Sitagliptin therapy enhances the number of circulating angiogenic cells and angiogenesis-evaluations in vitro and in the rat critical limb ischemia model

Sarah Chua, Jiunn Jye Sheu, Yung Lung Chen, Li Teh Chang, Cheuk Kwan Sun, Steve Leu, Hsin Ching Sung, Tzu Hsien Tsai, Sheng Ying Chung, Kuo Ho Yeh, Chung Lung Cho, Ying Hsien Kao, Hon Kan Yip*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

23 Scopus citations

Abstract

Background aims: We tested the hypothesis that sitagliptin is capable of increasing blood flow in the rat critical limb ischemia (CLI) model by enhancement of angiogenesis. Methods: Adipose tissue from adult-male Fischer 344 rats (n= 6) were cultured in endothelial progenitor cell culture medium for 14 d with (25 μmol/L) or without sitagliptin. CLI was induced by ligation of the left femoral artery. Rats (n= 32) were equally separated into four groups: untreated controls (group 1), sitagliptin (4 mg/kg per day; group 2), CLI (group 3) and CLI with sitagliptin (group 4). Results: In vitro, 7 and 14 d after cell culture, endothelial progenitor cell biomarkers assessed by flow cytometry (Sca-1/CD31+, CXCR4+, c- kit+ and CD34+ cells) and Western blot (vascular endothelial growth factor, CXCR4 and stromal-derived factor [SDF]-1α) were remarkably higher in group 4 than in the other groups (all P< 0.01). In vivo, 2 and 14 d after the CLI procedure, circulating angiogenic cell (Sca-1/CD31+, Sca-1+ and CD31+) numbers were significantly higher in group 4 than in the other groups (all P< 0.001). Additionally, the messenger RNA and protein expression of angiogenic biomarkers (CXCR4, SDF-1α and vascular endothelial growth factor), immunofluorescent staining of angiogenic cells (CXCR4+, SDF-1α+, CD31+, von Willebrand factor+ cells) and immunohistochemical staining of small vessel numbers in the ischemic area were significantly higher in group 4 than in the other groups (all P< 0.01). Furthermore, laser Doppler showed that the ratio of ischemic/normal blood flow was remarkably higher group 4 than in group 3 by days 14 and 28 after the CLI procedure (all P< 0.01). Conclusions: Sitagliptin therapy enhances circulating angiogenic cell numbers, angiogenesis and blood flow in the CLI area.

Original languageEnglish
Pages (from-to)1148-1163
Number of pages16
JournalCytotherapy
Volume15
Issue number9
DOIs
StatePublished - 09 2013

Keywords

  • Angiogenesis
  • Endothelial progenitor cells
  • Laser Doppler blood flow
  • Sitagliptin

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