Proteomic footprint of myocardial ischemia/reperfusion injury: Longitudinal study of the at-risk and remote regions in the pig model

Aleksandra Binek, Rodrigo Fernández-Jiménez, Inmaculada Jorge, Emilio Camafeita, Juan Antonio López, Navratan Bagwan, Carlos Galán-Arriola, Andres Pun, Jaume Agüero, Valentin Fuster, Borja Ibanez, Jesús Vázquez

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Reperfusion alters post-myocardial infarction (MI) healing; however, very few systematic studies report the early molecular changes following ischemia/reperfusion (I/R). Alterations in the remote myocardium have also been neglected, disregarding its contribution to post-MI heart failure (HF) development. This study characterizes protein dynamics and contractile abnormalities in the ischemic and remote myocardium during one week after MI. Closed-chest 40 min I/R was performed in 20 pigs sacrificed at 120 min, 24 hours, 4days, and 7days after reperfusion (n = 5 per group). Myocardial contractility was followed up by cardiac magnetic resonance (CMR) and tissue samples were analyzed by multiplexed quantitative proteomics. At early reperfusion (120 min), the ischemic area showed a coordinated upregulation of inflammatory processes, whereas interstitial proteins, angiogenesis and cardio-renal signaling processes increased at later reperfusion (day 4 and 7). Remote myocardium showed decreased contractility at 120 min- and 24 h-CMR accompanied by transient alterations in contractile and mitochondrial proteins. Subsequent recovery of regional contractility was associated with edema formation on CMR and increases in inflammation and wound healing proteins on post-MI day 7. Our results establish for the first time the altered protein signatures in the ischemic and remote myocardium early after I/R and might have implications for new therapeutic targets to improve early post-MI remodeling.

Original languageEnglish
Article number12343
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - 1 Dec 2017

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