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Subacute treatment of carprofen facilitate splenocardiac resolution deficit in cardiac injury.

Abstract：

:Inflammation-limiting nonsteroidal pain relievers magnify myocardial infarction (MI) incidences and increase re-admission events in heart failure (HF) patients. However, the molecular and cellular mechanism of this provocative adverse effect is unclear. Our goal was to determine whether carprofen (CAP) impedes splenic leukocyte-directed acute inflammation-resolving response in cardiac injury. After subacute CAP treatment, mice were subjected to permanent coronary ligation maintaining MI- and naïve-controls. Spleen and left ventricle (LV) leukocytes were quantitated using flow cytometry pre- and 24 h post-MI. The inflammation resolution mediators were quantified using mass spectrometry while splenocardiac apoptosis and leukocyte phagocytosis were measured by immunofluorescence and ImageStream, respectively. Subacute CAP treatment promoted strain and cardiac dysfunction before MI and coronary occlusion showed signs of acute HF in CAP and MI-controls. Subacute CAP-injected mice had pre-activated splenic neutrophils, an over activated "don't eat me" signal (CD47) with reduced total Mϕs (F4/80+ ) and reparative Mϕs (F4/80/Ly6Clo /CD206) compared with control in LV and spleen. Post-MI, CAP pre-activated neutrophils (Ly6G+ ) were intensified and reduced reparative neutrophils (Ly6G+ /CD206+ ) and Mϕs (F4/80/Ly6Clo ) in LV was indicative of non-resolving inflammation compared with MI-control. Subacute CAP treatment deferred neutrophil phagocytosis functions in the spleen and LV and was more evident post-MI compared with MI-control. CAP pre-activated splenic neutrophils that tailored the Mϕ phagocytosis thereby increased splenocardiac leukocyte death. CAP over amplified COX-1 and COX-2 compared with MI-control and failed to limit prostaglandins and thromboxane in post-MI setting. Further, CAP reduced cardiac-protective epoxyeicosatrienoic acids and over amplified pyrogenic inflammatory cytokines and reduced reparative cytokines, thereby non-resolving inflammation.

journal_name

J Leukoc Biol

journal_title

Journal of leukocyte biology

authors

Halade GV,Kain V,Wright GM,Jadapalli JK

doi

10.1002/JLB.3A0618-223R

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

1173-1186

issue

eissn

0741-5400

issn

1938-3673

journal_volume

104

pub_type

杂志文章

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Subacute treatment of carprofen facilitate splenocardiac resolution deficit in cardiac injury.