Oncotarget

Research Papers:

Melatonin attenuated brain death tissue extract-induced cardiac damage by suppressing DAMP signaling

Pei-Hsun Sung, Fan-Yen Lee, Ling-Chun Lin, Kuan-Hung Chen, Hung-Sheng Lin, Pei-Lin Shao, Yi-Chen Li, Yi-Ling Chen, Kun-Chen Lin, Chun-Man Yuen, Hsueh-Wen Chang, Mel S. Lee and Hon-Kan Yip _

PDF  |  HTML  |  How to cite

Oncotarget. 2018; 9:3531-3548. https://doi.org/10.18632/oncotarget.23180

Metrics: PDF 2325 views  |   HTML 2992 views  |   ?  


Abstract

Pei-Hsun Sung1,*, Fan-Yen Lee2,*, Ling-Chun Lin1, Kuan-Hung Chen3, Hung-Sheng Lin4, Pei-Lin Shao5, Yi-Chen Li1, Yi-Ling Chen1, Kun-Chen Lin3, Chun-Man Yuen6, Hsueh-Wen Chang7, Mel S. Lee8 and Hon-Kan Yip1,5,9,10,11

1Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

3Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

4Division of Neurology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

5Department of Nursing, Asia University, Taichung, Taiwan

6Division of Neurosurgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

7Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

8Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

9Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

10Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

11Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

*These authors contributed equally to this work

Correspondence to:

Hon-Kan Yip, email: [email protected]

Keywords: brain death; damage-associated molecular patterns; inflammation; remote organ; heart function

Received: October 02, 2017     Accepted: December 01, 2017     Published: December 12, 2017

ABSTRACT

We tested the hypothesis that melatonin prevents brain death (BD) tissue extract (BDEX)-induced cardiac damage by suppressing inflammatory damage-associated molecular pattern (DAMP) signaling in rats. Six hours after BD induction, levels of a DAMP component (HMGB1) and inflammatory markers (TLR-2, TLR-4, MYD88, IκB, NF-κB, IL-1β, IFN-γ, TNF-α and IL-6) were higher in brain tissue from BD animals than controls. Levels of HMGB1 and inflammatory markers were higher in BDEX-treated H9C2 cardiac myoblasts than in cells treated with healthy brain tissue extract. These increases were attenuated by melatonin but re-induced with luzindole (all P < 0.001). Additional male rats (n = 30) were divided into groups 1 (negative control), 2 (healthy brain tissue extract implanted in the left ventricular myocardium [LVM]), 3 (BDEX-LVM), 4 (BDEX-LVM + melatonin), and 5 (BDEX-LVM + melatonin + luzindole). Collagen deposition/fibrosis and LVM levels of MTR2, HMGB1, inflammatory markers, oxidative stress, apoptosis, mitochondrial damage and DNA damage were highest in group 3, lowest in groups 1 and 2, and higher in group 5 than in group 4. Heart function and LVM levels of MTR1 and anti-inflammatory, mitochondrial-integrity and anti-oxidative markers exhibited a pattern opposite that of the inflammatory markers in the five groups (all P < 0.0001). These results indicate melatonin inhibits BDEX-induced cardiac damage by suppressing the DAMP inflammatory axis.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 23180