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Lazaro I, Lopez-Sanz L, Bernal S, et al. Nrf2 Activation Provides Atheroprotection in Diabetic Mice Through Concerted Upregulation of Antioxidant, Anti-inflammatory, and Autophagy Mechanisms. Front Pharmacol. 2018;9:819doi: 10.3389/fphar.2018.00819.
Lazaro, I., Lopez-Sanz, L., Bernal, S., Oguiza, A., Recio, C., Melgar, A., Jimenez-Castilla, L., Egido, J., Madrigal-Matute, J., & Gomez-Guerrero, C. (2018). Nrf2 Activation Provides Atheroprotection in Diabetic Mice Through Concerted Upregulation of Antioxidant, Anti-inflammatory, and Autophagy Mechanisms. Frontiers in pharmacology, 9819. https://doi.org/10.3389/fphar.2018.00819
Lazaro, Iolanda, et al. "Nrf2 Activation Provides Atheroprotection in Diabetic Mice Through Concerted Upregulation of Antioxidant, Anti-inflammatory, and Autophagy Mechanisms." Frontiers in pharmacology vol. 9 (2018): 819. doi: https://doi.org/10.3389/fphar.2018.00819
Lazaro I, Lopez-Sanz L, Bernal S, Oguiza A, Recio C, Melgar A, Jimenez-Castilla L, Egido J, Madrigal-Matute J, Gomez-Guerrero C. Nrf2 Activation Provides Atheroprotection in Diabetic Mice Through Concerted Upregulation of Antioxidant, Anti-inflammatory, and Autophagy Mechanisms. Front Pharmacol. 2018 Jul 31;9:819. doi: 10.3389/fphar.2018.00819. eCollection 2018. PMID: 30108504; PMCID: PMC6080546.
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Front Pharmacol. 2018 Jul 31;9:819. doi: 10.3389/fphar.2018.00819. eCollection 2018.

Nrf2 Activation Provides Atheroprotection in Diabetic Mice Through Concerted Upregulation of Antioxidant, Anti-inflammatory, and Autophagy Mechanisms.

Frontiers in pharmacology

Iolanda Lazaro, Laura Lopez-Sanz, Susana Bernal, Ainhoa Oguiza, Carlota Recio, Ana Melgar, Luna Jimenez-Castilla, Jesus Egido, Julio Madrigal-Matute, Carmen Gomez-Guerrero

Affiliations

  1. Renal, Vascular and Diabetes Research Lab, IIS-Fundacion Jimenez Diaz, Autonoma University of Madrid, Madrid, Spain.
  2. Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, Madrid, Spain.
  3. Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, New York City, NY, United States.

PMID: 30108504 PMCID: PMC6080546 DOI: 10.3389/fphar.2018.00819

Abstract

Interactive relationships between metabolism, inflammation, oxidative stress, and autophagy in the vascular system play a key role in the pathogenesis of diabetic cardiovascular disease. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a stress-sensitive guarantor of cellular homeostasis, which cytoprotective contributions extend beyond the antioxidant defense. We investigated the beneficial effects and underlying mechanisms of the Nrf2 inducer tert-butyl hydroquinone (tBHQ) on diabetes-driven atherosclerosis. In the experimental model of streptozotocin-induced diabetes in apolipoprotein E-deficient mice, treatment with tBHQ increased Nrf2 activity in macrophages and vascular smooth muscle cells within atherosclerotic lesions. Moreover, tBHQ significantly decreased the size, extension and lipid content of atheroma plaques, and attenuated inflammation by reducing lesional macrophages (total number and M1/M2 phenotype balance), foam cell size and chemokine expression. Atheroprotection was accompanied by both systemic and local antioxidant effects, characterized by lower levels of superoxide anion and oxidative DNA marker 8-hydroxy-2'-deoxyguanosine, reduced expression of NADPH oxidase subunits, and increased antioxidant capacity. Interestingly, tBHQ treatment upregulated the gene and protein expression of autophagy-related molecules and also enhanced autophagic flux in diabetic mouse aorta.

Keywords: autophagy; diabetes complications; inflammation; nuclear factor (erythroid-derived 2)-like 2; redox balance

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