title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Sheu
authors.forename: Pao-Yuan
authors.initials: PY
authors.lastname: Lin
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Sung
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chen
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.forename: Han-Tan
authors.initials: HT
authors.lastname: Chai
authors.forename: Sarah
authors.initials: S
authors.lastname: Chua
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Sheng-Ying
authors.initials: SY
authors.lastname: Chung
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. sfatko@adm.cgmh.org.tw.
authors.forename: Sheung-Fat
authors.initials: SF
authors.lastname: Ko
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000368:Aged; D001483:Base Sequence; D000077407:Cilostazol; D000077144:Clopidogrel; D017931:DNA Primers; D004359:Drug Therapy, Combination; D066026:Endothelial Progenitor Cells / Q000166:cytology; D005121:Extremities / Q000098:blood supply; D005260:Female; D037502:Galectin 3 / Q000378:metabolism*; D006801:Humans; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D037502:Galectin 3; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077144:Clopidogrel; D054460:rho-Associated Kinases; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000077407:Cilostazol; D013988:Ticlopidine
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