Sulforaphane attenuation of type 2 diabetes-induced aortic damage was associated with the upregulation of Nrf2 expression and function.
Type 2 diabetes mellitus (T2DM) significantly increases risk for vascular complications. Diabetes-induced aorta pathological changes are predominantly attributed to oxidative stress. Nuclear factor E2-related factor-2 (Nrf2) is a transcription factor orchestrating antioxidant and cytoprotective responses to oxidative stress. Sulforaphane protects against oxidative damage by increasing Nrf2 expression and its downstream target genes. Here we explored the protective effect of sulforaphane on T2DM-induced aortic pathogenic changes in C57BL/6J mice which were fed with high-fat diet for 3 months, followed by a treatment with streptozotocin at 100 mg/kg body weight. Diabetic and nondiabetic mice were randomly divided into groups with and without 4-month sulforaphane treatment. Aorta of T2DM mice exhibited significant increases in the wall thickness and structural derangement, along with significant increases in fibrosis (connective tissue growth factor and transforming growth factor), inflammation (tumor necrosis factor-α and vascular cell adhesion molecule 1), oxidative/nitrative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal), apoptosis, and cell proliferation. However, these pathological changes were significantly attenuated by sulforaphane treatment that was associated with a significant upregulation of Nrf2 expression and function. These results suggest that sulforaphane is able to upregulate aortic Nrf2 expression and function and to protect the aorta from T2DM-induced pathological changes.
Cardiovascular Center at the First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, China ; Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA.
Yonggang
Y
Wang
Cardiovascular Center at the First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, China ; Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA.
Zhiguo
Z
Zhang
Cardiovascular Center at the First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, China.
Wanqing
W
Sun
Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA ; The Chinese-American Research Institute, Wenzhou Medical University, Wenzhou 325035, China ; Departments of Radiation Oncology, Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA.
Yi
Y
Tan
Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA.
Yucheng
Y
Liu
Cardiovascular Center at the First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, China.
Yang
Y
Zheng
Cardiovascular Center at the First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, China.
Quan
Q
Liu
Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA ; The Chinese-American Research Institute, Wenzhou Medical University, Wenzhou 325035, China ; Departments of Radiation Oncology, Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA.
Lu
L
Cai
Cardiovascular Center at the First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, China.
Jian
J
Sun
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005355:Fibrosis; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D017879:Isothiocyanates / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013454:Sulfoxides; D015854:Up-Regulation / Q000187:drug effects*
D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D013454:Sulfoxides; C016766:sulforaphane