RGD Reference Report - Atheroprotective effects of neuronal nitric oxide synthase in apolipoprotein e knockout mice. - Rat Genome Database

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Atheroprotective effects of neuronal nitric oxide synthase in apolipoprotein e knockout mice.

Authors: Kuhlencordt, PJ  Hotten, S  Schodel, J  Rutzel, S  Hu, K  Widder, J  Marx, A  Huang, PL  Ertl, G 
Citation: Kuhlencordt PJ, etal., Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1539-44. Epub 2006 Apr 20.
RGD ID: 1642131
Pubmed: PMID:16627802   (View Abstract at PubMed)
PMCID: PMC3845660   (View Article at PubMed Central)
DOI: DOI:10.1161/01.ATV.0000223143.88128.19   (Journal Full-text)

OBJECTIVE: All 3 isoforms of the nitric oxide synthase (NOS) are expressed in atherosclerotic lesions. To test whether neuronal NOS (nNOS) deficiency affects atherosclerosis, we studied apoE/nNOSalpha double knockout (DKO) and apolipoprotein E (apoE) knockout (KO) control mice. METHODS AND RESULTS: Lesion area was significantly increased in male DKO (66%) mice after 14 weeks and in female DKO animals (31%) after 24 weeks of "western" diet. Moreover, mean arterial blood pressure was significantly reduced in female DKO animals. Immunohistochemistry revealed nNOS expression in the neointima of KO mice. In DKO animals, residual nNOS staining was caused by the presence of nNOS splice variants. Whereas nNOSalpha was present in vessels of KO and absent in DKO animals, nNOSgamma was expressed in KO and DKO mice. CONCLUSIONS: nNOSalpha protects against atherosclerosis as nNOSalpha deletion leads to an increase in plaque formation in apoE/nNOSalpha DKO mice. Female DKO mice showed a significant reduction in mean arterial blood pressure. Additionally, we found expression of nNOS splice variants in vessels of apoE KO mice. Our data highlights nNOSalpha overexpression as a potential therapeutic strategy and naturally occurring splice variants that lack exon 2 of the nNOS gene as a potential risk factor for vascular disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
arteriosclerosis  ISONos1 (Mus musculus)1642131; 1642131 RGD 
arteriosclerosis  IAGP 1642131 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos1  (nitric oxide synthase 1)

Genes (Mus musculus)
Nos1  (nitric oxide synthase 1, neuronal)

Genes (Homo sapiens)
NOS1  (nitric oxide synthase 1)


Additional Information