Abstract
Objective:
To investigate the mechanistic basis underlying antirestenosis and the antiatherogenic effect of pioglitazone in patients with type 2 diabetes mellitus who were undergoing zotarolimus-eluting stent implantation.
Methods and results:
Recent studies highlight the beneficial effect of pioglitazone in attenuating neointimal growth after stent implantation. Patients with coronary artery diseases were randomly assigned to pioglitazone (n=47) or placebo (n=47) after stent implantation. Pioglitazone significantly reduced neointimal hyperplasia within the stented lesion and attenuated total plaque burden in the in-segment regions of the stent, as assessed by intravascular ultrasonography at the 8-month follow-up. These changes were preceded by reduced circulating natural killer (NK) cells, diminished interleukin 6 and monocyte chemoattractant protein-1 levels, and downregulation of chemokine receptor 2 at 2 days after stent implantation; and an elevated interleukin 10 level at 10 days after implantation. Furthermore, the proliferation and migration of vascular smooth muscle cells were inhibited in the presence of pioglitazone-treated patient serum, demonstrating that the antiproliferative effects of pioglitazone occurred concurrently with its antiinflammatory action.
Conclusions:
Our data present early cellular and immunologic changes by pioglitazone that might have been associated with antirestenotic and antiatherogenic effects in diabetic patients. Inhibiting proinflammatory responses while promoting antiinflammatory circuits, together with an antiproliferative action, may, in part, account for the antirestenotic effect of pioglitazone by altering vascular remodeling processes in the early phase.
Publication types
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Angioplasty, Balloon, Coronary / adverse effects
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Angioplasty, Balloon, Coronary / instrumentation*
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Biomarkers / blood
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Blood Glucose / metabolism
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Cardiovascular Agents / administration & dosage*
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Cell Movement / drug effects
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Cell Proliferation / drug effects*
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Cells, Cultured
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Chemokine CCL2 / blood
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Coronary Angiography
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Coronary Artery Disease / blood
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Coronary Artery Disease / complications
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Coronary Artery Disease / diagnosis
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Coronary Artery Disease / immunology
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Coronary Artery Disease / therapy*
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Coronary Restenosis / etiology
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Coronary Restenosis / prevention & control
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Coronary Vessels / diagnostic imaging
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Coronary Vessels / drug effects*
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Coronary Vessels / immunology
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Diabetes Mellitus, Type 2 / blood
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Diabetes Mellitus, Type 2 / complications
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Diabetes Mellitus, Type 2 / drug therapy*
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Diabetes Mellitus, Type 2 / immunology
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Dose-Response Relationship, Drug
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Drug-Eluting Stents*
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Female
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Glycated Hemoglobin / metabolism
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Humans
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Hyperplasia
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Hypoglycemic Agents / therapeutic use*
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Inflammation Mediators / blood
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Insulin / blood
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Interleukin-6 / blood
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology
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Lipids / blood
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Male
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Middle Aged
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Myocytes, Smooth Muscle / drug effects
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Myocytes, Smooth Muscle / pathology
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Pioglitazone
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Prospective Studies
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Prosthesis Design
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Receptors, CCR2 / blood
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Republic of Korea
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Single-Blind Method
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Sirolimus / administration & dosage
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Sirolimus / analogs & derivatives*
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Thiazolidinediones / therapeutic use*
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Time Factors
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Treatment Outcome
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Tunica Intima / diagnostic imaging
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Tunica Intima / drug effects*
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Tunica Intima / immunology
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Ultrasonography, Interventional
Substances
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Biomarkers
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Blood Glucose
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CCL2 protein, human
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CCR2 protein, human
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Cardiovascular Agents
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Chemokine CCL2
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Glycated Hemoglobin A
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Hypoglycemic Agents
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IL6 protein, human
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Inflammation Mediators
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Insulin
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Interleukin-6
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Lipids
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Receptors, CCR2
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Thiazolidinediones
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hemoglobin A1c protein, human
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zotarolimus
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Sirolimus
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Pioglitazone