Levels and values of lipoprotein-associated phospholipase A2, galectin-3, RhoA/ROCK, and endothelial progenitor cells in critical limb ischemia: Pharmaco-therapeutic role of cilostazol and clopidogrel combination therapy

Jiunn-Jye Sheu, Pao Yuan Lin, Pei Hsun Sung, Yi Ching Chen, Steve Leu, Yung Lung Chen, Tzu Hsien Tsai, Han Tan Chai, Sarah Chua, Hsueh Wen Chang, Sheng Ying Chung, Chih Hung Chen, Sheung-fat Ko*, Hon Kan Yip

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

15 Scopus citations

Abstract

Objective: We tested the hypothesis that clopidogrel and cilostazol combination therapy could effectively attenuate systemic inflammatory reaction, facilitate proliferation of circulating endothelial progenitor cell (EPC), and improve the clinical outcomes of critical limb ischemia (CLI) in patients unsuitable for surgical revascularization or percutaneous transluminal angioplasty (PTA).Methods: A total 55 patients (mean age, 72 years; 56% female) were consecutively enrolled. Clopidogrel and cilostazol combination therapy was administered throughout the study period. Results: As compared with the baseline, circulating endothelial progenitor cell level (as shown by flow cytometry) was significantly increased (p < 0.003), whereas the CLI-related ulcers and painfulness were significantly improved (all p < 0.01) by day 90 after treatment. On the other hand, after clopidogrel and cilostazol combination therapy, galectin-3 level, lipoprotein-associated phospholipase A2 gene expression, and RhoA/ROCK-related protein expression in peripheral blood mononuclear cells were significantly suppressed (all p < 0.01). Eventually, by day 90, 5 patients (9.1%) died of other etiologies, 3 (5.5%) withdrew from the study, 6 (10.9%) required amputation, and the remaining 41 had satisfactory clinical improvement with complete wound healing in 9 (16.4%) patients. Conclusion: The results of the present study highlight that clopidogrel and cilostazol combination therapy may be considered to be an alternative method for treating patients with CLI unsuitable for surgical revascularization or PTA.

Original languageEnglish
Article number101
JournalJournal of Translational Medicine
Volume12
Issue number1
DOIs
StatePublished - 17 04 2014

Keywords

  • Cilostazol therapy
  • Clopidogrel
  • Critical limb ischemia
  • Endothelial progenitor cells
  • Inflammation

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