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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:514.)
© 2006 American Heart Association, Inc.

Vascular Biology

Elevated Concentrations of Nonesterified Fatty Acids Increase Monocyte Expression of CD11b and Adhesion to Endothelial Cells

Wei-Yang Zhang; Eric Schwartz; Yingjie Wang; Jeanne Attrep; Zhi Li; Peter Reaven

From the Department of Medicine (W.-Y.Z., E.S., Y.W., J.A., P.R.), Section of Endocrinology, Carl T. Hayden Veterans Affairs Medical Center, Phoenix, Ariz; and The Biodesign Institute at Arizona State University (Z.L.), Tempe, Ariz.

Correspondence to Wei-Yang Zhang, Section of Endocrinology, Carl T. Hayden VA Medical Center, Phoenix, AZ 85012. E-mail weiyang.zhang{at}med.va.gov

Objective— Monocyte proinflammatory activity has been demonstrated in obesity, insulin resistance, and type 2 diabetes, metabolic conditions that are frequently associated with elevated levels of nonesterified fatty acids (NEFA). We therefore tested the hypothesis that NEFA may induce monocyte inflammation.

Methods and Results— Monocytes exposed to NEFA for 2 days demonstrated a dose-related increase in intracellular reactive oxygen species (ROS) formation and adhesion to endothelial cells. All of these effects were inhibited by the coaddition of antioxidants such as glutathione or butylated hydroxytoluene, by inhibition of ROS generation by NADPH oxidase inhibitors, and by inhibition of protein kinase C, a recognized stimulator of NAPDH oxidase. Monocytes exposed to NEFA also demonstrated a significant increase in CD11b message expression. Stimulation of monocyte adhesion to endothelial cells by NEFA was inhibited by addition of neutralizing antibodies to either CD11b or CD18. Finally, surface expression of CD11b increased significantly on monocytes as measured by flow cytometry, after their incubation with NEFA.

Conclusion— These studies indicate that elevated concentrations of NEFA may enhance integrin facilitated monocyte adhesion to endothelial cells and these effects appear mediated, in part, through activation of NADPH oxidase and oxidative stress.

This study demonstrates that elevation of NEFA, as frequently occurs in obesity, insulin resistance, and type 2 diabetes, increases monocyte expression of CD11b and adhesion to endothelial cells. These effects appear mediated, in part, through activation of NADPH oxidase and oxidative stress.

Key Words: atherosclerosis • integrins • monocytes • nonesterified fatty acids • reactive oxygen species

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