Impairment of Coronary Graft Vascular Endothelium---Role of Hypoxia and Hemoglobulin

Considerable evidence indicates that impaired endothelial-derived NO (EDNO) bioactivity during vascular diseases is due to excess vascular oxidative stress. Impaired blood vessels produce increased amounts of reactive oxygen species (ROS), derived primarily from endothelial cells and detected principally as superoxide anion (•O2 -) radical and its dismutation product hydrogen peroxide (H2O2). Superoxide interacts readily with NO to limit EDNO bioactivity in believed to hinder the coronary graft potency after open heart surgery. In modern open heart surgery, a certain amount of whole blood is usually added during coronary graft preservation. Reasonably, a significant amount of red blood cells (RBC) may have been lysed under hypoxic condition at room temperature, resulting in large amounts of free heme release, i.e., hemolysis. When coronary graft under the hypoxic condition and hypoxia-induced RBC lysis as been routinely applied in modern open heart surgery, the concept of coronary graft protection prior to the open heart surgery is challenged and need to have further studies. To challenge and investigate the conventional strategy of coronary graft preservation prior to open hear surgery (i.e., certain amount of whole blood is usually added under hypoxia condition), in the present three-year proposal, we will mimic the vascular physiology of vascular endothelial cell (i.e., HUVE-12) and vascular smooth cell (i.e., HUVS) in our coculture system to evaluate the potential effectiveness of exogenous supplementation of NO precursor, L-arginine and antioxidant, glutathione in amelioration of hypoxia-induced vascular impairment.

Project ID:PC9709-0455
External Project ID:NSC97-2314-B182-012-MY3