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09 27, 2017;7 (1): 12343.

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
Author Information
  1. Aleksandra Binek: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. ORCID
  2. Rodrigo Fernández-Jiménez: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
  3. Inmaculada Jorge: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
  4. Emilio Camafeita: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. ORCID
  5. Juan Antonio López: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
  6. Navratan Bagwan: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
  7. Carlos Galán-Arriola: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
  8. Andres Pun: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
  9. Jaume Agüero: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
  10. Valentin Fuster: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
  11. Borja Ibanez: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. bibanez@cnic.es.
  12. Jesús Vázquez: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. jvazquez@cnic.es. ORCID
PMID: 28955040 DOI: 10.1038/s41598-017-11985-5

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.

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MeSH Term

Animals
Disease Models, Animal
Edema, Cardiac
Humans
Longitudinal Studies
Male
Myocardial Contraction
Myocardial Infarction
Myocardial Reperfusion Injury
Myocardium
Proteomics
Sus scrofa
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

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