PMID- 12411463
OWN - NLM
STAT- MEDLINE
DCOM- 20021108
LR  - 20190722
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 40
IP  - 5
DP  - 2002 Nov
TI  - Antiinflammatory and antiarteriosclerotic effects of pioglitazone.
PG  - 687-93
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands are widely 
      used in patients with insulin resistance and diabetes. Because coronary artery 
      disease is a major complication for such patients, it is important to determine 
      the effects of PPARgamma activation on arteriosclerosis. Long-term inhibition of 
      endothelial NO synthesis by administration of N(omega)-nitro-L-arginine methyl 
      ester (L-NAME) to rats induces coronary vascular inflammation (monocyte 
      infiltration, monocyte chemoattractant protein-1 [MCP-1] expression) and 
      subsequent arteriosclerosis. We examined the effects of pioglitazone (a PPARgamma 
      ligand) in this rat model to determine whether PPARgamma activation with 
      pioglitazone inhibits arteriosclerosis by its indirect effects on metabolic 
      conditions or by direct effects on the cells participating to the pathogenesis of 
      arteriosclerosis. We found that pioglitazone did not affect metabolic states, 
      systolic blood pressure, or serum NO levels, but did prevent the L-NAME-induced 
      coronary inflammation and arteriosclerosis. Pioglitazone did not reduce local 
      expression of MCP-1 but markedly attenuated increased expression of the MCP-1 
      receptor C-C chemokine receptor 2 (CCR2) in lesional and circulating monocytes. 
      PPARgamma activation with pioglitazone prevented coronary arteriosclerosis, 
      possibly by its antiinflammatory effects (downregulation of CCR2 in circulating 
      monocytes). Inhibition of the CCR2-mediated inflammation may represent novel 
      antiinflammatory actions of pioglitazone beyond improvement of metabolic state.
FAU - Ishibashi, Minako
AU  - Ishibashi M
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyushu 
      University, Fukuoka, Japan.
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Hiasa, Ken-ichi
AU  - Hiasa K
FAU - Inoue, Shujiro
AU  - Inoue S
FAU - Ni, Weihua
AU  - Ni W
FAU - Zhao, Qingwei
AU  - Zhao Q
FAU - Usui, Makoto
AU  - Usui M
FAU - Kitamoto, Shiro
AU  - Kitamoto S
FAU - Ichiki, Toshihiro
AU  - Ichiki T
FAU - Takeshita, Akira
AU  - Takeshita A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Blood Glucose)
RN  - 0 (Ccr2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Insulin)
RN  - 0 (Lipids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Arteriosclerosis/chemically induced/metabolism/pathology/*prevention & control
MH  - Blood Glucose/drug effects
MH  - Blood Pressure/drug effects
MH  - Chemokine CCL2/genetics/metabolism
MH  - Coronary Artery Disease/chemically induced/metabolism/pathology/prevention & 
      control
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Inflammation/chemically induced/metabolism/pathology/*prevention & control
MH  - Insulin/blood
MH  - Lipids/blood
MH  - Male
MH  - Monocytes/drug effects/metabolism/pathology
MH  - Myocardium/metabolism
MH  - NG-Nitroarginine Methyl Ester
MH  - Nitric Oxide Synthase/antagonists & inhibitors
MH  - Nitric Oxide Synthase Type III
MH  - Peptidyl-Dipeptidase A/metabolism
MH  - Pioglitazone
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/drug effects/metabolism
MH  - Thiazoles/*pharmacology
MH  - *Thiazolidinediones
MH  - Transcription Factors/drug effects/metabolism
MH  - Transforming Growth Factor beta/genetics/metabolism
MH  - Transforming Growth Factor beta1
MH  - Treatment Outcome
EDAT- 2002/11/02 04:00
MHDA- 2002/11/26 04:00
CRDT- 2002/11/02 04:00
PHST- 2002/11/02 04:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/11/02 04:00 [entrez]
AID - 10.1161/01.hyp.0000036396.64769.c2 [doi]
PST - ppublish
SO  - Hypertension. 2002 Nov;40(5):687-93. doi: 10.1161/01.hyp.0000036396.64769.c2.