PMID- 18606415
OWN - NLM
STAT- MEDLINE
DCOM- 20090909
LR  - 20121115
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 203
IP  - 1
DP  - 2009 Mar
TI  - Newly developed PPAR-alpha agonist (R)-K-13675 inhibits the secretion of 
      inflammatory markers without affecting cell proliferation or tube formation.
PG  - 75-81
LID - 10.1016/j.atherosclerosis.2008.05.055 [doi]
AB  - Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a key regulator 
      of lipid and glucose metabolism and has been implicated in inflammation. The 
      vascular effects of activator for PPARs, particularly PPAR-alpha, on vascular 
      cells remain to be fully elucidated. Therefore, we analyzed the hypothesis that 
      newly developed (R)-K-13675 decreases the secretion of inflammatory markers 
      without affecting cell proliferation or tube formation. Human coronary 
      endothelial cells (HCECs) were maintained in different doses of (R)-K-13675 under 
      serum starvation. After 20h, the levels of monocyte chemoattractant protein-1 
      (MCP-1), regulated on activation, normal T expressed and secreted (RANTES), 
      interleukin-6 (IL-6) and interferon-gamma (INF-gamma) secreted in the medium and 
      nuclear factor kappa B (NFkappaB) in cell lysate were analyzed using 
      enzyme-linked immunosorbent assays (ELISA). Upon treatment with (R)-K-13675 at 0, 
      10, 20, 50 and 100nM, with the inflammatory markers at 0nM as 100 (arbitrary 
      units), MCP-1 levels were significantly suppressed (94+/-9, 88+/-2, 80+/-5 and 
      74+/-11, respectively). RANTES, IL-6 and INF-gamma levels were also significantly 
      suppressed (RANTES: 92+/-2, 74+/-9, 64+/-7 and 60+/-2, respectively, IL-6: 
      97+/-2, 89+/-10, 82+/-1 and 66+/-7, respectively, INF-gamma: 98+/-7, 94+/-3, 
      76+/-8 and 64+/-8, respectively). NFkappaB levels were also decreased to 91+/-5, 
      90+/-5, 84+/-7 and 82+/-8, respectively. In addition, (R)-K-13675 did not affect 
      HCEC proliferation or tube formation at up to 100nM. Thus, (R)-K-13675 was 
      associated with the inhibition of inflammatory responses without affecting cell 
      proliferation or angiogenesis, and subsequently may induce an 
      anti-atherosclerotic effect.
FAU - Kitajima, Ken
AU  - Kitajima K
AD  - Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, 
      Jonan-ku, Fukuoka 814-0180, Japan.
FAU - Miura, Shin-Ichiro
AU  - Miura S
FAU - Mastuo, Yoshino
AU  - Mastuo Y
FAU - Uehara, Yoshinari
AU  - Uehara Y
FAU - Saku, Keijiro
AU  - Saku K
LA  - eng
PT  - Journal Article
DEP - 20080606
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 ((R)-2-(3-((benzoxazol-2-yl-d4 
      (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid)
RN  - 0 (Benzoxazoles)
RN  - 0 (Butyrates)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Drug Combinations)
RN  - 0 (Interleukin-6)
RN  - 0 (Laminin)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR alpha)
RN  - 0 (Proteoglycans)
RN  - 119978-18-6 (matrigel)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Atherosclerosis/metabolism
MH  - Benzoxazoles/*pharmacology
MH  - Biological Transport
MH  - Butyrates/*pharmacology
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis
MH  - Chemokine CCL5/metabolism
MH  - Collagen/chemistry
MH  - Drug Combinations
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Inflammation
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-6/biosynthesis
MH  - Laminin/chemistry
MH  - NF-kappa B/metabolism
MH  - PPAR alpha/*agonists
MH  - Proteoglycans/chemistry
EDAT- 2008/07/09 09:00
MHDA- 2009/09/10 06:00
CRDT- 2008/07/09 09:00
PHST- 2007/11/13 00:00 [received]
PHST- 2008/05/22 00:00 [revised]
PHST- 2008/05/29 00:00 [accepted]
PHST- 2008/07/09 09:00 [pubmed]
PHST- 2009/09/10 06:00 [medline]
PHST- 2008/07/09 09:00 [entrez]
AID - S0021-9150(08)00387-0 [pii]
AID - 10.1016/j.atherosclerosis.2008.05.055 [doi]
PST - ppublish
SO  - Atherosclerosis. 2009 Mar;203(1):75-81. doi: 
      10.1016/j.atherosclerosis.2008.05.055. Epub 2008 Jun 6.