Division of Cardiovascular Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2526-33. doi: 10.1161/ATVBAHA.111.230177.
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.
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.
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.
糖尿病（DM）与缺血相关的血管重塑受损以及炎症反应失调有关。我们试图确定缺血组织中选择素介导的单核细胞募集受损是否导致 DM 中缺血介导的血管生成减弱。
在动脉结扎后第 1、3 和 21 天，在野生型和 db/db 小鼠的近侧后肢进行对比增强超声灌注成像和内皮 P 选择素表达的分子成像。结扎使两种品系的肌肉血流减少至≈0.05 毫升/分钟/克。仅在野生型小鼠中观察到显著的血流恢复（基线血流的 60%-65%）。在分子成像上，db/db 小鼠的基础 P 选择素信号比野生型小鼠高 4 倍（P<0.01），但在缺血后第 1 天增加很少，而野生型小鼠的信号增加了约 10 倍（P<0.01）。后肢骨骼肌的免疫组织化学显示，db/db 小鼠的单核细胞募集明显减少与野生型小鼠相比。局部给予单核细胞趋化蛋白-1 纠正了 db/db 小鼠缺血后 P 选择素表达和单核细胞募集的缺陷，并导致血流恢复更大。
在 DM 中，肢体缺血对选择素反应失调，导致单核细胞募集受损，这可能与肢体缺血中血管重塑减少有关。
