Nitric oxide (NO) is generated in endothelial cells by
endothelial NO synthase (eNOS)1,2 and is responsible
for the endothelium-dependent vasorelaxation,3 which is
reduced in arteries from hypercholesterolemic animals and
humans.4,5 Although eNOS was initially considered to be constitutive, it was later demonstrated that cytokines and oxidized LDLs downregulate eNOS expression by destabilizing eNOS mRNA.6,7 In vitro evidence shows that HMG-CoA reductase
inhibitors reverse this downregulation under cholesterolclamped
conditions by stabilizing eNOS mRNA via unknown
mechanisms.8 Sequences controlling mRNA stability have been identified within its 39-untranslated region (39-UTR).9 We recently demonstrated that cultured bovine endothelial cells contain cytosolic proteins that form complexes with the 39-UTR of
eNOS mRNA10 and cause its destabilization,10 thus potentially
leading to endothelial dysfunction. Whether the level of
these proteins is modified in in vivo situations with demonstrated
endothelial dysfunction, ie, hypercholesterolemia,
however, is not established. In this study, we have determined the presence of such proteins and eNOS expression in arteries of hypercholesterolemic rabbits. Because statins prevent endothelial dysfunction and protect eNOS expression in cultured endothelium,8,11 we used cerivastatin, a newly synthesized statin,12 to analyze its actions on these parameters.
Mononuclear cells also produce NO by an eNOS-like
NOS,13 thus opening the possibility that changes in eNOS
could be correlated with modifications in eNOS expression in
mononuclear cells.