Abstract | BACKGROUND: PRINCIPAL FINDINGS: Intravital microscopy (IVM) of carotid arteries revealed significantly increased L/E-interactions in apolipoproteinE/eNOS double knockout mice (apoE(-/-)/eNOS(-/-)), while P/E-interactions did not differ, compared to apoE(-/-). eNOS deficiency increased macrophage infiltration in carotid arteries and vascular cell adhesion molecule-1 (VCAM-1) expression, both in endothelial and smooth muscle cells. Despite the expression of other NOS isoforms (inducible NOS, iNOS and neuronal NOS, nNOS) in plaques, Electron Spin Resonance (ESR) measurements of NO showed significant contribution of eNOS to total circulating and vascular wall NO production. Pharmacological inhibition and genetic deletion of eNOS reduced vascular superoxide production, indicating uncoupling of the enzyme in apoE(-/-) vessels. CONCLUSION: Overt plaque formation, increased vascular inflammation and L/E- interactions are associated with significant reduction of superoxide production in apoE(-/-)/eNOS(-/-) vessels. Therefore, lack of eNOS does not cause an automatic increase in oxidative stress. Uncoupling of eNOS occurs in apoE(-/-) atherosclerosis but does not negate the enzyme's strong protective effects.
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Authors | Padmapriya Ponnuswamy, Angelika Schröttle, Eva Ostermeier, Sabine Grüner, Paul L Huang, Georg Ertl, Ulrich Hoffmann, Bernhard Nieswandt, Peter J Kuhlencordt |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 1
Pg. e30193
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 22291917
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Apolipoproteins E
- Reactive Oxygen Species
- Superoxides
- Nitric Oxide
- Nitric Oxide Synthase Type III
- Nos3 protein, mouse
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Topics |
- Animals
- Apolipoproteins E
(genetics)
- Atherosclerosis
(enzymology, genetics, metabolism)
- Blood Vessels
(metabolism, pathology)
- Cytoprotection
(genetics)
- Gene Expression Regulation, Enzymologic
(physiology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Nitric Oxide
(metabolism, pharmacology)
- Nitric Oxide Synthase Type III
(genetics, metabolism, physiology)
- Reactive Oxygen Species
(metabolism)
- Superoxides
(metabolism)
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