Midkine is elevated after multiple trauma and acts directly on human cardiomyocytes by altering their functionality and metabolism
Wissenschaftlicher Artikel
Authors
Lackner, Ina
Weber, Birte
Baur, Meike
Haffner-Luntzer, Melanie
Eiseler, Tim
Faculties
Medizinische FakultätInstitutions
UKU. Klinik für Unfall-, Hand-, Plastische- und WiederherstellungschirurgieUKU. Institut für Unfallchirurgische Forschung und Biomechanik
UKU. Klinik für Innere Medizin I
Institut für Allgemeine Physiologie
External cooperations
Goethe Universität Frankfurt am MainUniversitätsspital Zürich
Published in
Frontiers in Immunology ; 10 (2019). - Art.-Nr. 1920. - eISSN 1664-3224
Link to original publication
https://dx.doi.org/10.3389/fimmu.2019.01920Peer review
ja
Document version
publishedVersion
Abstract
Background and Purpose: Post-traumatic cardiac dysfunction often occurs in
multiply injured patients (ISS ≥ 16). Next to direct cardiac injury, post-traumatic cardiac
dysfunction is mostly induced by the release of inflammatory biomarkers. One of these is
the heparin-binding factor Midkine, which is elevated in humans after fracture, burn injury
and traumatic spinal cord injury. Midkine is associated with cardiac pathologies but the
exact role of Midkine in the development of those diseases is ambiguous. The systemic
profile of Midkine after multiple trauma, its effects on cardiomyocytes and the association
with post-traumatic cardiac dysfunction, remain unknown.
Experimental Approach: Midkine levels were investigated in blood plasma of multiply
injured humans and pigs. Furthermore, human cardiomyocytes (iPS) were cultured
in presence/absence of Midkine and analyzed regarding viability, apoptosis, calcium
handling,metabolic alterations, and oxidative stress. Finally, theMidkine filtration capacity
of the therapeutic blood absorption column CytoSorb ®300 was tested with recombinant
Midkine or plasma from multiply injured patients.
Key Results: Midkine levels were significantly increased in blood plasma of multiply
injured humans and pigs. Midkine acts on human cardiomyocytes, altering their
mitochondrial respiration and calcium handling in vitro. CytoSorb®300 filtration reduced
Midkine concentration ex vivo and in vitro depending on the dosage.
Conclusion and Implications: Midkine is elevated in human and porcine plasma after
multiple trauma, affecting the functionality and metabolism of human cardiomyocytes
in vitro. Further examinations are required to determine whether the application of
CytoSorb®300 filtration in patients after multiple trauma is a promising therapeutic
approach to prevent post-traumatic cardiac disfunction.
Funding information
SFB 1149: Gefahrenantwort, Störfaktoren und regeneratives Potential nach akutem Trauma / DFG [251293561]
Effects of standard reaming and RIA techniques on local soft tissue and systemic homeostasis in a porcine trauma model /EU [S-16-133T]
Effects of standard reaming and RIA techniques on local soft tissue and systemic homeostasis in a porcine trauma model /EU [S-16-133T]
Subject Headings
Polytrauma [GND]Knochenbruch [GND]
Multiple trauma [MeSH]
Arrhythmias, Cardiac [MeSH]
Fractures, Bone; Therapy [MeSH]
Toll-like receptors [MeSH]
Keywords
CytoSorb® 300; Fracture treatment; Toll-like receptor signaling; Damage associated molecular pattern; Prevention cardiac injuryDewey Decimal Group
DDC 610 / Medicine & healthMetadata
Show full item recordCitation example
Lackner, Ina et al. (2021): Midkine is elevated after multiple trauma and acts directly on human cardiomyocytes by altering their functionality and metabolism. Open Access Repositorium der Universität Ulm. http://dx.doi.org/10.18725/OPARU-35441