Korean J Physiol Pharmacol.  2005 Apr;9(2):109-115.

Enhanced Expression of Cell Adhesion Molecules in the Aorta of Diabetic Mice is Mediated by gp91phox-derived Superoxide

• Yun MR
• Kim JJ
• Lee SM
• Heo HJ
• Bae SS
• Kim CD

Abstract

Endothelial activation and subsequent recruitment of inflammatory cells are important steps in atherogenesis. The increased levels of cell adhesion molecules (CAM) have been identified in diabetic vasculatures, but the underlying mechanisms remain unclear. To determine the relationship among vascular production of superoxide, expression of CAM and diabetes, superoxide generation and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E- and P-selectin in the aorta from control (C57BL/6J) and diabetic mice (ob/ob) were measured. In situ staining for superoxide using dihydroethidium showed an increased superoxide production in diabetic aorta, accompanied with an enhanced NAD (P) H oxidase activity. Immunohistochemical analysis revealed that the endothelial expression of ICAM-1 (3.5+/-0.4) and VCAM-1 (3.8+/-0.3) in diabetic aorta was significantly higher than those in control aorta (0.9+/-0.5 and 1.6+/-0.3, respectively), accompanied with the enhanced expression of gp91phox, a membrane subunit of NAD (P) H oixdase. Furthermore, there was a strong positive correlation (r=0.89, P< 0.01 in ICAM-1 and r=0.88, P< 0.01 in VCAM-1) between ICAM-1/VCAM-1 expression and vascular production of superoxide. The present data indicate that the increased production of superoxide via NAD (P) H oxidase may explain the enhanced expression of CAM in diabetic vasculatures.

Keyword

Diabetes; ICAM-1; VCAM-1; E-selectin; NAD (P) H oxidase

MeSH Terms

Animals
Aorta*
Atherosclerosis
Cell Adhesion Molecules*
Cell Adhesion*
E-Selectin
Intercellular Adhesion Molecule-1
Membranes
Mice*
NAD
Oxidoreductases
P-Selectin
Superoxides*
Vascular Cell Adhesion Molecule-1
Cell Adhesion Molecules
E-Selectin
Intercellular Adhesion Molecule-1
NAD
Oxidoreductases
P-Selectin
Superoxides
Vascular Cell Adhesion Molecule-1