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Reproducing extracellular matrix adverse remodelling of non-ST myocardial infarction in a large animal model

Title: Reproducing extracellular matrix adverse remodelling of non-ST myocardial infarction in a large animal model
Authors: Contessotto P.; Spelat R.; Ferro F.; Vysockas V.; Krivickienė A.; Jin C.; Chantepie S.; Chinello C.; Pauza A. G.; Valente C.; Rackauskas M.; Casara A.; Zigmantaitė V.; Magni F.; Papy-Garcia D.; Karlsson N. G.; Ereminienė E.; Pandit A.; Da Costa M.
Contributors: Contessotto, P; Spelat, R; Ferro, F; Vysockas, V; Krivickienė, A; Jin, C; Chantepie, S; Chinello, C; Pauza, A; Valente, C; Rackauskas, M; Casara, A; Zigmantaitė, V; Magni, F; Papy-Garcia, D; Karlsson, N; Ereminienė, E; Pandit, A; Da Costa, M
Publisher Information: Springer Nature; GB
Publication Year: 2023
Collection: Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive)
Subject Terms: Animal; Coronary Vessel; Extracellular Matrix; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Risk Factor; Sheep; ST Elevation Myocardial Infarction; Settore BIOS-07/A - Biochimica
Description: The rising incidence of non-ST-segment elevation myocardial infarction (NSTEMI) and associated long-term high mortality constitutes an urgent clinical issue. Unfortunately, the study of possible interventions to treat this pathology lacks a reproducible pre-clinical model. Indeed, currently adopted small and large animal models of MI mimic only full-thickness, ST-segment-elevation (STEMI) infarcts, and hence cater only for an investigation into therapeutics and interventions directed at this subset of MI. Thus, we develop an ovine model of NSTEMI by ligating the myocardial muscle at precise intervals parallel to the left anterior descending coronary artery. Upon histological and functional investigation to validate the proposed model and comparison with STEMI full ligation model, RNA-seq and proteomics show the distinctive features of post-NSTEMI tissue remodelling. Transcriptome and proteome-derived pathway analyses at acute (7 days) and late (28 days) post-NSTEMI pinpoint specific alterations in cardiac post-ischaemic extracellular matrix. Together with the rise of well-known markers of inflammation and fibrosis, NSTEMI ischaemic regions show distinctive patterns of complex galactosylated and sialylated N-glycans in cellular membranes and extracellular matrix. Identifying such changes in molecular moieties accessible to infusible and intra-myocardial injectable drugs sheds light on developing targeted pharmacological solutions to contrast adverse fibrotic remodelling.
Document Type: article in journal/newspaper
File Description: ELETTRONICO
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/36813782; info:eu-repo/semantics/altIdentifier/wos/WOS:001026242700003; volume:14; issue:1 (December 2023); journal:NATURE COMMUNICATIONS; https://hdl.handle.net/10281/533301
DOI: 10.1038/s41467-023-36350-1
Availability: https://hdl.handle.net/10281/533301; https://doi.org/10.1038/s41467-023-36350-1
Rights: info:eu-repo/semantics/openAccess ; license:Creative Commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.384358BD
Database: BASE