Pioglitazone Inhibits LOX-1 Expression in Human Coronary Artery Endothelial Cells by Reducing Intracellular Superoxide Radical Generation

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Abstract
Objective— LOX-1, a novel lectin-like receptor for oxidized LDL (ox-LDL), is expressed in response to ox-LDL, angiotensin II (Ang II), tumor necrosis factor (TNF)-α, and other stress stimuli. It is highly expressed in atherosclerotic tissues. Peroxisome proliferator–activated receptor (PPAR)-γ ligands, such as pioglitazone, exert antiatherosclerotic effects. This study examined the regulation of LOX-1 expression in human coronary artery endothelial cells (HCAECs) by pioglitazone. Methods and Results— Fourth generation HCAECs were treated with ox-LDL, Ang II, or TNF-α with or without pioglitazone pretreatment. All 3 stimuli upregulated LOX-1 expression (mRNA and protein). Pioglitazone, in a concentration-dependent manner, reduced LOX-1 expression ( P P P Conclusions— These observations suggest that the PPAR-γ ligand pioglitazone reduces intracellular superoxide radical generation and subsequently reduces the expression of transcription factors, expression of the LOX-1 gene, and monocyte adhesion to activated endothelium. The salutary effect of PPAR-γ ligands in atherogenesis may involve the inhibition of LOX-1 and the adhesion of monocytes to endothelium.

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