Dysregulated selectin expression and monocyte recruitment during ischemia-related vascular remodeling in diabetes mellitus

Chad L. Carr, Yue Qi, Brian Davidson, Scott Chadderdon, Ananda R. Jayaweera, J. Todd Belcik, Cameron Benner, Aris Xie, Jonathan R. Lindner

    Research output: Contribution to journalArticle

    30 Scopus citations

    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. Methods and 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. Conclusion-: 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.

    Original languageEnglish (US)
    Pages (from-to)2526-2533
    Number of pages8
    JournalArteriosclerosis, thrombosis, and vascular biology
    Volume31
    Issue number11
    DOIs
    StatePublished - Nov 1 2011

    Keywords

    • angiogenesis
    • inflammation
    • molecular imaging

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

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