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En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
Published on: February 25, 2016
Nanoformulated copper/zinc superoxide dismutase attenuates vascular cell activation and aortic inflammation in
Viswanathan Saraswathi1, Murali Ganesan2, Curtis Perriotte-Olson2
1Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, NE, USA; Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA; VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
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.
Insights
Nanoformulated copper/zinc superoxide dismutase (nanoSOD) effectively reduces oxidative stress and inflammation in endothelial cells. This antioxidant therapy shows promise for preventing cardiovascular disease associated with obesity.
Area of Science:
- Biochemistry
- Cell Biology
- Cardiovascular Science
Background:
- Endothelial cell (EC) oxidative stress contributes to vascular dysfunction and cardiovascular disease (CVD).
- Developing effective antioxidant therapies is challenging due to the limited bioavailability of antioxidant enzymes.
- Copper/zinc superoxide dismutase (CuZnSOD or SOD1) is a key antioxidant enzyme.
Purpose of the Study:
- To evaluate the efficacy of nanoformulated SOD1 (nanoSOD) in reducing EC oxidative stress and vascular inflammation in obesity.
- To assess the delivery and activity of nanoSOD in endothelial cells both in vitro and in vivo.
Main Methods:
- Human aortic endothelial cells (HAECs) were treated with native or nanoSOD, followed by linoleic acid (LA) exposure.
- In vivo studies utilized a mouse model of diet-induced obesity to assess nanoSOD's effects on vascular cell activation.
- Western blot and enzyme activity assays were employed to measure SOD1 protein levels and activity.
Main Results:
- NanoSOD demonstrated superior uptake and intracellular accumulation of SOD1 in ECs compared to native SOD.
- NanoSOD treatment significantly reduced LA-induced oxidative stress and increased SOD enzyme activity in ECs.
- In vivo, nanoSOD decreased markers of vascular cell activation and inflammation in visceral adipose tissue, aorta, and heart of obese mice.
Conclusions:
- NanoSOD is an effective tool for delivering active SOD to ECs, significantly reducing EC oxidative stress.
- NanoSOD can mitigate vascular cell activation in obesity, offering potential protection against obesity-associated CVD, including hypertension.
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