Enhanced arteriogenesis in mice overexpressing erythropoietin.
After permanent occlusion of the femoral artery, the survival of ischemic limb tissue depends on collateral artery growth (arteriogenesis). In previous work, we have shown that shear stress triggers arteriogenesis. To test whether increased shear stress results in enhanced arteriogenesis, we compared arteriogenesis in transgenic mice overexpressing erythropoietin (EPO), which possessed increased blood viscosity through the higher hematocrit (thereby providing increased shear stress), with wild-type mice. The right femoral artery was occluded proximal to the origin of the arteria poplitea. Distal blood flow was assessed by laser Doppler imaging, and the growth and remodeling of collateral arteries was examined by light and electron microscopy and morphometry. After occlusion of the femoral artery, EPO mice demonstrated enhanced arteriogenesis: their collateral arteries developed a 1.7-fold diameter and a 2-fold wall thickness compared with wild-type. However, the blood flow recovery in EPO mice was markedly retarded. Structural remodeling and growth of collateral arteries was markedly enhanced in EPO mice, presumably as a result of increased blood viscosity and shear stress.
Department of Exp. Cardiology, Max Planck Institute, Benekestrasse 2, 61231 Bad Nauheim, Germany. w.schaper@kerckhoff.mpg.de
Dimitri
D
Scholz
Wolfgang
W
Schaper
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D001809:Blood Viscosity; D003097:Collateral Circulation; D004921:Erythropoietin / Q000096:biosynthesis* / Q000235:genetics; D005121:Extremities / Q000098:blood supply*; D005263:Femoral Artery / Q000503:physiopathology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D033081:Shear Strength
D004921:Erythropoietin