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Effect of Protein Kinase C inhibitor on angiogenesis in diabetic mice
Author(s) -
Kenmochi Reiko,
Matsushita Shonosuke,
Sugimori Haruhiko,
Sato Fujio,
Sakakibara Yuzuru
Publication year - 2008
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.22.1_supplement.746.13
Subject(s) - protein kinase c , angiogenesis , medicine , diabetes mellitus , endocrinology , microangiopathy , intraperitoneal injection , bisindolylmaleimide , neovascularization , streptozocin , diabetic retinopathy , streptozotocin , kinase , chemistry , biochemistry
Purpose: The outcome from therapeutic angiogenesis in diabetes mellitus (DM) is not satisfactory compared with non‐DM patients. In diabetes, protein kinase C (PKC) is activated according to intracellular high glucose concentration. And activated PKC is closely related to progression of diabetic microangiopathy. Recently, it was reported that blockade of PKC brought about beneficial effects on diabetic microangiopathy. From these backgrounds, we investigated effect of PKC inhibitor (bisindolylmaleimide: Bis) on angiogenesis in diabetic mice. Methods: Type I diabetes was induced by intraperitoneal administration of streptozocin (50mg/kg) for seven days in mice. After establishment of DM, Bis was injected ten days intraperitoneally (10 nM/day). Resection of femoral artery was conducted to develop hindlimb ischemia and erythropoietin (1,000 IU/kg, i.p.) was injected at the operation in all mice. Mice were divided into three groups (each n=6): Group A; DM(+) and Bis (−), Group B; DM(+) and Bis(+), Group C; DM(−) and Bis (−). Two weeks after the procedure, gastrocnemius muscles were resected. Vascular density and size of capillary vessels were compared by use of light microscopy in each group. Result: Vascular density of Groups A, B, C is as follows: 6.5+/−1.7, 11.0+/−3.5, 13.8+/−2.2 (per high power field), respectively (p<0.001; Group A vs. Group C, p<0.05; Group A vs. Group B). Conclusion: PKC inhibitor improved capillary density in Epo‐induced angiogenesis in diabetic mice. The use of PKC inhibitor may improve the clinical results of therapeutic angiogenesis in diabetic patients.