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Sci Rep. 2017 Sep 27;7(1):12343. doi: 10.1038/s41598-017-11985-5.

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

Author information

1
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
2
The Zena and Michael A. Wiener CVI, Icahn School of Medicine at Mount Sinai, New York, USA.
3
CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
4
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. bibanez@cnic.es.
5
CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. bibanez@cnic.es.
6
IIS-Fundación Jiménez Díaz Hospital, Madrid, Spain. bibanez@cnic.es.
7
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. jvazquez@cnic.es.
8
CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. jvazquez@cnic.es.

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.

PMID:
28955040
PMCID:
PMC5617837
DOI:
10.1038/s41598-017-11985-5
[Indexed for MEDLINE]
Free PMC Article

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