PMID- 14691289
OWN - NLM
STAT- MEDLINE
DCOM- 20040114
LR  - 20230216
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 83
IP  - 12
DP  - 2003 Dec
TI  - Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, 
      attenuates myocardial ischemia/reperfusion injury in a rat model.
PG  - 1715-21
AB  - Thiazolidinediones are insulin-sensitizing drugs, ligands for peroxisome 
      proliferator-activated receptor-gamma (PPAR-gamma), which play an important role 
      in the modulation of inflammatory responses. Myocardial ischemia/reperfusion 
      (MI/R) injury is associated with inflammation, in which various cells, 
      particularly monocytes and macrophages, are involved. This study examined the 
      effects of the thiazolidinedione peroxisome proliferator-activated receptor-gamma 
      ligand, pioglitazone, in a rat model of MI/R injury. Pioglitazone at 3 mg/kg/day 
      or the vehicle was administered for 7 days before rats were subjected to 30 
      minutes of coronary ligation followed by 24 hours of reperfusion. The mRNA 
      expression [monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion 
      molecule-1] in the ischemic region, the number of infiltrating macrophages in the 
      ischemic region, and the myocardial infarct size were examined. The inhibitory 
      effects of pioglitazone on activated macrophages were studied in vitro. Phorbol 
      12-myristate 13-acetate-induced MCP-1 production, in the absence or presence of 
      pioglitazone, were assayed in cultured macrophages. Compared with the control 
      group, (1). mRNA levels of MCP-1 and intercellular adhesion molecule-1 and the 
      number of infiltrating macrophages in the ischemic region were significantly 
      lower in the pioglitazone-treated group; and (2). myocardial infarct size was 
      significantly smaller in the pioglitazone-treated group. Phorbol 12-myristate 
      13-acetate-stimulated cultured macrophages in the presence of pioglitazone 
      produced significantly lower levels of MCP-1 than the stimulated control in the 
      absence of pioglitazone. These observations demonstrate that pioglitazone has 
      anti-inflammatory effects in MI/R injury that are independent of its 
      insulin-sensitizing effect.
FAU - Ito, Haruyasu
AU  - Ito H
AD  - The Department of Cardiovascular Medicine, Kyoto University, Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Nakano, Atsushi
AU  - Nakano A
FAU - Kinoshita, Makoto
AU  - Kinoshita M
FAU - Matsumori, Akira
AU  - Matsumori A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transcription Factors)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/genetics/metabolism
MH  - Disease Models, Animal
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Intercellular Adhesion Molecule-1/genetics/metabolism
MH  - Macrophage Activation/drug effects
MH  - Macrophages/drug effects/metabolism
MH  - Male
MH  - Myocardial Infarction/pathology/*prevention & control
MH  - Myocardial Reperfusion Injury/metabolism/pathology/*prevention & control
MH  - Pioglitazone
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Cytoplasmic and Nuclear/*agonists
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Thiazolidinediones/*therapeutic use
MH  - Transcription Factors/*agonists
EDAT- 2003/12/24 05:00
MHDA- 2004/01/15 05:00
CRDT- 2003/12/24 05:00
PHST- 2003/12/24 05:00 [pubmed]
PHST- 2004/01/15 05:00 [medline]
PHST- 2003/12/24 05:00 [entrez]
AID - S0023-6837(22)03424-9 [pii]
AID - 10.1097/01.lab.0000106724.29121.da [doi]
PST - ppublish
SO  - Lab Invest. 2003 Dec;83(12):1715-21. doi: 10.1097/01.lab.0000106724.29121.da.