Abstract
Peroxisome proliferator-activated receptor-alpha (PPAR-α) is a key regulator of lipid and glucose metabolism and has been implicated in inflammation. The vascular effects of activator for PPARs, particularly PPAR-α, 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-γ) secreted in the medium and nuclear factor kappa B (NFκB) 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-γ 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-γ: 98±7, 94±3, 76±8 and 64±8, respectively). NFκB 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.
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