title: Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.
abstract: Studies in global androgen receptor knockout (G-ARKO) and orchidectomised mice suggest that androgen accelerates reperfusion of the ischaemic hindlimb by stimulating angiogenesis. This investigation used novel, vascular cell-specific ARKO mice to address the hypothesis that the impaired hindlimb reperfusion in G-ARKO mice was due to loss of AR from cells in the vascular wall.
  
  
  
  Mice with selective deletion of AR (ARKO) from vascular smooth muscle cells (SM-ARKO), endothelial cells (VE-ARKO), or both (SM/VE-ARKO) were compared with wild type (WT) controls. Hindlimb ischaemia was induced in these mice by ligation and removal of the femoral artery. Post-operative reperfusion was reduced in SM-ARKO and SM/VE-ARKO mice. Immunohistochemistry indicated that this was accompanied by a reduced density of smooth muscle actin-positive vessels but no change in the density of isolectin B4-positive vessels in the gastrocnemius muscle. Deletion of AR from the endothelium (VE-ARKO) did not alter post-operative reperfusion or vessel density. In an ex vivo (aortic ring culture) model of angiogenesis, AR was not detected in vascular outgrowths and angiogenesis was not altered by vascular ARKO or by exposure to dihydrotestosterone (DHT 10(-10)-10(-7)M; 6 days).
  
  
  
  These results suggest that loss of AR from vascular smooth muscle, but not from the endothelium, contributes to impaired reperfusion in the ischaemic hindlimb of G-ARKO. Impaired reperfusion was associated with reduced collateral formation rather than reduced angiogenesis.
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.|University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.
authors.forename: Junxi
authors.identifier: 0000-0002-1334-887X
authors.initials: J
authors.lastname: Wu
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.
authors.forename: Patrick W F
authors.initials: PW
authors.lastname: Hadoke
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.
authors.forename: Kaloyan
authors.initials: K
authors.lastname: Takov
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Korczak
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Denvir
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.
authors.forename: Lee B
authors.initials: LB
authors.lastname: Smith
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D000728:Androgens; D011944:Receptors, Androgen