title: Arteriogenesis is modulated by bradykinin receptor signaling.
abstract: BACKGROUND
  Positive outward remodeling of pre-existing collateral arteries into functional conductance arteries, arteriogenesis, is a major endogenous rescue mechanism to prevent cardiovascular ischemia. Collateral arterial growth is accompanied by expression of kinin precursor. However, the role of kinin signaling via the kinin receptors (B1R and B2R) in arteriogenesis is unclear.
  
  
  OBJECTIVE
  The purpose of this study was to elucidate the functional role and mechanism of bradykinin receptor signaling in arteriogenesis.
  
  
  RESULTS
  Bradykinin receptors positively affected arteriogenesis, with the contribution of B1R being more pronounced than B2R. In mice, arteriogenesis upon femoral artery occlusion was significantly reduced in B1R mutant mice as evidenced by reduced microspheres and laser Doppler flow perfusion measurements. Transplantation of wild-type bone marrow cells into irradiated B1R mutant mice restored arteriogenesis, whereas bone marrow chimeric mice generated by reconstituting wild-type mice with B1R mutant bone marrow showed reduced arteriogenesis after femoral artery occlusion. In the rat brain 3-vessel occlusion arteriogenesis model, pharmacological blockade of B1R inhibited arteriogenesis and stimulation of B1R enhanced arteriogenesis. In the rat, femoral artery ligation combined with arterial venous shunt model resulted in flow-driven arteriogenesis, and treatment with B1R antagonist R715 decreased vascular remodeling and leukocyte invasion (monocytes) into the perivascular tissue. In monocyte migration assays, in vitro B1R agonists enhanced migration of monocytes.
  
  
  CONCLUSIONS
  Kinin receptors act as positive modulators of arteriogenesis in mice and rats. B1R can be blocked or therapeutically stimulated by B1R antagonists or agonists, respectively, involving a contribution of peripheral immune cells (monocytes) linking hemodynamic conditions with inflammatory pathways.
authors: Experimental and Clinical Research Center of the Charite and the Max Delbrueck Center for Molecular Medicine, Berlin, Germany. philipp.hillmeister@charite.de
authors: Philipp
authors: P
authors: Hillmeister
authors: Nora
authors: N
authors: Gatzke
authors: André
authors: A
authors: Dülsner
authors: Michael
authors: M
authors: Bader
authors: Ines
authors: I
authors: Schadock
authors: Imo
authors: I
authors: Hoefer
authors: Isabell
authors: I
authors: Hamann
authors: Carmen
authors: C
authors: Infante-Duarte
authors: Georg
authors: G
authors: Jung
authors: Kerstin
authors: K
authors: Troidl
authors: Daniel
authors: D
authors: Urban
authors: Philipp
authors: P
authors: Stawowy
authors: Marco
authors: M
authors: Frentsch
authors: Meijing
authors: M
authors: Li
authors: Stephanie
authors: S
authors: Nagorka
authors: Haitao
authors: H
authors: Wang
authors: Yu
authors: Y
authors: Shi
authors: Ferdinand
authors: F
authors: le Noble
authors: Ivo
authors: I
authors: Buschmann
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism / Q000503:physiopathology; D001158:Arteries / Q000254:growth & development* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000254:growth & development; D005263:Femoral Artery / Q000254:growth & development; D006614:Hindlimb / Q000098:blood supply; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000502:physiology*; D043782:Receptor, Bradykinin B2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2