our study, thrombocytopenia (platelet reduction: 95%) was generated in C57BL/6 mice by treatment with anti-GPIbα depleting antibody (50 mcg/mouse). A different experimental group received a GPIbα inhibiting antibody in the same dosage. Controls were treated with 0.9% saline. On day 2 of treatment, arteriogenesis was induced via right femoral artery ligation (fal). GPIIb (aIIb integrin)-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) in all groups. Using intravital microscopy, the interaction of platelets with the endothelium of collateral arteries was quantified on day 3 after fal in GPIbα-/- 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 GPIbα inhibition only (0.51±0.06 vs. 0.79±0.04, p<0.005). The number of transiently adherent platelets at the endothelium of collateral arteries was significantly increased on the occluded side of control mice (21491±779 vs. sham 13931±1389, p<0.05) whereas in GPIbα-/- mice this effect was blunted (13435±2378 vs. sham 10095±3070). Perfusion recovery of GPIIb deficient mice improved significantly compared to 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 interact with the endothelium of growing collaterals via their GPIbα receptor thus promoting arteriogenesis by initiating important pathways like endothelial cell and leukocyte activation. GPIIb/IIIa inhibition improves perfusion recovery significantly and might therefore serve as a new therapeutic approach in patients.
- © 2011 by American Heart Association, Inc.