title: Paradoxical reduction of fatty streak formation in mice lacking endothelial nitric oxide synthase.
abstract: BACKGROUND
  The endothelial isoform of nitric oxide synthase (eNOS) has been considered to exert an antiatherosclerotic role through synthesis of NO. However, eNOS has been shown to generate superoxide, which could oxidize LDL and promote atherosclerosis. We sought to determine the role of eNOS in diet-induced fatty streak formation through the use of eNOS-deficient mice.
  
  
  RESULTS
  Mice were fed an atherogenic diet containing 15% fat, 1.25% cholesterol, and 0.5% sodium cholate for 12 weeks, and atherosclerotic lesions at the aortic root were measured after oil-red O staining. Unexpectedly, eNOS-deficient mice developed much smaller aortic lesions than did wild-type control mice (2544+/-1107 versus 7023+/-1569 microm2/section; P=0.03). This reduction in lesion formation could not be explained by changes in plasma levels of lipids and susceptibility of lipoproteins to oxidation. To examine whether eNOS contributed to the oxidation of LDL within the arterial wall, endothelial cells were isolated from the aorta of mice and incubated with native LDL in the absence or presence of N-Omega-nitro-L-arginine methyl ester (L-NAME), a specific NOS inhibitor. L-NAME significantly inhibited LDL oxidation by endothelial cells from wild-type animals (P<0.05), but it had no effect on LDL oxidation by endothelial cells from eNOS-deficient mice.
  
  
  CONCLUSIONS
  These data indicate that absence of eNOS-mediated LDL oxidation may contribute to the reduction of fatty-streak formation in eNOS-deficient mice.
authors: Department of Radiology and Cardiovascular Research Center (W.S.) and Surgery, University of Virginia, Charlottesville, Va, USA.
authors: Weibin
authors: W
authors: Shi
authors: Xuping
authors: X
authors: Wang
authors: Diana M
authors: DM
authors: Shih
authors: Victor E
authors: VE
authors: Laubach
authors: Mohamad
authors: M
authors: Navab
authors: Aldons J
authors: AJ
authors: Lusis
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D002478:Cells, Cultured; D015237:Dinoprost / Q000031:analogs & derivatives*; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
chemical_list: D004791:Enzyme Inhibitors; D028441:F2-Isoprostanes; D008055:Lipids; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D019331:NG-Nitroarginine Methyl Ester