title: The range of adaptation by collateral vessels after femoral artery occlusion.
abstract: Natural adaptation to femoral artery occlusion in animals by collateral artery growth restores only approximately 35% of adenosine-recruitable maximal conductance (C(max)) probably because initially elevated fluid shear stress (FSS) quickly normalizes. We tested the hypothesis whether this deficit can be mended by artificially increasing FSS or whether anatomical restraints prevent complete restitution. We chronically increased FSS by draining the collateral flow directly into the venous system by a side-to-side anastomosis between the distal stump of the occluded femoral artery and the accompanying vein. After reclosure of the shunt collateral flow was measured at maximal vasodilatation. C(max) reached 100% already at day 7 and had, after 4 weeks, surpassed (2-fold) the C(max) of the normal vasculature before occlusion. Expression profiling showed upregulation of members of the Rho-pathway (RhoA, cofilin, focal adhesion kinase, vimentin) and the Rho-antagonist Fasudil markedly inhibited arteriogenesis. The activities of Ras and ERK-1,-2 were markedly increased in collateral vessels of the shunt experiment, and infusions of L-NAME and L-NNA strongly inhibited MAPK activity as well as shunt-induced arteriogenesis. Infusions of the peroxinitrite donor Sin-1 inhibited arteriogenesis. The radical scavengers urate, ebselen, SOD, and catalase had no effect. We conclude that increased FSS can overcome the anatomical restrictions of collateral arteries and is potentially able to completely restore maximal collateral conductance. Increased FSS activates the Ras-ERK-, the Rho-, and the NO- (but not the Akt-) pathway enabling collateral artery growth.
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Inka
authors.initials: I
authors.lastname: Eitenmüller
authors.forename: Oscar
authors.initials: O
authors.lastname: Volger
authors.forename: Alexander
authors.initials: A
authors.lastname: Kluge
authors.forename: Kerstin
authors.initials: K
authors.lastname: Troidl
authors.forename: Miroslav
authors.initials: M
authors.lastname: Barancik
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Cai
authors.forename: Matthias
authors.initials: M
authors.lastname: Heil
authors.forename: Frederic
authors.initials: F
authors.lastname: Pipp
authors.forename: Silvia
authors.initials: S
authors.lastname: Fischer
authors.forename: Anton J G
authors.initials: AJ
authors.lastname: Horrevoets
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitz-Rixen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schaper
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000503:physiopathology*; D001158:Arteries / Q000254:growth & development; D002478:Cells, Cultured; D003097:Collateral Circulation / Q000502:physiology*; D005263:Femoral Artery / Q000473:pathology*; D020869:Gene Expression Profiling; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000235:genetics*; D011817:Rabbits; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000235:genetics
chemical_list: D020928:Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins