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Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 8524267, 15 pages
http://dx.doi.org/10.1155/2016/8524267
Research Article

Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells from a Diabetic Rat Model

1Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
2Department of Medicine, Denver VA Medical Center, Denver, CO 80220, USA
3Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
4Department of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
5Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
6Center for Women’s Health Research, University of Colorado School of Medicine, Aurora, CO 80045, USA

Received 18 September 2015; Revised 10 November 2015; Accepted 19 November 2015

Academic Editor: Umesh Yadav

Copyright © 2016 Amy C. Keller et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs) from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK) and the Wistar control rat were exposed to high glucose (25 mM). At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR) were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (). Mitochondrial superoxide increased with high glucose in Wistar SMCs () with no change in the GK beyond elevated baseline concentrations. Baseline comparisons show persistent metabolic perturbations in a diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets.