Chinese Journal of Tissue Engineering Research ›› 2023, Vol. 27 ›› Issue (28): 4519-4524.doi: 10.12307/2023.568

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Relaxin protects myocardial microvascular endothelial cells from hypoxia-reoxygenation injury

Wei Qin1, 2, Amanguli·Ruze2, 3, Chen Bingxin4, Zhao Ling2, 3, Zhao Banghao2, 3, Jiang Tao2, 5, Zhang Chun2, 5, Li Zhiqiang2, 5, Gao Xiaoming2, 3, 6, Duan Mingjun2, 5   

  1. 1Center Laboratory, 5Animal Laboratory Center, 6Institute of Clinical Medicine, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China; 2Xinjiang Key Laboratory of Medical Animal Model Research, Urumqi 830054, Xinjiang Uygur Autonomous Region, China; 3Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi 830054, Xinjiang Uygur Autonomous Region, China; 4Department of Cardiac Function, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
  • Received:2022-08-16 Accepted:2022-09-24 Online:2023-10-08 Published:2023-01-29
  • Contact: Gao Xiaoming, MD, Professor, Researcher, Xinjiang Key Laboratory of Medical Animal Model Research, Urumqi 830054, Xinjiang Uygur Autonomous Region, China; Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi 830054, Xinjiang Uygur Autonomous Region, China; Institute of Clinical Medicine, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China Duan Mingjun, Master, Assistant researcher, Xinjiang Key Laboratory of Medical Animal Model Research, Urumqi 830054, Xinjiang Uygur Autonomous Region, China; Animal Laboratory Center, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
  • About author:Wei Qin, Master, Experimentalist, Center Laboratory, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China; Xinjiang Key Laboratory of Medical Animal Model Research, Urumqi 830054, Xinjiang Uygur Autonomous Region, China Amanguli·Ruze, MD, Assistant researcher, Xinjiang Key Laboratory of Medical Animal Model Research, Urumqi 830054, Xinjiang Uygur Autonomous Region, China; Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
  • Supported by:
    the Open Projects of Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Nos. SKL-HIDCA-2017-Y11 (to DMJ) and SKL-HIDCA-2021-XXG1 (to ARZ); Natural Science Foundation of Xinjiang Uygur Autonomous Region, No. 2018D01C197 (to DMJ); the Open Project of the Key Laboratory of Xinjiang Uygur Autonomous Region, No 2021D04020 (to GXM)

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Abstract: BACKGROUND: Relaxin can significantly improve cardiac and renal dysfuction caused by pathological factors, inhibit myocardial hypertrophy, have an anti-fibrosis effect, and improve ischemia-reperfusion injury. However, its protective mechanism against hypoxia-reoxygenation injury of endothelial cells remains unclear.
OBJECTIVE: To investigate the protective mechanism of relaxin against hypoxia-reoxygenation injury of myocardial microvascular endothelial cells.
METHODS: Mouse myocardial microvascular endothelial cell line (H5V cells) was used for the experiment. Cells were treated by three different interventions: in control group, cells were normally cultured for 33 hours; in model group, cells were treated by 6-hour hypoxia followed by 3-hour reoxygenation); and in relaxin group, 24 hours of routine culture (180 ng/mL relaxin), 6 hours of hypoxia and 3 hours of reoxygenation (180 ng/mL relaxin) were given to simulate myocardial hypoxia-reperfusion injury. Cell permeability and Caspase-3 activity were then detected. Levels of tumor necrosis factor-α, interleukin-1β and interleukin-6 in cell supernatants were detected by ELISA. Expressions of VE-cadherin, Akt, and GSK-3β at mRNA and protein levels were detected by RT-PCR and western blot, respectively.
RESULTS AND CONCLUSION: Compared with the control group, the cell permeability and expression of caspase-3 increased significantly in the model group (P < 0.05). Compared with the model group, the cell permeability and expression of caspase-3 decreased in the relaxin group (P < 0.05). Moreover, the levels of tumor necrosis factor-α, interleukin-1β and interleukin-6 were elevated in the model group, while the levels were significantly decreased after relaxin treatment (all P < 0.05). There were no significantly changes in the mRNA and protein expressions of VE-cadherin, Akt1, and GSK-3β mRNA among three groups (all P > 0.05). Compared with the control group, the expression of phosphorylated VE-cadherin, Akt1 and GSK-3β were decreased in the model group (P < 0.05), and relaxin treatment reversed these changes to the control levels (P < 0.05). To conclude, relaxin treatment could enhance VE-cadherin expression, reduce hypoxia-reoxygenation-induced microvascular endothelial cell damage, inhibit inflammatory cytokine release, and reduce cell apoptosis, which may be related to the activation of the Akt/GSK-3β signaling pathway.

Key words: relaxin, cardiovascular disease, Akt/GSK-3β, endothelial cell permeability, apoptosis, inflammatory cytokine

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