Cited by 67Nitric Oxide and Endothelin EffectsAtherosclerosis and Cardiovascular DiseasesCardiovascular Health and Disease Prevention

Atheroprotective Effects of Neuronal Nitric Oxide Synthase in Apolipoprotein E Knockout Mice

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Kuhlencordt, Peter J., Hötten, Stefanie, Schödel, Johannes, Rützel, Sebastian, Hu, Kai, Widder, Julian, Marx, Alexander, Huang, Paul L. +1 more·2006·Arteriosclerosis, Thrombosis, and Vascular Biology

Abstract

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/nNOSα 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 nNOSα was present in vessels of KO and absent in DKO animals, nNOSγ was expressed in KO and DKO mice. Conclusion— nNOSα protects against atherosclerosis as nNOSα deletion leads to an increase in plaque formation in apoE/nNOSα 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 nNOSα 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.

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Crossref · 10.1161/01.atv.0000223143.88128.19

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Authors
Kuhlencordt, P. J., Hötten, S., Schödel, J., Rützel, S., Hu, K., Widder, J., Marx, A., Huang, P. L., & Ertl, G.
Affiliations
  • Harvard University (US)
  • From Medizinische Klinik I (P.J.K., S.H., J.S., S.R., K.H., J.W., G.E.), Cardiovascular Center and Department of Pathology (A.M.), University Wuerzburg, Germany; Division of Cardiology (P.L.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Published
2006-07
Volume
26
Issue
7
Pages
1539-1544
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
OpenAlex
W2010422806
Cited by
67
References
34
Citations by year
2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 4 · 2013: 5 · 2012: 3
FWCI
2.43
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL057818, HL-57818)
  • National Institute of Neurological Disorders and Stroke (R01NS048426, NS 33335, R01NS033335)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Keywords
neuronal nitric oxide synthase, atherosclerosis, ApoE-deficient mice, atherosclerotic plaque formation, Western diet, blood pressure, neointima, sex differences, atheroprotection
MeSH terms
Animals, Apolipoproteins E, Blood Pressure, Blood Vessels, DNA, Recombinant, Exons, Female, Immunohistochemistry, Male, Mice, Inbred C57BL, Staining and Labeling, Genetic Variation, Tunica Intima, Mice, Knockout, Atherosclerosis, Mice, Nitric Oxide Synthase Type I

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