Effect of Shunting of Collateral Flow into the Venous System on Arteriogenesis and Angiogenesis in Rabbit Hind Limb

The aim of this study was to characterize the vascular remodeling in the external iliac artery (EIA) and the lower leg muscles in a rabbit shunt model created between the distal stump of the occluded femoral artery and the accompanying vein. Histology and immunoconfocal microscopy were used in this study. We found that: 1) both endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (P-eNOS) proteins were significantly increased in the shunt-side EIA; 2) matrix metalloproteinase-2 (MMP-2) expression was 5.5 times in shunt side EIA over that in normal EIA; 3) intercellular adhension molecule-1 (ICAM-1) expression was strongly induced in endothelial cells (EC) and vascular adhension molecule-1 (VCAM-1) expression was significantly increased in both EC and the adventitia of the shunt-side EIA; 4) augmentation of cell proliferation and extracellular proteolysis by macrophage infiltration was observed in shunt-side EIA; 5) cell proliferation was active in shunt side EIA, but quiet in shunt side lower leg’s arterial vessels; 6) capillary density in shunt side lower leg muscles was 2 times over that in normal side. In conclusion, our data demonstrate the paradigm that the power of shear stress takes the reins in arteriogenesis, whereas ischemia in angiogenesis, but not in arteriogenesis.