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Treatment with the CC chemokine-binding protein Evasin-4 improves post-infarction myocardial injury and survival in mice

Proudfoot, Amanda E
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Published in Thrombosis and haemostasis. 2013, vol. 110, no. 4, p. 807-25
Abstract Chemokines trigger leukocyte trafficking and are implicated in cardiovascular disease pathophysiology. Chemokine-binding proteins, called "Evasins" have been shown to inhibit both CC and CXC chemokine-mediated bioactivities. Here, we investigated whether treatment with Evasin-3 (CXC chemokine inhibitor) and Evasin-4 (CC chemokine inhibitor) could influence post-infarction myocardial injury and remodelling. C57Bl/6 mice were submitted in vivo to left coronary artery permanent ligature and followed up for different times (up to 21 days). After coronary occlusion, three intraperitoneal injections of 10 μg Evasin-3, 1 μg Evasin-4 or equal volume of vehicle (PBS) were performed at 5 minutes, 24 hours (h) and 48 h after ischaemia onset. Both anti-chemokine treatments were associated with the beneficial reduction in infarct size as compared to controls. This effect was accompanied by a decrease in post-infarction myocardial leukocyte infiltration, reactive oxygen species release, and circulating levels of CXCL1 and CCL2. Treatment with Evasin-4 induced a more potent effect, abrogating the inflammation already at one day after ischaemia onset. At days 1 and 21 after ischaemia onset, both anti-chemokine treatments failed to significantly improve cardiac function, remodelling and scar formation. At 21-day follow-up, mouse survival was exclusively improved by Evasin-4 treatment when compared to control vehicle. In conclusion, we showed that the selective inhibition of CC chemokines (i.e. CCL5) with Evasin-4 reduced cardiac injury/inflammation and improved survival. Despite the inhibition of CXC chemokine bioactivities, Evasin-3 did not affect mouse survival. Therefore, early inhibition of CC chemokines might represent a promising therapeutic approach to reduce the development of post-infarction heart failure in mice.
Keywords AnimalsAnti-Inflammatory Agents/administration & dosageCell Movement/drug effectsChemokine CXCL1/bloodCoronary Vessels/surgeryDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLMyocardial Infarction/diagnosis/drug therapyMyocardium/metabolism/pathologyOxidative Stress/drug effectsReceptors, CXCR/administration & dosageReceptors, Chemokine/administration & dosage
PMID: 23925450
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Article (Published version) (16.3 MB) - document accessible for UNIGE members only Limited access to UNIGE
Research groups Chimie et protéomique clinique (270)
Imagerie cardiaque fonctionnelle (541)
L'athérosclérose et ses complications cliniques (591)
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BRAUNERSREUTHER, Vincent et al. Treatment with the CC chemokine-binding protein Evasin-4 improves post-infarction myocardial injury and survival in mice. In: Thrombosis and haemostasis, 2013, vol. 110, n° 4, p. 807-25. doi: 10.1160/TH13-04-0297 https://archive-ouverte.unige.ch/unige:42927

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Deposited on : 2014-12-09

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