Hongwen Lan1, Yunshu Su1, Yakun Liu1, Cheng Deng2, Jing Wang1, Taiqiang Chen1, Kouevidjin Ekue Dodzi Jules1, Jackson Ferdinand Masau1, Huiling Li2, Xiang Wei3. 1. Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. Department of Ultrasonography, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Hubei Provincial Key Laboratory of Molecular Imaging, Wuhan, China. 3. Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: xiangwei@tjh.tjmu.edu.cn.
Abstract
AIMS: The shortage of donor hearts could be alleviated with the use of the allografts from donation after circulatory death (DCD). Here, we evaluated the protective effect of melatonin on myocardial ischemia/reperfusion (MI/R) injury in a DCD heart model after ex vivo perfusion. MAIN METHODS: Donor hearts were harvested from DCD model rats pre-treated with or without melatonin and subjected to 30 min of ex vivo perfusion, followed by transplantation. Tissue samples were obtained at 3, 12, and 24 h after heart transplantation. Myocardial oedema was evaluated based on the water content and wet/dry ratio, while inflammation was examined with hematoxylin & eosin staining. The expression levels of matrix metalloproteinase-9, interleukin-6, and tumour necrosis factor-α were evaluated. Oxidative stress level was determined from the content of malondialdehyde, activities of superoxide dismutase and glutathione peroxidase, and expression of Nrf2, NQO1 and cytochrome-C. Myocardial apoptosis was detected with TUNEL assay and measurement of the expression levels of Bax, Bcl-2, caspase-3, and cleaved caspase-3. The activation of the JAK2/STAT3 signalling pathway was evaluated by determining the levels of p-JAK2 and p-STAT3. KEY FINDINGS: Melatonin pre-treatment protected the heart from MI/R by reducing myocardial oedema and inflammation, attenuating oxidative stress, and decreasing myocardial apoptosis. Furthermore, the JAK2/STAT3 signalling pathway was activated after melatonin treatment during MI/R. The protective effects of melatonin were abolished by AG490. SIGNIFICANCE: Melatonin pre-treatment protected the heart from MI/R in a DCD heart model after ex vivo perfusion. Melatonin exerted cardioprotective effects through the activation of the JAK2/STAT3 signalling pathway.
AIMS: The shortage of donor hearts could be alleviated with the use of the allografts from donation after circulatory death (DCD). Here, we evaluated the protective effect of melatonin on myocardial ischemia/reperfusion (MI/R) injury in a DCD heart model after ex vivo perfusion. MAIN METHODS:Donor hearts were harvested from DCD model rats pre-treated with or without melatonin and subjected to 30 min of ex vivo perfusion, followed by transplantation. Tissue samples were obtained at 3, 12, and 24 h after heart transplantation. Myocardial oedema was evaluated based on the water content and wet/dry ratio, while inflammation was examined with hematoxylin & eosin staining. The expression levels of matrix metalloproteinase-9, interleukin-6, and tumour necrosis factor-α were evaluated. Oxidative stress level was determined from the content of malondialdehyde, activities of superoxide dismutase and glutathione peroxidase, and expression of Nrf2, NQO1 and cytochrome-C. Myocardial apoptosis was detected with TUNEL assay and measurement of the expression levels of Bax, Bcl-2, caspase-3, and cleaved caspase-3. The activation of the JAK2/STAT3 signalling pathway was evaluated by determining the levels of p-JAK2 and p-STAT3. KEY FINDINGS:Melatonin pre-treatment protected the heart from MI/R by reducing myocardial oedema and inflammation, attenuating oxidative stress, and decreasing myocardial apoptosis. Furthermore, the JAK2/STAT3 signalling pathway was activated after melatonin treatment during MI/R. The protective effects of melatonin were abolished by AG490. SIGNIFICANCE: Melatonin pre-treatment protected the heart from MI/R in a DCD heart model after ex vivo perfusion. Melatonin exerted cardioprotective effects through the activation of the JAK2/STAT3 signalling pathway.
Authors: Nora Palomo-López; Ana Rodríguez-Rodríguez; Luis Martín-Villén; María Mendoza-Prieto; Zaida Ruiz de Azúa-López; Lluis Sempere-Bordes; Laura Boyero-Corral; Domingo Daga-Ruiz; Antonio Gordillo-Brenes; María Pacheco-Sánchez; José Miguel Perez-Villares; Ángel Vilches-Arenas; Juan José Egea-Guerrero Journal: Healthcare (Basel) Date: 2022-04-20