FIGURE 10.

Schematic representation of TRC105 effects on human aortic endothelial cells under hypercholesterolemic (treated with 10 μg/ml 7-ketocholesterol [7K] for 12 h) or hyperglycemic (treated with 45 mM high glucose [HG] for 72 h) conditions. Hypercholesterolemia or hyperglycemia stimulates (i) protein expression of Eng, pSmads, vascular cell adhesion molecule 1 (VCAM-1), and P-selectin in endothelial cells; and (ii) monocyte adhesion to endothelial cells and monocyte transmigration through endothelial cell monolayers. The overall effect of hypercholesterolemia or hyperglycemia is endothelial dysfunction (iii). TRC105 inhibits 7K- and HG-induced expression of Eng and pSmads, while enhancing even further expression of VCAM-1 and P-selectin. TRC105 also inhibits 7K- and HG-induced adhesion of monocytes to endothelial cells and transmigration of monocytes through the endothelium, regardless of increased expression of cell adhesion molecules.