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Effect of PDIII inhibitor (Cilostazol) on ischemic angiogenesis in diabetic mice
Author(s) -
Otagiri Aoi,
Matsushita Shonosuke,
Sakakibara Yuzuru
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.625.4
Subject(s) - cilostazol , medicine , angiogenesis , enos , endocrinology , diabetes mellitus , progenitor cell , immunohistochemistry , artery , vascular endothelial growth factor , laser doppler velocimetry , blood flow , stem cell , vegf receptors , nitric oxide , biology , nitric oxide synthase , aspirin , genetics
Purpose Cilostazol (Cil) is a Class A drug for peripheral arterial disease (PAD) and used worldwide. Since diabetes mellitus (DM) is a main exacerbating factor of PAD, the effect of Cil on ischemic angiogenesis is investigated to clarify its beneficial effect on DM in regard to cellular and local components. Methods Male mice (n=18) were divided into three groups; Control (C), DM (D), and DM? (L). DM was induced by streptozocin. Cil was administered by oral intake. Femoral artery was ligated in all mice. 2 months after operation, mice were evaluated by (1) capillary density of soleus muscle, (2) Laser Doppler flow meter of posterior tibial artery, (3) number of endothelial progenitor cells (EPCs) by FCM, (4) analysis of immunohistochemistry (IHC) by eNOS antibody. Results Capillary density was decreased in DM compared to Control, however, DM? recovered to control level (C 15.1 7.6, D 9.6 4.1, L 14.1 3.5 per field; X400, p<0.05 C vs D, p<0.005 D vs L). Laser Doppler flow was as follows: (C 849%, D 6413%, L 63 6%, p<0.05 C vs D, p<0.001 C vs L). There was no difference in the number of EPCs among three groups (C 84, D 82, L 75 per µl). Mice with Cilostazol increased eNOS expression than DM by semiquantitative analysis (p<0.001). Conclusion Cilostazol enhanced angiogenesis in diabetic ischemic limb. It is not due to the involvement of bone‐marrow derived EPCs, but may due to enhanced eNOS expression.