Mitsugumin 53 Protects Against Warm Ischemia-Reperfusion Injury in a Murine Heart Transplantation Model
Presented During:
Monday, May 4, 2026: 9:00AM - 4:00PM
McCormick Place Lakeside Center
Posted Room Name:
Exhibit Hall, Poster Area
Abstract No:
P0140
Submission Type:
C. Walton Lillehei Resident Forum
Authors:
Tony Boualoy (1), Dhiaeddine Djabri (2), Martin Walsh (3), Zhentao Zhang (4), Xi Wang (4), Yong Gyu Lee (5), Jung Lye Kim (5), Doug Gouchoe (2), Sylvester Black (6), Hua Zhu (4), Bryan Whitson (7)
Institutions:
(1) The Ohio State Medical center and Nationwide Childrens Hospital, Pickerington, OH, (2) The Ohio State Medical center and Nationwide Childrens Hospital, Columbus, OH, (3) Ohio State Wexner Medical Center, Columbus, OH, (4) The Ohio State University Wexner Medical Center, Columbus, OH, (5) COPPER Lab (Collaboration for Organ Perfusion, Protection, Engineering, and Regeneration Laboratory), Columbus, OH, (6) 5Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, OH, (7) Ohio State University, Columbus, OH
Submitting Author:
Tony Boualoy
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The Ohio State Medical center and Nationwide Childrens Hospital
The Ohio State Medical center and Nationwide Childrens Hospital
Co-Author(s):
Dhiaeddine Djabri
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The Ohio State Medical center and Nationwide Childrens Hospital
The Ohio State Medical center and Nationwide Childrens Hospital
Martin Walsh
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Ohio State Wexner Medical Center
Ohio State Wexner Medical Center
Zhentao Zhang
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The Ohio State University Wexner Medical Center
The Ohio State University Wexner Medical Center
Xi Wang
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The Ohio State University Wexner Medical Center
The Ohio State University Wexner Medical Center
Yong Gyu Lee
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COPPER Lab (Collaboration for Organ Perfusion, Protection, Engineering, and Regeneration Laboratory)
COPPER Lab (Collaboration for Organ Perfusion, Protection, Engineering, and Regeneration Laboratory)
Jung Lye Kim
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COPPER Lab (Collaboration for Organ Perfusion, Protection, Engineering, and Regeneration Laboratory)
COPPER Lab (Collaboration for Organ Perfusion, Protection, Engineering, and Regeneration Laboratory)
Doug Gouchoe
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The Ohio State Medical center and Nationwide Childrens Hospital
The Ohio State Medical center and Nationwide Childrens Hospital
Sylvester Black
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5Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center
5Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center
Hua Zhu
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The Ohio State University Wexner Medical Center
The Ohio State University Wexner Medical Center
*Bryan Whitson
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Ohio State University
Ohio State University
Presenting Author:
Tony Boualoy
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The Ohio State Medical center and Nationwide Childrens Hospital
The Ohio State Medical center and Nationwide Childrens Hospital
Abstract:
Objective: Ischemia-reperfusion injury (IRI) during heart transplantation contributes to early graft dysfunction through cellular injury and inflammation. Mitsugumin 53 (MG53) is an endogenous membrane-repair protein that modulates the inflammasome activation. We hypothesized that IRI would be amplified in the absence of circulating MG53 and mitigated by increased MG53 expression.
Methods: Wild-type (WT) donor hearts were heterotopically transplanted into WT, MG53-knockout (MG53KO), and transgenic plasma-overexpressed MG53 (tPA) recipient mice following 15 minutes of warm ischemia and 4 hours of cold storage at 4 °C. Mice were monitored for 24 hours (acute phase) and up to 14 days (resolution phase) post-transplantation. Beating scores were recorded daily as the primary functional endpoint. Plasma and graft tissues were analyzed for markers of inflammation and cellular injury, including IL-1β, IL-18, and lactate dehydrogenase (LDH).
Results: A total of 31 mice were included (15 sacrificed at 24 hours, 16 at 14 days). MG53KO recipients exhibited significantly higher plasma IL-1β concentrations compared with WT (p < 0.01) and tPA recipients (p < 0.001). By 14 days, IL-1β levels had declined and no longer differed among groups (Fig. 1a). At 24 hours, LDH levels were significantly elevated in MG53KO and WT recipients compared to WT donor no-transplant controls (p < 0.01), but not in tPA recipients. By 14 days, LDH levels decreased comparably in all cohorts. IL-18 levels did not differ significantly between groups at either time point. WT recipients demonstrated consistently higher beating scores throughout follow-up. By day 5, MG53KO graft beating scores declined significantly compared to WT (2.8 vs 4.0, p < 0.05), and by day 11, tPA grafts declined compared with WT (2.5 vs 3.8, p < 0.05) (Fig. 1b).
Conclusions: In this murine heart transplantation model of allograft warm ischemic injury, the absence of MG53 led to heightened inflammatory response and reduced graft function. Overexpression of MG53 conferred early protection during the acute phase of IRI, attenuating cellular inflammation and preserving graft activity. These findings suggest that MG53 is a promising therapeutic target for mitigating IRI in heart transplantation.
Methods: Wild-type (WT) donor hearts were heterotopically transplanted into WT, MG53-knockout (MG53KO), and transgenic plasma-overexpressed MG53 (tPA) recipient mice following 15 minutes of warm ischemia and 4 hours of cold storage at 4 °C. Mice were monitored for 24 hours (acute phase) and up to 14 days (resolution phase) post-transplantation. Beating scores were recorded daily as the primary functional endpoint. Plasma and graft tissues were analyzed for markers of inflammation and cellular injury, including IL-1β, IL-18, and lactate dehydrogenase (LDH).
Results: A total of 31 mice were included (15 sacrificed at 24 hours, 16 at 14 days). MG53KO recipients exhibited significantly higher plasma IL-1β concentrations compared with WT (p < 0.01) and tPA recipients (p < 0.001). By 14 days, IL-1β levels had declined and no longer differed among groups (Fig. 1a). At 24 hours, LDH levels were significantly elevated in MG53KO and WT recipients compared to WT donor no-transplant controls (p < 0.01), but not in tPA recipients. By 14 days, LDH levels decreased comparably in all cohorts. IL-18 levels did not differ significantly between groups at either time point. WT recipients demonstrated consistently higher beating scores throughout follow-up. By day 5, MG53KO graft beating scores declined significantly compared to WT (2.8 vs 4.0, p < 0.05), and by day 11, tPA grafts declined compared with WT (2.5 vs 3.8, p < 0.05) (Fig. 1b).
Conclusions: In this murine heart transplantation model of allograft warm ischemic injury, the absence of MG53 led to heightened inflammatory response and reduced graft function. Overexpression of MG53 conferred early protection during the acute phase of IRI, attenuating cellular inflammation and preserving graft activity. These findings suggest that MG53 is a promising therapeutic target for mitigating IRI in heart transplantation.
Category:
Adult Cardiac
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