Dataset Information

The time-of-day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment.

ABSTRACT: Myocardial infarction (MI) is the leading cause of death in Western countries. Epidemiological studies show acute MI to be more prevalent in the morning and to be associated with a poorer outcome in terms of mortality and recovery. The mechanisms behind this association are not fully understood. Here, we report that circadian oscillations of neutrophil recruitment to the heart determine infarct size, healing, and cardiac function after MI Preferential cardiac neutrophil recruitment during the active phase (Zeitgeber time, ZT13) was paralleled by enhanced myeloid progenitor production, increased circulating numbers of CXCR2(hi) neutrophils as well as upregulated cardiac adhesion molecule and chemokine expression. MI at ZT13 resulted in significantly higher cardiac neutrophil infiltration compared to ZT5, which was inhibited by CXCR2 antagonism or neutrophil-specific CXCR2 knockout. Limiting exaggerated neutrophilic inflammation at this time point significantly reduced the infarct size and improved cardiac function.

SUBMITTER: Schloss MJ

PROVIDER: S-EPMC4967945 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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The time-of-day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment.

Schloss Maximilian J MJ Horckmans Michael M Nitz Katrin K Duchene Johan J Drechsler Maik M Bidzhekov Kiril K Scheiermann Christoph C Weber Christian C Soehnlein Oliver O Steffens Sabine S

EMBO molecular medicine 20160801 8

Myocardial infarction (MI) is the leading cause of death in Western countries. Epidemiological studies show acute MI to be more prevalent in the morning and to be associated with a poorer outcome in terms of mortality and recovery. The mechanisms behind this association are not fully understood. Here, we report that circadian oscillations of neutrophil recruitment to the heart determine infarct size, healing, and cardiac function after MI Preferential cardiac neutrophil recruitment during the ac ...[more]

PMID: 27226028

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Project description:Acute myocardial infarction (AMI) induces a rapid and robust inflammatory response characterized by infiltration of different immune cell types to the infarcted heart. The recruitment of immune cells is a dynamic process and consists of sequential infiltration of neutrophils, proand anti-inflammatory monocytes, and lymphocytes to the injured myocardium. neutrophils are the first responders to ischemic injury and have the ability to amplify the initial inflammatory response by deploying key alarmins such as S100A8 and S100A9. These alarmins interact with Toll-Like-Receptor (TLR4) on naïve neutrophils, prime the NLRP3 inflammasome and facilitate their migration to the bone marrow (BM). The reverse-migrated neutrophils are preferentially retained within the BM sinusoids by certain adhesion receptors, a process that is essential for the activation of Gasdermin D- dependent membrane pore formation and secretion of IL-1β. Under steady-state conditions, mature neutrophils are present in major reservoirs across the body (spleen, liver, BM, lungs, and vasculature) and are recruited following changes in homeostasis. The unique feature of neutrophils in the vasculature is their distribution into two distinct groups, the marginated and the demarginated. Firmly adherent to the vasculature walls, the marginated pool of neutrophils represents ~ 51% of neutrophils in circulation and are believed to serve as early responders. The demargination process in neutrophils is attributed to loss of adhesion molecules, and rearrangement of actin cytoskeleton within the cells. Under certain stress and inflammatory conditions, adhesion of neutrophils is altered, and the marginated cells detach and mobilize into the bloodstream, expanding the percentage of demarginated cells in the blood. We reasoned that the marginated pool of neutrophils may be mobilized to meet the sudden and increased demand of the ischemic heart. Thus, deciphering the signaling pathways that stimulate the demargination of neutrophils and their recruitment to the ischemic heart may provide a viable approach to regulate neutrophil trafficking to the heart post-MI.

Dataset Information

The time-of-day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment.

Publications

The time-of-day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment.

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