Reduced HMGB 1-Mediated Pathway and Oxidative Stress in Resveratrol-Treated Diabetic Mice: A Possible Mechanism of Cardioprotection of Resveratrol in Diabetes Mellitus.
Myocardial fibrosis and inflammation are intricately linked in diabetic cardiomyopathy (DCM), and resveratrol has been shown to attenuate oxidative stress, inflammation, and fibrosis in several cell types or animal models. High mobility group box 1 (HMGB 1), a proinflammatory cytokine, has been reported to regulate fibrosis and inflammation in various organs. Then the present study aimed to reveal the expression of HMGB 1-mediated signaling pathway and oxidative stress in resveratrol-treated diabetic mice. The significant increase in serum HMGB 1 concentration in diabetic mice was attenuated by treatment with resveratrol. Similarly, western blot analysis revealed a significant increase of HMGB 1 protein in monocytes and heart tissues of diabetic mice, and resveratrol partly normalized the changes. In addition, resveratrol abrogated the increased expression of HMGB 1-mediated signaling pathway, oxidative stress, fibrosis, and inflammation in diabetic hearts. In conclusion, inhibition of HMGB 1-mediated signaling pathway and oxidative stress may contribute to resveratrol-induced anti-inflammatory and antifibrotic effects in DCM.
Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Han
H
Wu
Department of Cardiology, Drum Tower Clinical Medical Hospital, Nanjing Medical University, Nanjing 210008, China; Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.
Zhen-Qiang
ZQ
Sheng
Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Jun
J
Xie
Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Ran
R
Li
Department of Cardiology, Drum Tower Clinical Medical Hospital, Nanjing Medical University, Nanjing 210008, China; Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.
Liang
L
Chen
Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Guan-Nan
GN
Li
Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Lian
0000-0003-1088-7103
L
Wang
Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Biao
0000-0001-7259-298X
B
Xu
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis; D024243:HMGB1 Protein / Q000097:blood*; D006321:Heart / Q000187:drug effects; D007249:Inflammation / Q000517:prevention & control; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1 / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use
D001786:Blood Glucose; D024243:HMGB1 Protein; D008562:Membrane Glycoproteins; D020011:Protective Agents; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013267:Stilbenes; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D000077185:Resveratrol