title: Elevated fluid shear stress enhances postocclusive collateral artery growth and gene expression in the pig hind limb.
abstract: OBJECTIVE
  The role of fluid shear stress (FSS) in collateral vessel growth remains disputed and prospective in vivo experiments to test its morphogenic power are rare. Therefore, we studied the influence of FSS on arteriogenesis in a new model with extremely high levels of collateral flow and FSS in pig and rabbit hind limbs.
  
  
  RESULTS
  A side-to-side anastomosis was created between the distal stump of one of the bilaterally occluded femoral arteries with the accompanying vein. This clamps the collateral reentry pressure at venous levels and increases collateral flow, which is directed to a large part into the venous system. This decreases circumferential wall stress and markedly increases FSS. One week after anastomosis, angiographic number and size of collaterals were significantly increased. Maximal collateral flow exceeded by 2.3-fold that obtained in the ligature-only hind limb. Capillary density increased in lower leg muscles. Immunohistochemistry revealed augmented proliferative activity of endothelial and smooth muscle cells. Intercellular adhesion molecule-1 and vascular cell adhesion molecule (VCAM)-1 were upregulated, and monocyte invasion was markedly increased. In 2-dimensional gels, actin-regulating cofilin1 and cofilin2, destrin, and transgelin2 showed the highest degree of differential regulation.
  
  
  CONCLUSIONS
  High levels of FSS cause a strong arteriogenic response, reinstate cellular proliferation, stimulate cytoskeletal rearrangement, and normalize maximal conductance. FSS is the initiating molding force in arteriogenesis. The role of fluid shear stress on the development of a collateral circulation was studied by abruptly increasing collateral blood flow by a distal femoral artery-to-vein anastomosis. This increased number and size of collateral vessels to a hitherto unknown degree. Fluid shear stress is the primary and strongest arteriogenic stimulus.
authors.affiliation: Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, D-61231 Germany.
authors.forename: Frederic
authors.initials: F
authors.lastname: Pipp
authors.forename: Stefanie
authors.initials: S
authors.lastname: Boehm
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Cai
authors.forename: Farzin
authors.initials: F
authors.lastname: Adili
authors.forename: Bela
authors.initials: B
authors.lastname: Ziegler
authors.forename: Gordana
authors.initials: G
authors.lastname: Karanovic
authors.forename: Ralf
authors.initials: R
authors.lastname: Ritter
authors.forename: Jörn
authors.initials: J
authors.lastname: Balzer
authors.forename: Christian
authors.initials: C
authors.lastname: Scheler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schaper
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitz-Rixen
mesh_terms: D051339:Actin Depolymerizing Factors; D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D002455:Cell Division; D002634:Chemotaxis, Leukocyte; D051340:Cofilin 2; D003097:Collateral Circulation; D003599:Cytoskeleton / Q000648:ultrastructure; D051345:Destrin; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005263:Femoral Artery / Q000601:surgery; D005268:Femoral Vein / Q000601:surgery; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018056:Hemorheology; D006614:Hindlimb / Q000098:blood supply*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007511:Ischemia / Q000235:genetics / Q000503:physiopathology*; D008026:Ligation; D018810:Magnetic Resonance Angiography; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000502:physiology; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D013314:Stress, Mechanical; D034421:Sus scrofa; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051339:Actin Depolymerizing Factors; D051340:Cofilin 2; D051345:Destrin; D008840:Microfilament Proteins; D009124:Muscle Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1