TY - JOUR
T1 - Protein Alterations in Cardiac Ischemia/Reperfusion Revealed by Spatial-Omics
AU - Mezger, Stephanie T P
AU - Mingels, Alma M A
AU - Soulié, Matthieu
AU - Peutz-Kootstra, Carine J
AU - Bekers, Otto
AU - Mulder, Paul
AU - Heeren, Ron M A
AU - Cillero-Pastor, Berta
N1 - Funding Information:
RMAH: BCP and STPM were partly funded by the LINK program of the Dutch Province of Limburg. STPM, RMAH, AMAM and OB received funding from the Maastricht University Medical Center. AMAM received funding from the Dutch government, ZonMW/NWO (09150161810155).
Publisher Copyright:
© 2022 by the authors.
PY - 2022/11/10
Y1 - 2022/11/10
N2 - Myocardial infarction is the most common cause of death worldwide. An understanding of the alterations in protein pathways is needed in order to develop strategies that minimize myocardial damage. To identify the protein signature of cardiac ischemia/reperfusion (I/R) injury in rats, we combined, for the first time, protein matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and label-free proteomics on the same tissue section placed on a conductive slide. Wistar rats were subjected to I/R surgery and sacrificed after 24 h. Protein MALDI-MSI data revealed ischemia specific regions, and distinct profiles for the infarct core and border. Firstly, the infarct core, compared to histologically unaffected tissue, showed a significant downregulation of cardiac biomarkers, while an upregulation was seen for coagulation and immune response proteins. Interestingly, within the infarct tissue, alterations in the cytoskeleton reorganization and inflammation were found. This work demonstrates that a single tissue section can be used for protein-based spatial-omics, combining MALDI-MSI and label-free proteomics. Our workflow offers a new methodology to investigate the mechanisms of cardiac I/R injury at the protein level for new strategies to minimize damage after MI.
AB - Myocardial infarction is the most common cause of death worldwide. An understanding of the alterations in protein pathways is needed in order to develop strategies that minimize myocardial damage. To identify the protein signature of cardiac ischemia/reperfusion (I/R) injury in rats, we combined, for the first time, protein matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and label-free proteomics on the same tissue section placed on a conductive slide. Wistar rats were subjected to I/R surgery and sacrificed after 24 h. Protein MALDI-MSI data revealed ischemia specific regions, and distinct profiles for the infarct core and border. Firstly, the infarct core, compared to histologically unaffected tissue, showed a significant downregulation of cardiac biomarkers, while an upregulation was seen for coagulation and immune response proteins. Interestingly, within the infarct tissue, alterations in the cytoskeleton reorganization and inflammation were found. This work demonstrates that a single tissue section can be used for protein-based spatial-omics, combining MALDI-MSI and label-free proteomics. Our workflow offers a new methodology to investigate the mechanisms of cardiac I/R injury at the protein level for new strategies to minimize damage after MI.
KW - Animals
KW - Rats
KW - Rats, Wistar
KW - Coronary Artery Disease
KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
KW - Myocardial Infarction/pathology
KW - Reperfusion Injury
KW - Reperfusion
U2 - 10.3390/ijms232213847
DO - 10.3390/ijms232213847
M3 - Article
C2 - 36430335
SN - 1661-6596
VL - 23
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 22
M1 - 13847
ER -