Newly Developed PPAR-alpha Agonist (R)-K-13675 Inhibits the Secretion of Inflammatory Markers Without Affecting Cell Proliferation or Tube Formation

Atherosclerosis. 2009 Mar;203(1):75-81. doi: 10.1016/j.atherosclerosis.2008.05.055. Epub 2008 Jun 6.


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.

MeSH terms

  • Atherosclerosis / metabolism
  • Benzoxazoles / pharmacology*
  • Biological Transport
  • Butyrates / pharmacology*
  • Cell Proliferation
  • Cells, Cultured
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL5 / metabolism
  • Collagen / chemistry
  • Drug Combinations
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Inflammation
  • Interferon-gamma / biosynthesis
  • Interleukin-6 / biosynthesis
  • Laminin / chemistry
  • NF-kappa B / metabolism
  • PPAR alpha / agonists*
  • Proteoglycans / chemistry


  • (R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid
  • Benzoxazoles
  • Butyrates
  • Chemokine CCL2
  • Chemokine CCL5
  • Drug Combinations
  • Interleukin-6
  • Laminin
  • NF-kappa B
  • PPAR alpha
  • Proteoglycans
  • matrigel
  • Interferon-gamma
  • Collagen