Tempol attenuates atherosclerosis associated with metabolic syndrome via decreased vascular inflammation and NADPH-2 oxidase expression

Abstract

Oxidative stress is an important factor in the generation of vascular injury in atherosclerosis. Chronic administration of fructose in rodents is able to facilitate oxidative damage. In the present study we evaluated the role of Tempol, a superoxide dismutase mimetic, on the effect of high fructose intake in apolipoprotein E-deficient (ApoE-KO) mice. Rodents were fed with fructose overload (FF, 10% w/v) for 8 weeks and treated with Tempol 1 mg/kg/day the latest 4 weeks. Tempol revert the pro-oxidant effects caused by FF, diminished lipid peroxidation and impaired vascular NADPH oxidase system through the downregulation of p47phox expression in the vascular wall. Tempol inhibited the expression of vascular adhesion molecule 1 (VCAM-1) in aorta and reduced the development of atheroma plaques. Our results indicate that tempol attenuates oxidative stress by interfering with the correct assembly of Nox2 oxidase complex in the vascular wall and is able to reduce atherosclerosis. Thus tempol represents a potential therapeutic target for preventing risk factors associated with metabolic syndrome.

Keywords::

• NADPH oxidase
• atherosclerosis
• oxidative stress
• tempol

Funding

This work was supported by grant 06/J299 (to C Castro), 2009–2011 from Secretary of Science and Technology, National University of Cuyo, and the National Agency of Scientific and Technological Promotion, Fund for Scientific and Technological Research (FONCyT; PICT 2006-01955, to R Miatello). CB, RA and CA (doctoral fellows) and IQ (post-doctoral fellow) from CONICET.

Acknowledgement

The authors gratefully acknowledge the technical assistance of Mrs. Miriam García.

Declaration of interest

All authors disclose no conflict of interest including any financial, personal, or other relationships with other people or organizations that could inappropriately influence, or be perceived to influence, their work.