Inhibitory effect of troglitazone on TNF-alpha-induced expression of monocyte chemoattractant protein-1 (MCP-1) in...

Insulin resistance is one of the risk factors for the progression of atherosclerosis. Recently, the new oral insulin-sensitizing drug troglitazone is thought to offer potential in the treatment of diabetes. If adopted for such use, this drug might be helpful in protecting against the development of atherosclerosis and microvascular complications via its improvement of insulin resistance. However, it has not yet been clarified whether troglitazone acts directly on the vascular cells and inhibits the progression of atherosclerosis. Meanwhile, Monocyte chemoattractant protein-1 (MCP-1) is known to play an important role in the pathogenesis of atherosclerosis by inducing monocyte migration. Therefore, we investigated the effect of troglitazone on the expression of MCP-1 in human umbilical vein endothelial cells (HUVECs). HUVECs were treated with or without troglitazone (1 or 10 microM) in the presence or absence of various concentrations of tumor necrosis factor-alpha (TNF-alpha) (5, 50 or 500 ng/ml), and then the amounts of MCP-1 secreted from the HUVECs were measured. We found that TNF-alpha increased the secretions of MCP-1 119-fold vs. control, and that troglitazone significantly inhibited this TNF-alpha-induced increase in MCP-1 secretions (19.4%). Moreover, Northern blot analysis revealed that troglitazone decreased the MCP-1 mRNA level in HUVECs. Our present studies indicated that troglitazone may prevent the progression of atherosclerosis by inhibiting MCP-1 expression in endothelial cells.