PMID- 15585194
OWN - NLM
STAT- MEDLINE
DCOM- 20050418
LR  - 20121115
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 178
IP  - 1
DP  - 2005 Jan
TI  - A potent activator of PPARalpha and gamma reduces the vascular cell recruitment 
      and inhibits the intimal thickning in hypercholesterolemic rabbits.
PG  - 1-7
AB  - Peroxisome proliferator-activated receptors (PPARs) regulate the vascular cell 
      functions as well as systemic lipid and glucose metabolism. Here, we studied the 
      effect of TAK-559, a newly developed potent activator both for PPARalpha and 
      gamma, on the vascular cell recruitment. TNF-alpha- or interleukin-1beta 
      (IL-1beta)-induced THP-1 cell attachment to cultured endothelial cells was 
      significantly reduced in the presence of 10 microM TAK-559 (P < 0.05). The 
      secretion of monocyte chemoattractant protein-1 (MCP-1) from endothelial cells is 
      reduced by 36% in the presence of 10 microM TAK-559, accompanied with the 
      decreased mRNA expression in the cells. The proliferation and migration of 
      cultured smooth muscle cells (SMCs) were significantly decreased in the presence 
      of TAK-559 (P < 0.05). TAK-559-treated hypercholesterolemic rabbits showed the 
      significant reduction of intimal thickning after balloon catheterization by 51% 
      compared with control (P < 0.05), although the plasma lipid and glucose level was 
      not changed between them. The numbers of macrophage and SMCs were decreased to 
      34% and 49% in the hyperplastic intima of arteries from TAK-559-treated rabbits 
      compared to those from control, respectively. These results suggest that the 
      PPARalpha and gamma activator inhibits the recruitment of macrophages and SMCs in 
      intima, possibly leading to the reduction of intimal hyperplasia in 
      hypercholesterolemia.
FAU - Seki, Naoto
AU  - Seki N
AD  - Department of Clinical Cell Biology (F5), Graduate School of Medicine, Chiba 
      University, Chiba 260-8670, Japan.
FAU - Bujo, Hideaki
AU  - Bujo H
FAU - Jiang, Meizi
AU  - Jiang M
FAU - Shibasaki, Manabu
AU  - Shibasaki M
FAU - Takahashi, Kazuo
AU  - Takahashi K
FAU - Hashimoto, Naotake
AU  - Hashimoto N
FAU - Saito, Yasushi
AU  - Saito Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 
      ((E)-4-(4-((5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy)benzyloxyimino)-4-phenylbutyric 
      acid)
RN  - 0 (Butyrates)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Oxazoles)
RN  - 0 (PPAR alpha)
RN  - 0 (PPAR gamma)
SB  - IM
MH  - Animals
MH  - Blood Vessels/drug effects/*pathology
MH  - Butyrates/*pharmacology
MH  - Carotid Arteries/pathology
MH  - Cell Adhesion
MH  - Cell Division/drug effects
MH  - Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/antagonists & inhibitors
MH  - Endothelial Cells/metabolism
MH  - Humans
MH  - Hypercholesterolemia/*pathology
MH  - Hyperplasia
MH  - Macrophages/pathology
MH  - Muscle, Smooth, Vascular/pathology
MH  - Myocytes, Smooth Muscle/pathology
MH  - Oxazoles/*pharmacology
MH  - PPAR alpha/*drug effects
MH  - PPAR gamma/*drug effects
MH  - Rabbits
MH  - Tunica Intima/drug effects/*pathology
EDAT- 2004/12/09 09:00
MHDA- 2005/04/19 09:00
CRDT- 2004/12/09 09:00
PHST- 2004/02/15 00:00 [received]
PHST- 2004/07/18 00:00 [revised]
PHST- 2004/08/10 00:00 [accepted]
PHST- 2004/12/09 09:00 [pubmed]
PHST- 2005/04/19 09:00 [medline]
PHST- 2004/12/09 09:00 [entrez]
AID - S0021-9150(04)00410-1 [pii]
AID - 10.1016/j.atherosclerosis.2004.08.015 [doi]
PST - ppublish
SO  - Atherosclerosis. 2005 Jan;178(1):1-7. doi: 10.1016/j.atherosclerosis.2004.08.015.