J Korean Diabetes Assoc.  2005 Sep;29(5):401-408.

Ascochlorin Derivative, AS-6, Inhibits TNF-alpha-Induced fractalkine, MCP-1 and VCAM-1 Expression in Rat Aortic Smooth Muscle Cells

• Jang YY
• Kim SY
• Kim NK
• Kim MK
• Kim HK
• Kim HS
• Nam CW
• Ryu SY
• Nam SI
• Park KG

Abstract

BACKGOUND: Inflammation is one of the key mechanisms in the development and progression of atherosclerosis. Accumulating evidence suggests that peroxisome proliferators- activated receptorgamma(PPARgamma) plays an important role in the prevention of arterial inflammation and the formation of atherogenesis. This study was designed to evaluate whether the new synthetic PPARgamma, ascochlorin-6(AS-6) has anti-inflammatory and anti-atherogenic effects in primary cultured rat vascular smooth muscle cells(VSMCs).
METHODS
Rat VSMCs were isolated and cultured. Northern and Western blot analyses were performed to evaluate the effects of AS-6 on the expressions of tumor necrosis factor (TNF)-alpha-stimulated fractalkine, monocyte chemoattractant protein(MCP)-1 and vascular cell adhesion molecule (VCAM)-1 in VSMCs. A gel shift assay was performed to examine the mechanism by which AS-6 inhibits the expressions of fractalkine, MCP-1 and VCAM-1.
RESULTS
TNF-alpha markedly induced the expressions of fractalkine, MCP-1 and VCAM-1 in primary cultured VSMCs. AS-6 inhibited the expressions of TNF-alpha-stimulated fractalkine, MCP-1 and VCAM-1 in primary cultured VSMCs. The result of the gel shift assay suggested the inhibitory effects of AS-6 on the expressions of TNF-alpha-stimulated fractalkine, MCP-1 and VCAM-1 were mediated through a nuclear factor kappaB associated pathway.
CONCLUSION
The present study shows that AS-6 has anti-inflammatory effects on VSMCs, suggesting the possibility for the use of AS-6 for prevention of the development and progression of atherosclerosis.

Keyword

Ascochlorin-6; Atherosclerosis; Fractalkine; MCP-1; VCAM-1; Vascular smooth muscle cell

MeSH Terms

Animals
Arteritis
Atherosclerosis
Blotting, Western
Chemokine CX3CL1*
Inflammation
Monocytes
Muscle, Smooth*
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle*
Peroxisomes
PPAR gamma
Rats*
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1*
Chemokine CX3CL1
PPAR gamma
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1