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The peroxisome proliferator-activated receptor-gamma agonist pioglitazone increases number and function of endothelial progenitor cells in patients with coronary artery disease and normal glucose tolerance . OBJECTIVE Peroxisome proliferator-activated receptor-gamma ( PPAR gamma ) agonists ( thiazolidinediones [ TZDs ] ) are used for the treatment of diabetes . Bone marrow-derived endothelial progenitor cells ( EPCs ) improve vascular function and predict cardiovascular risk . The effect of pioglitazone therapy on EPCs was examined . RESEARCH DESIGN AND METHODS AND RESULTS We performed a prospective , randomized , double-blind study on patients with documented stable coronary artery disease and normal glucose tolerance . Of 54 patients with normal fasting glucose levels , 18 showed impaired glucose tolerance and 36 patients with normal glucose tolerance were randomized to 30-day treatment with pioglitazone ( 45 mg ) or placebo in addition to optimal medical therapy . All patients in the TZD group showed an increase of adiponectin levels as an indicator of compliance ( 11.4 +/- 1.1 to 36.8 +/- 2.1 microg/ml ; P < 0.001 ) . TZD , but not placebo , decreased mean high-sensitivity C-reactive protein to 43 +/- 19 % ( P < 0.05 ) . Pioglitazone increased CD34 ( + ) /kinase insert domain receptor ( + ) EPCs to 142 +/- 9 % and cultured 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled acetylated LDL ( + ) /lectin ( + ) EPCs to 180 +/- 3 % ( P < 0.05 ) . EPC numbers were not changed in the placebo group . TZD increased the SDF-1-induced migratory capacity to 146 +/- 9 % per EPC number ( P < 0.05 ) and upregulated the clonogenic potential of EPCs , increasing the colony-forming units to 172 +/- 12 % ( P < 0.001 ) . In cultured human EPCs , TZD increased EPC numbers and migration and reduced NADPH-oxidase activity . The TZD effect was reversed by the PPAR gamma antagonist GW9662 and mimicked by treatment with adiponectin . CONCLUSIONS The PPAR gamma agonist pioglitazone increases the number and function of EPCs in patients with coronary artery disease . The effect represents a potential regenerative mechanism in atherosclerosis and is observed in normoglycemic individuals with stable coronary artery disease .
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Intervention_Pharmacological
pioglitazone
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Intervention_Pharmacological
thiazolidinediones [ TZDs ]
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Intervention_Pharmacological
pioglitazone
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Intervention_Pharmacological
pioglitazone
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Intervention_Control
placebo
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Intervention_Physical
in addition to optimal medical therapy
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Intervention_Pharmacological
TZD
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Intervention_Pharmacological
TZD
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Intervention_Control
placebo
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Intervention_Pharmacological
TZD
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Intervention_Pharmacological
TZD
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Intervention_Pharmacological
pioglitazone
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Outcome_Physical
number and function of endothelial progenitor cells
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Outcome_Physical
vascular function
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Outcome_Physical
cardiovascular risk .
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Outcome_Physical
adiponectin levels
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Outcome_Physical
mean high-sensitivity C-reactive protein
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Outcome_Physical
CD34 ( + ) /kinase insert domain receptor ( + ) EPCs
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Outcome_Physical
cultured 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled acetylated LDL ( + ) /lectin ( + ) EPCs
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Outcome_Physical
EPC numbers
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Outcome_Physical
SDF-1-induced migratory capacity
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Outcome_Physical
clonogenic potential of EPCs
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Outcome_Physical
colony-forming units
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Outcome_Physical
EPC numbers and migration and reduced NADPH-oxidase activity .
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Outcome_Physical
number and function of EPCs
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Participant_Condition
patients with documented stable coronary artery disease and normal glucose tolerance .
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Participant_Condition
54 patients with normal fasting glucose levels , 18 showed impaired glucose tolerance and 36 patients with normal glucose tolerance were randomized
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Participant_Condition
normoglycemic individuals with stable coronary artery disease .