LOW CONCENTRATION OF OXIDIZED LOW-DENSITY-LIPOPROTEIN AND LYSOPHOSPHATIDYLCHOLINE UP-REGULATE CONSTITUTIVE NITRIC-OXIDE SYNTHASE MESSENGER-RNA EXPRESSION IN BOVINE AORTIC ENDOTHELIAL-CELLS

Endothelium-dependent relaxation is markedly reduced in atheroscleroti c arteries. Recently, the endothelium-dependent relaxing factor has be en identified as nitric oxide (NO). We used RNase protection assay and immunoblotting to elucidate the effect of atherogenic lipoprotein on the expression of constitutive NO synthase (cNOS) mRNA and protein lev els in bovine aortic endothelial cells. Twenty-four-hour exposure to a low concentration of oxidized low-density lipoprotein (10 mu g protei n/mL) upregulated cNOS mRNA levels (2.4+/-0.4-fold, P<.01). However, n ative low-density lipoprotein and high-density lipoprotein did not hav e any effect on cNOS mRNA levels. Furthermore, 5 mu g/mL of lysophosph atidylcholine (LPC) also upregulated cNOS mRNA levels (2.6+/-0.5-fold, P<.01) at 8 hours. This action of LPC was abolished with cycloheximid e but not with staurosporine. We concluded that atherogenic lipoprotei ns upregulate cNOS mRNA and protein levels in bovine aortic endothelia l cells. This observation supports the hypothesis that an impairment o f endotherium-dependent vasodilatation in atherosclerotic vessels may not be due to a decrease in cNOS expression. Moreover, the LPC action on cNOS mRNA levels requires new protein synthesis.