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American Heart Association

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Final ID: Wed042

Unveiling the Cardioprotective Role of Sialidase Neu3 in Cardiac Ischemia and Reperfusion Injury

Abstract Body: Coronary reperfusion restores blood flow after acute myocardial infarction, but also triggers ischemia-reperfusion injury (IRI), which exacerbates tissue damage and promotes heart failure. Despite the urgent need for cardioprotective strategies, none have been successfully translated into clinical practice, highlighting the importance of deeply understanding the pathophysiology of IRI. In this context, our group has previously demonstrated that the sialidase Neu3, which removes sialic acid from glycosphingolipids, is modulated during IRI in vivo and that its overexpression in rat cardiomyoblasts protects against IRI via the reperfusion injury salvage kinase (RISK) and HIF-1α pathways activation. Therefore, this study aims to further elucidate the cardioprotective role of Neu3 by developing an inducible, cardiac-specific mouse model for Neu3 overexpression.
Inducible cardiac-specific Neu3-overexpressing mice (αMHC-Cre/LSL-Neu3) were generated by crossing a tamoxifen-inducible α-MHC-Cre mouse with a transgenic mouse carrying a floxed transcriptional STOP sequence upstream of the Neu3 gene.
Tamoxifen-treated αMHC-Cre/LSL-Neu3 mice showed significant Neu3 overexpression with reduced sialic acid levels in cardiomyocytes measured with specific lectins. No appreciable differences in cardiac morphology or functionality were observed between these mice and their wild-type counterparts. However, after surgical induction of IRI, the αMHC-Cre/LSL-Neu3 mice showed a significant reduction in infarct size as determined by Evans blue/TTC double staining, accompanied by improved cardiac functionality.
Possible molecular mechanisms underlying the observed effects were investigated by proteomic analysis of the damaged cardiac tissue. The analyses indicate that Neu3 attenuates inflammatory responses, preserves the mechanical and contractile properties of the heart and improves the structural integrity of cardiac tissue.
These results suggest that sialidase Neu3 is a promising target to promote cardioprotection and reduce the severity of myocardial infarction.
  • Cirillo, Federica  ( IRCCS Policlinico San Donato , San Donato Milanese , Italy )
  • Anastasia, Luigi  ( Vita-Salute San Raffaele University , MIlan , Italy )
  • Piccoli, Marco  ( IRCCS Policlinico San Donato , San Donato Milanese , Italy )
  • Lavota, Ivana  ( IRCCS Policlinico San Donato , San Donato Milanese , Italy )
  • Dallavilla, Tiziano  ( IRCCS Policlinico San Donato , San Donato Milanese , Italy )
  • Giavaldi, Aurora  ( IRCCS Policlinico San Donato , San Donato Milanese , Italy )
  • Mornatti, Lorenzo  ( IRCCS Policlinico San Donato , San Donato Milanese , Italy )
  • Fontana, Elisabetta  ( IRCCS Policlinico San Donato , San Donato Milanese , Italy )
  • Rota, Paola  ( University of Milan , Milan , Italy )
  • Villa, Marco  ( IRCCS Policlinico San Donato , San Donato Milanese , Italy )
  • Pappone, Carlo  ( IRCCS Policlinico San Donato , San Donato Milanese , Italy )
  • Author Disclosures:
    Federica Cirillo: DO NOT have relevant financial relationships | Luigi Anastasia: DO NOT have relevant financial relationships | Marco Piccoli: DO NOT have relevant financial relationships | Ivana Lavota: No Answer | Tiziano Dallavilla: No Answer | Aurora Giavaldi: No Answer | Lorenzo Mornatti: No Answer | Elisabetta Fontana: No Answer | Paola Rota: No Answer | Marco Villa: No Answer | Carlo Pappone: No Answer
Meeting Info:

Basic Cardiovascular Sciences 2025

2025

Baltimore, Maryland

Session Info:

Poster Session and Reception 1

Wednesday, 07/23/2025 , 04:30PM - 07:00PM

Poster Session and Reception

More abstracts from these authors:
Counteracting Cardiac Ischemia and Reperfusion Injury: the role of Sialidase Neu3

Piccoli Marco, Coviello Simona, Borella Rossana, Lavota Ivana, Cirillo Federica, Ghiroldi Andrea, Pappone Carlo, Anastasia Luigi

Restoring NaV1.5 Mutant Functionality in Arrhythmia with ManNAc Supplementation

Tarantino Adriana, Melgari Dario, Lavota Ivana, Rota Paola, Frosio Anthony, Rivolta Ilaria, Pappone Carlo, Anastasia Luigi

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