Background: Lysophosphatidylcholine (LPC) is a product of phosphatidylcholine hydrolysis by phospholipase A(2) and a mediator of the lipid-induced atherosclerotic changes. In this study, we determined the effects of LPC on vasomotor functions, oxidative stress, and endothelial nitric oxide synthase (eNOS) expression in porcine coronary arteries.
Methods: Porcine coronary arteries were cut into 5-mm rings and were treated with LPC or antioxidant selenomethionine (SeMet). For the vasomotor studies, we used a myograph tension system. Levels of superoxide anion (O(2)(-)) were detected by the lucigenin-enhanced chemiluminescence method. The eNOS protein level was studied by immunohistochemistry with avidin-biotin complex immunoperoxidase procedure.
Results: Endothelium-dependent relaxation in response to bradykinin was reduced by 36% and 81% for the rings treated with 12.5 and 25 mum of LPC, respectively, as compared with controls (P < 0.05). Endothelium-independent relaxation in response to sodium nitroprusside also was reduced by 63% after treatment with 25 mum LPC (P < 0.05). The O(2)(-) level was increased in the porcine arteries treated with 25 mum of LPC by 41% as compared with controls (P < 0.05). The antioxidant SeMet reversed the effects of LPC on vascular relaxation and O(2)(-) production. Immunoreactivity of eNOS in LPC-treated vessel rings also was reduced substantially.
Conclusions: LPC impairs endothelium-dependent and endothelium-independent vasorelaxation. This effect is associated with increased superoxide radical production and decreased eNOS activity and is practically reversed with the use of the antioxidant SeMet.