Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation
BackgroundThe utilization of donation after circulatory death (DCD) hearts can enlarge the donor pool. However, DCD hearts suffer from serious ischemia/reperfusion injury (IRI). Recent studies found that the activation of NLRP3 inflammasome could play a significant role in organ IRI. Mcc950, which i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1126391/full |
| _version_ | 1797868255381028864 |
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| author | Liwei Xu Zifeng Zeng Chuanjie Niu Deshen Liu Shaoyan Lin Xiu Liu Gábor Szabó Gábor Szabó Jun Lu Shaoyi Zheng Pengyu Zhou |
| author_facet | Liwei Xu Zifeng Zeng Chuanjie Niu Deshen Liu Shaoyan Lin Xiu Liu Gábor Szabó Gábor Szabó Jun Lu Shaoyi Zheng Pengyu Zhou |
| author_sort | Liwei Xu |
| collection | DOAJ |
| description | BackgroundThe utilization of donation after circulatory death (DCD) hearts can enlarge the donor pool. However, DCD hearts suffer from serious ischemia/reperfusion injury (IRI). Recent studies found that the activation of NLRP3 inflammasome could play a significant role in organ IRI. Mcc950, which is a novel inhibitor of the NLRP3 inflammasome, can be applied to treat various kinds of cardiovascular diseases. Therefore, we hypothesized that the treatment of mcc950 could protect DCD hearts preserved with normothermic ex vivo heart perfusion (EVHP) against myocardial IRI via inhibiting NLRP3 inflammasome in a rat heart transplantation model of DCD.MethodsDonor-heart rats were randomly divided into four groups: Control group; Vehicle group; MP-mcc950 group; and MP + PO-mcc950 group. Mcc950 was added into the perfusate of normothermic EVHP in the MP-mcc950 and MP + PO-mcc950 groups, and was injected into the left external jugular vein after heart transplantation in the MP + PO-mcc950 group. Cardiac functional assessment was performed. The level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-associated protein of donor hearts were evaluated.ResultsThe treatment with mcc950 significantly increased the developed pressure (DP), dP/dtmax, and dP/dtmin of the left ventricular of DCD hearts at 90 min after heart transplantation in both MP-mcc950 and MP + PO-mcc950 groups. Furthermore, mcc950 added into perfusate and injected after transplantation in both MP-mcc950 and MP + PO-mcc950 groups significantly attenuated the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome compared with the vehicle group.ConclusionsNormothermic EVHP combined with mcc950 treatment can be a promising and novel DCD heart preservation strategy, which can alleviate myocardial IRI via inhibiting NLRP3 inflammasome. |
| first_indexed | 2024-04-09T23:54:09Z |
| format | Article |
| id | doaj.art-f8017dd361894a47a36b9df668912299 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-09T23:54:09Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-f8017dd361894a47a36b9df6689122992023-03-17T04:51:22ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-03-011010.3389/fcvm.2023.11263911126391Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantationLiwei Xu0Zifeng Zeng1Chuanjie Niu2Deshen Liu3Shaoyan Lin4Xiu Liu5Gábor Szabó6Gábor Szabó7Jun Lu8Shaoyi Zheng9Pengyu Zhou10Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cardiac Surgery, University of Heidelberg, Heidelberg, GermanyDepartment of Cardiac Surgery, University of Halle (Saale), Halle, GermanyDepartment of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaBackgroundThe utilization of donation after circulatory death (DCD) hearts can enlarge the donor pool. However, DCD hearts suffer from serious ischemia/reperfusion injury (IRI). Recent studies found that the activation of NLRP3 inflammasome could play a significant role in organ IRI. Mcc950, which is a novel inhibitor of the NLRP3 inflammasome, can be applied to treat various kinds of cardiovascular diseases. Therefore, we hypothesized that the treatment of mcc950 could protect DCD hearts preserved with normothermic ex vivo heart perfusion (EVHP) against myocardial IRI via inhibiting NLRP3 inflammasome in a rat heart transplantation model of DCD.MethodsDonor-heart rats were randomly divided into four groups: Control group; Vehicle group; MP-mcc950 group; and MP + PO-mcc950 group. Mcc950 was added into the perfusate of normothermic EVHP in the MP-mcc950 and MP + PO-mcc950 groups, and was injected into the left external jugular vein after heart transplantation in the MP + PO-mcc950 group. Cardiac functional assessment was performed. The level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-associated protein of donor hearts were evaluated.ResultsThe treatment with mcc950 significantly increased the developed pressure (DP), dP/dtmax, and dP/dtmin of the left ventricular of DCD hearts at 90 min after heart transplantation in both MP-mcc950 and MP + PO-mcc950 groups. Furthermore, mcc950 added into perfusate and injected after transplantation in both MP-mcc950 and MP + PO-mcc950 groups significantly attenuated the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome compared with the vehicle group.ConclusionsNormothermic EVHP combined with mcc950 treatment can be a promising and novel DCD heart preservation strategy, which can alleviate myocardial IRI via inhibiting NLRP3 inflammasome.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1126391/fullheart transplantationcardiovascular diseasesNLRP3MCC950donation after circulatory deathmyocardial ischemia/reperfusion injury |
| spellingShingle | Liwei Xu Zifeng Zeng Chuanjie Niu Deshen Liu Shaoyan Lin Xiu Liu Gábor Szabó Gábor Szabó Jun Lu Shaoyi Zheng Pengyu Zhou Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation Frontiers in Cardiovascular Medicine heart transplantation cardiovascular diseases NLRP3 MCC950 donation after circulatory death myocardial ischemia/reperfusion injury |
| title | Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation |
| title_full | Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation |
| title_fullStr | Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation |
| title_full_unstemmed | Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation |
| title_short | Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation |
| title_sort | normothermic ex vivo heart perfusion with nlrp3 inflammasome inhibitor mcc950 treatment improves cardiac function of circulatory death hearts after transplantation |
| topic | heart transplantation cardiovascular diseases NLRP3 MCC950 donation after circulatory death myocardial ischemia/reperfusion injury |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1126391/full |
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