Abstract
Thrombin and other proaggregators have been reported to induce endothelium dependent relaxation in porcine coronary arteries and LDL blocked the relaxation rapidly and reversibly (Tomita et al., Circ. Res. 1990, 66, 18-27). This inhibitory mechanism of LDL was investigated. Lysolecithin acyltransferase (LAT) activity was dose depenedently enhanced by LDL within the range of LDL concentrations in which it exerted an inhibitory effect on the relaxation. This enzyme activity was demonstrated in cultured endothelial cells from porcine aortas, and the activity in the intact cells was profoundly enhanced in the presence of thrombin and LDL in the medium. Heat-treatment (60°, 10min), or acid-treatment (pH 2, 30min at room temp) of LDL, resulted in a complete loss of the stimulatory effect on LAT activity as it caused a loss of LDL-inhibitory effects on the relaxation. In contrast, the DFP-treatment did not alter either of the effects of LDL. Thimerosal (10-8-10-4 M) induced endothelium-dependent relaxation, while the activation by LDL of LAT was blocked in the presence of thimerosal (10-4 M). Thus, the effective deactivation mechanism of LDL inhibition of the endothelium-dependent relaxation coincided well with that for the enhancement of LAT activity. These results suggest that the profound enhancing effect of LDL on LAT activity in the endothelium was possibly involved in the inhibition of endothelium-dependent relaxation by LDL.
