title: Role of ischemia and of hypoxia-inducible genes in arteriogenesis after femoral artery occlusion in the rabbit.
abstract: Vascular endothelial growth factor (VEGF) is known to play an important role in angiogenesis. Its place in collateral artery growth (arteriogenesis), however, is still debated. In the present study, we analyzed the expression of VEGF and its receptors (Flk-1 and Flt-1) in a rabbit model of collateral artery growth after femoral artery occlusion. Hypoxia presents the most important stimulus for VEGF expression. We therefore also investigated the expression level of distinct hypoxia-inducible genes (HIF-1alpha, LDH A) and determined metabolic intermediates indicative for ischemia (ATP, creatine phosphate, and their catabolites). We found that arteriogenesis was not associated with an increased expression of VEGF or the mentioned hypoxia-inducible genes. Furthermore, the high-energy phosphates and their catabolites were entirely within normal limits. Despite the absence of an increased expression of VEGF and its receptors, collateral vessels increased their diameter by a factor of 10. The speed of collateral development could be increased by infusion of the chemoattractant monocyte chemotactic protein-1 but not by infusion of a 30 times higher concentration of VEGF. From these data, we conclude that under nonischemic conditions, arteriogenesis is neither associated with nor inducible by increased levels of VEGF and that VEGF is not a natural agent to induce arteriogenesis in vivo.
authors.affiliation: Max-Planck-Institute, Department of Experimental Cardiology, Bad Nauheim, Germany. e.deindl@kerckhoff.mpg.de
authors.forename: E
authors.initials: E
authors.lastname: Deindl
authors.forename: I
authors.initials: I
authors.lastname: Buschmann
authors.forename: I E
authors.initials: IE
authors.lastname: Hoefer
authors.forename: T
authors.initials: T
authors.lastname: Podzuweit
authors.forename: K
authors.initials: K
authors.lastname: Boengler
authors.forename: S
authors.initials: S
authors.lastname: Vogel
authors.forename: N
authors.initials: N
authors.lastname: van Royen
authors.forename: B
authors.initials: B
authors.lastname: Fernandez
authors.forename: W
authors.initials: W
authors.lastname: Schaper
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000503:physiopathology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology; D003097:Collateral Circulation; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D007511:Ischemia / Q000150:complications / Q000503:physiopathology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008026:Ligation; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D010725:Phosphocreatine / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors; D014654:Vascular Patency
chemical_list: D018932:Chemokine CCL2; D016228:Endothelial Growth Factors; D007527:Isoenzymes; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1