Abstract | OBJECTIVE: METHODS: Human aortic endothelial cells (HAECs) were treated with native- or nanoSOD for 6 h followed by treatment with linoleic acid (LA), a free fatty acid, for 6-24 h. To determine the in vivo relevance, the effectiveness of nanoSOD in reducing vascular cell activation was studied in a mouse model of diet-induced obesity. RESULTS: We noted that nanoSOD was more effectively taken up by ECs than native SOD. Western blot analysis further confirmed that the intracellular accumulation of SOD1 protein was greatly increased upon nanoSOD treatment. Importantly, nanoSOD pretreatment led to a significant decrease in LA-induced oxidative stress in ECs which was associated with a marked increase in SOD enzyme activity in ECs. In vivo studies showed a significant decrease in markers of EC/vascular cell activation and/or inflammation in visceral adipose tissue (VAT), thoracic aorta, and heart collected from nanoSOD-treated mice compared to obese control mice. Interestingly, the expression of metallothionein 2, an antioxidant gene was significantly increased in nanoSOD-treated mice. CONCLUSION: Our data show that nanoSOD is very effective in delivering active SOD to ECs and in reducing EC oxidative stress. Our data also demonstrate that nanoSOD will be a useful tool to reduce vascular cell activation in VAT and aorta in obesity which, in turn, can protect against obesity-associated CVD, in particular, hypertension.
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Authors | Viswanathan Saraswathi, Murali Ganesan, Curtis Perriotte-Olson, Devika S Manickam, Rachel A Westwood, Matthew C Zimmerman, Iman M Ahmad, Cyrus V Desouza, Alexander V Kabanov |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 469
Issue 3
Pg. 495-500
(Jan 15 2016)
ISSN: 1090-2104 [Electronic] United States |
PMID | 26692492
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Free Radical Scavengers
- Nanocapsules
- Superoxide Dismutase
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Topics |
- Animals
- Aortitis
(drug therapy, immunology)
- Cells, Cultured
- Drug Compounding
- Endothelial Cells
(drug effects, immunology)
- Free Radical Scavengers
(administration & dosage)
- Humans
- Mice
- Mice, Inbred C57BL
- Nanocapsules
(administration & dosage, chemistry)
- Obesity
(drug therapy, immunology)
- Superoxide Dismutase
(administration & dosage)
- Treatment Outcome
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