PMID- 17068283
OWN - NLM
STAT- MEDLINE
DCOM- 20070122
LR  - 20181201
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 27
IP  - 1
DP  - 2007 Jan
TI  - Pioglitazone inhibits in-stent restenosis in atherosclerotic rabbits by targeting 
      transforming growth factor-beta and MCP-1.
PG  - 182-9
AB  - OBJECTIVE: Although emerging data from preclinical and clinical studies suggests 
      a reduction of in-stent restenosis with peroxisome proliferator-activated 
      receptor (PPAR)-gamma agonists, the reduction of neointimal growth via 
      anti-inflammatory mechanisms has not been explored. METHODS AND RESULTS: 
      Hypercholesterolemic New Zealand White rabbits (n=45) received bilateral 
      balloon-expandable stents implanted into atherosclerotic iliac arteries. Animals 
      were randomized to oral pioglitazone 3 (low dose) or 10 mg/kg per day (high dose) 
      started on the day of stent implantation; control rabbits received placebo. 
      Tissue harvest was performed 28 days after stenting, and stented segments 
      underwent histology, morphometry, immunostaining for macrophages, and scanning 
      electron microscopy. In selected animals, stented arterial segments were placed 
      in organoid culture for 48 hours, and the conditioned media was assayed for 23 
      different cytokines. There was a 21% reduction in neointimal area for high-dose 
      pioglitazone treated versus placebo rabbits (P<0.005), which was associated with 
      a significant reduction of neointimal macrophages. Analysis of conditioned media 
      revealed an 82% and 74% reduction in the release of monocyte chemoattractant 
      protein-1 (MCP-1) (P<0.007) and transforming growth factor (TGF)-beta1 (P<0.01), 
      respectively, in stented segments from animals treated with 10 mg/kg per day 
      pioglitazone versus placebo. CONCLUSIONS: Oral pioglitazone suppresses in-stent 
      neointimal growth by limiting local inflammatory pathways and may be useful as an 
      adjunctive therapy in patients undergoing percutaneous interventions.
FAU - Joner, Michael
AU  - Joner M
AD  - CVPath Institute Inc, Gaithersburg, MD 20878, USA.
FAU - Farb, Andrew
AU  - Farb A
FAU - Cheng, Qi
AU  - Cheng Q
FAU - Finn, Aloke V
AU  - Finn AV
FAU - Acampado, Eduardo
AU  - Acampado E
FAU - Burke, Allen P
AU  - Burke AP
FAU - Skorija, Kristi
AU  - Skorija K
FAU - Creighton, Wendy
AU  - Creighton W
FAU - Kolodgie, Frank D
AU  - Kolodgie FD
FAU - Gold, Herman K
AU  - Gold HK
FAU - Virmani, Renu
AU  - Virmani R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061026
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transforming Growth Factor beta)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Atherosclerosis/*drug therapy/metabolism/pathology/physiopathology
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Coronary Restenosis/etiology/metabolism/physiopathology/*prevention & control
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation/drug effects
MH  - Hypoglycemic Agents/administration & dosage/pharmacology/*therapeutic use
MH  - Macrophages/metabolism
MH  - Mice
MH  - Organ Culture Techniques
MH  - Pioglitazone
MH  - Rabbits
MH  - Random Allocation
MH  - *Stents
MH  - Thiazolidinediones/administration & dosage/pharmacology/*therapeutic use
MH  - Transforming Growth Factor beta/genetics/*metabolism
MH  - Tunica Intima/drug effects/pathology
EDAT- 2006/10/28 09:00
MHDA- 2007/01/24 09:00
CRDT- 2006/10/28 09:00
PHST- 2006/10/28 09:00 [pubmed]
PHST- 2007/01/24 09:00 [medline]
PHST- 2006/10/28 09:00 [entrez]
AID - 01.ATV.0000251021.28725.e8 [pii]
AID - 10.1161/01.ATV.0000251021.28725.e8 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):182-9. doi: 
      10.1161/01.ATV.0000251021.28725.e8. Epub 2006 Oct 26.