Changes in markers of vascular injury in response to transient hyperhomocysteinemia

The purpose of this study was to test whether transient increases in homocysteine would promote changes in markers of endothelial injury, cellular fibronectin (cFN), and soluble vascular cell adhesion molecule 1 (sVCAM-1). Homocysteine, cFN, and sVCAM-1 concentrations increased significantly in response to a methionine load by 6 hours in human subjects. However, no correlation was observed between homocysteine and cFN or sVCAM-1. To directly test whether homocysteine can injure endothelial cells, human umbilical vein endothelial cells (HUVEC) were incubated with increasing concentrations of homocysteine, plasma, or serum from hyperhomocysteinemic mice or from the methionine-loaded test subjects. cFN release was increased from endothelial cells cultured with plasma (but not serum) of hyperhomocysteinemic transgenic mice or from methionine-loaded human subjects. These data suggest that very high homocysteine concentrations can promote endothelial injury; however, this effect is likely mediated by secondary effects that include a factor(s) present in plasma that affects endothelial cells.