Nanoformulated copper/zinc superoxide dismutase attenuates vascular cell activation and aortic inflammation in obesity

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

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Objective Endothelial cell (EC) oxidative stress can lead to vascular dysfunction which is an underlying event in the development of cardiovascular disease (CVD). The lack of a potent and bioavailable anti-oxidant enzyme is a major challenge in studies on antioxidant therapy. The objective of this study is to determine whether copper/zinc superoxide dismutase (CuZnSOD or SOD1) after nanoformulation (nanoSOD) can effectively reduce EC oxidative stress and/or vascular inflammation in obesity. 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.

Original languageEnglish (US)
Pages (from-to)495-500
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume469
Issue number3
DOIs
StatePublished - Jan 15 2016

Keywords

  • Free fatty acid
  • NanoSOD
  • Obesity
  • Oxidative stress
  • Superoxide dismutase
  • Vascular inflammation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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