抄録
Nitric oxide (NO) is a bioactive molecule for leukocyte, endothelial cells of blood vessels and neurons. NO is generated from L-arginine by the action of NO synthase (NOS). Endothelial NOS (eNOS) was phosphorylated by protein kinase C (PKC) and protein kinase A. Phosphorylation of eNOS by PKC reduced the NOS activity. eNOS mRNA is constitutively expressed in endothelial cells and regulated by intracellular Ca2+ concentration. To examine the regulation of eNOS mRNA by cytokines, atherogenic lipids and mechanical stretch, we employed RNase protection assay and Western blotting in cultured bovine aortic endothelial cells. Interferon α/β upregulates eNOS mRNA expression in a transcriptional level. Moreover, mechanical stretch upregulated eNOS mRNA expression and NO production. TNF-α downregulated eNOS mRNA through destabilization of mRNA. In atherosclerotic arteries endothelium-dependent relaxation (EDR) is impaired. To clarify the mechanisms of impaired EDR, we investigated the effect oxidized LDL on EDR. Fractionation of individual lipids revealed that lysophosphatidylcholine (LPC) inhibited EDR. OX-LDL or LPC inhibited accumulation of IP3 followed by the increase of intracellular Ca2+ concentration induced by agonists including bradykinin. On the other hand, atherogenic lipidsuch as oxidized LDL and lysiphosphatidylcholine increased eNOS mRNA and protein. From these results, LPC in ox-LDL may cause the impairment of EDR in atherosclerotic arteries.
