| Title: |
Pharmacological inhibition of the triggering receptor expressed on myeloid cells-1 limits reperfusion injury in a porcine model of myocardial infarction |
| Authors: |
Lemarié, Jérémie; Boufenzer, Amir; Popovic, Batric; Tran, Nguyen; Groubatch, Frederique; Derive, Marc; Labroca, Pierre; Barraud, Damien; Gibot, Sébastien |
| Contributors: |
Service de Soins Intensifs CHRU Nancy; Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy); Défaillance Cardiovasculaire Aiguë et Chronique (DCAC); Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL); Service de Cardiologie CHRU Nancy; École de chirurgie, faculté de médecine de Nancy; INOTREM; Service d'Anesthésiologie et de Soins Intensifs CHRU Nancy |
| Source: |
EISSN: 2055-5822 ; ESC Heart Failure ; https://hal.univ-lorraine.fr/hal-01757879 ; ESC Heart Failure, 2015, 2 (2), pp.90- 99. ⟨10.1002/ehf2.12029⟩ |
| Publisher Information: |
CCSD; Wiley |
| Publication Year: |
2015 |
| Collection: |
Université de Lorraine: HAL |
| Subject Terms: |
Immune system; Inflammation; Myocardial infarction; Reperfusion; [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system; [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy |
| Description: |
International audience ; AIMS: Limitation of ischemia/reperfusion injury is a major therapeutic target after acute myocardial infarction (AMI). Toll-like receptors are implicated in the inflammatory response that occurs during reperfusion. The triggering receptor expressed on myeloid cells (TREM)-1 acts as an amplifier of the immune response triggered by toll-like receptor engagement. We hypothesized that administration of a TREM-1 inhibitory peptide (LR12) could limit reperfusion injury in a porcine model of AMI.METHODS AND RESULTS: AMI was induced in 15 adult minipigs by a closed-chest coronary artery occlusion-reperfusion technique. Animals were randomized to receive LR12 or vehicle before reperfusion (LR12 n = 7, vehicle n = 8), and were monitored during 18 h. AMI altered hemodynamics and cardiac function, as illustrated by a drop of mean arterial pressure, cardiac index, cardiac power index, ejection fraction, and real-time pressure-volume loop-derived parameters. TREM-1 inhibition by LR12 significantly improved these dysfunctions (P < 0.03) and limited infarct size, as assessed by lower creatine phosphokinase and troponin I concentrations (P < 0.005). Pulmonary, renal, and hepatic impairments occurred after AMI and were attenuated by LR12 administration as assessed by a better PaO2 to FiO2 ratio, a less positive fluid balance, and lower liver enzymes levels (P < 0.05).CONCLUSION: Inhibition of the TREM-1 pathway by a synthetic peptide limited myocardial reperfusion injury in a clinically relevant porcine model of AMI. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/28834656; PUBMED: 28834656 |
| DOI: |
10.1002/ehf2.12029 |
| Availability: |
https://hal.univ-lorraine.fr/hal-01757879; https://hal.univ-lorraine.fr/hal-01757879v1/document; https://hal.univ-lorraine.fr/hal-01757879v1/file/Lemari-_et_al-2015-ESC_Heart_Failure.pdf; https://doi.org/10.1002/ehf2.12029 |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.836AC775 |
| Database: |
BASE |