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:Myocardial infarction (MI) is one of the most common cardiac emergencies with high morbidity and is a leading cause of death worldwide. Since MI could develop into a life-threatening emergency and could also seriously affect the life quality of patients, continuous efforts have been made to create an effective strategy to prevent the occurrence of MI and reduce MI-related mortality. Numerous studies have confirmed that neutrophils play important roles in inflammation and innate immunity, which provide the first line of defense against microorganisms by producing inflammatory cytokines and chemokines, releasing reactive oxygen species, and degranulating components of neutrophil cytoplasmic granules to kill pathogens. Recently, researchers reported that neutrophils are closely related to the severity and prognosis of patients with MI, and neutrophil to lymphocyte ratio in post-MI patients had predictive value for major adverse cardiac events. Neutrophils have been increasingly recognized to exert important functions in MI. Especially, granule proteins released by neutrophil degranulation after neutrophil activation have been suggested to involve in the process of MI. This article reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Video abstract Neutrophils played a crucial role throughout the process of MI, and neutrophil degranulation was the crucial step for the regulative function of neutrophils. Both neutrophils infiltrating and neutrophil degranulation take part in the injury and repair process immediately after the onset of MI. Since different granule subsets (e g. MPO, NE, NGAL, MMP-8, MMP-9, cathelicidin, arginase and azurocidin) released from neutrophil degranulation show different effects through diverse mechanisms in MI. In this review, we reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Myeloperoxidase (MPO); Neutrophil elastase (NE); Neutrophil gelatinase-associated lipocalin (NGAL); Matrix metalloproteinase 8 (MMP-8); Matrix metalloproteinase 9 (MMP-9).

Project description:AimsSuboptimal perfusion leading to heart failure (HF) often occurs after ST-segment elevation myocardial infarction (STEMI), despite restoration of epicardial coronary flow in primary percutaneous coronary intervention (PPCI) era. We determined the clinical implications of angio-based coronary functional assessment in evaluation of suboptimal perfusion and further outcomes among STEMI patients after successful PPCI.Methods and resultsIn this study, STEMI patients in the Chinese STEMI PPCI registry trial (NCT04996901) who achieved post-PPCI thrombolysis in myocardial infarction grade 3 flow were retrospectively screened. Post-procedural quantitative flow ratio (QFR), angio-based microvascular resistance (AMR), and coronary flow velocity (CFV) of the infarct-related artery were calculated. QFR and AMR measure epicardial stenosis severity and microvascular resistance, respectively. QFR+ was defined as QFR < 0.90 while QFR- was QFR ≥ 0.90. AMR+ was defined as AMR ≥ 250 mmHg*s/m while AMR- was AMR < 250 mmHg*s/m. The primary outcome was 30-day new-onset HF. The Kaplan-Meier curves were used to establish the associations between QFR, AMR, CFV, and HF incidences. The relationship between CFV and combined QFR and AMR indices was further assessed. Independent predictors were determined using Cox regression analysis. The receiver-operating characteristic curve was used to assess discriminant ability to predict HF. A total of 942 patients (mean age was 57.8 ± 11.7 years and 84.6% were men) were enrolled. Among them, 129 patients had new-onset HF episodes. Patients in the QFR-/AMR- group had a low risk of HF compared with those in the QFR+/AMR+ group (10.5% vs. 27.3%, P = 0.027). A higher CFV ≥ 17.4 cm/s was associated with low HF incidences as compared with CFV < 17.4 cm/s (10.3% vs. 16.8%, P = 0.005), whereas isolated QFR or AMR did not reveal any marked differences in HF incidences (P = 0.150 and 0.079, respectively). The highest and lowest medians of CFV were observed in the QFR-/AMR- and QFR+/AMR+ groups, respectively. CFV correlated well with the QFR/AMR ratio (adjusted R2 = 1, P < 0.001) and post-PPCI CFV was found to be an independent predictor of post-STEMI HF (adjusted hazard ratio: 0.61, 95% confidence interval: 0.41-0.90, P = 0.012). The area under curve estimate of the multivariable regression model was 0.749.ConclusionsCFV is an integrated coronary physiological assessment approach that incorporates epicardial and microcirculatory contributions. Patients with post-PPCI CFV < 17.4 cm/s were strongly associated with a high risk for post-STEMI HF, even achieving thrombolysis in myocardial infarction grade 3 flow. The immediate angio-based coronary functional assessment is a feasible tool for evaluating suboptimal perfusion and risk stratification.

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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