| First Author | Carr CL | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 11 | Pages | 2526-33 |
| PubMed ID | 21885854 | Mgi Jnum | J:191457 |
| Mgi Id | MGI:5461781 | Doi | 10.1161/ATVBAHA.111.230177 |
| Citation | Carr CL, et al. (2011) Dysregulated selectin expression and monocyte recruitment during ischemia-related vascular remodeling in diabetes mellitus. Arterioscler Thromb Vasc Biol 31(11):2526-33 |
| abstractText | 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 approximately 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. |
