title: Dysregulated selectin expression and monocyte recruitment during ischemia-related vascular remodeling in diabetes mellitus.
abstract: OBJECTIVE
  Diabetes mellitus (DM) is associated with impaired ischemia-related vascular remodeling and also dysregulation of the inflammatory response. We sought to determine whether impaired selectin-mediated monocyte recruitment in ischemic tissues contributes to blunted ischemia-mediated angiogenesis in DM.
  
  
  RESULTS
  Contrast-enhanced ultrasound perfusion imaging and molecular imaging of endothelial P-selectin expression in the proximal hindlimb were performed at 1, 3, and 21 days after arterial ligation in wild-type and db/db mice. Ligation reduced muscle blood flow to ≈0.05 mL/minute per gram in both strains. Significant recovery of flow occurred only in wild-type mice (60%-65% of baseline flow). On molecular imaging, baseline P-selectin signal was 4-fold higher in db/db compared with wild-type mice (P<0.01) but increased minimally at day 1 after ischemia, whereas signal increased approximately 10-fold in wild-type mice (P<0.01). Immunohistology of the hindlimb skeletal muscle demonstrated severely reduced monocyte recruitment in db/db mice compared with wild-type mice. Local treatment with monocyte chemotactic protein-1 corrected the deficits in postischemic P-selectin expression and monocyte recruitment in db/db mice and led to greater recovery in blood flow.
  
  
  CONCLUSIONS
  In DM, there is dysregulation of the selectin response to limb ischemia, which leads to impaired monocyte recruitment, which may be mechanistically related to reduced vascular remodeling in limb ischemia.
authors: Division of Cardiovascular Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
authors: Chad L
authors: CL
authors: Carr
authors: Yue
authors: Y
authors: Qi
authors: Brian
authors: B
authors: Davidson
authors: Scott
authors: S
authors: Chadderdon
authors: Ananda R
authors: AR
authors: Jayaweera
authors: J Todd
authors: JT
authors: Belcik
authors: Cameron
authors: C
authors: Benner
authors: Aris
authors: A
authors: Xie
authors: Jonathan R
authors: JR
authors: Lindner
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply* / Q000000981:diagnostic imaging; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000187:drug effects / Q000473:pathology*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019007:P-Selectin / Q000187:drug effects / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014463:Ultrasonography
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D019007:P-Selectin