Dataset Information

High-throughput 13-parameter immunophenotyping identifies shifts in the circulating T-cell compartment following reperfusion in patients with acute myocardial infarction.

ABSTRACT:

Rationale

With the advent of primary PCI (PPCI), reperfusion is achieved in almost all patients presenting with acute myocardial infarction. However, despite multiple trials, reperfusion injury has not been successfully dealt with so far. In mouse models, CD4(+) T lymphocytes (T cells) have been shown to be crucial instigators of reperfusion injury.

Objective

Our goal was to investigate the role of CD4(+) T cells during myocardial reperfusion following PPCI by developing a protocol for high-throughput multiplexed flow cytometric analysis and multivariate flow clustering.

Methods and results

13-parameter immunophenotyping and hierarchical cluster analysis (HCA) identified a unique CD4(+)CD57(+) T-cell population in PPCI patients that reflected acute proliferation in the CD4(+) T-cell compartment. CD4(+)CCR7(+) T cells were specifically depleted from peripheral blood during the first 30 min of myocardial reperfusion after PPCI, suggesting a potential role for the chemokine receptor CCR7 in T-cell redistribution to either peripheral tissues or migration to the infarcted heart during ischemia/reperfusion following PPCI.

Conclusions

High-throughput polychromatic flow cytometry and HCA are capable of objective, time and cost efficient assessment of the individual T-cell immune profile in different stages of coronary heart disease and have broad applications in clinical trials.

SUBMITTER: Hoffmann J

PROVIDER: S-EPMC3473067 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

High-throughput 13-parameter immunophenotyping identifies shifts in the circulating T-cell compartment following reperfusion in patients with acute myocardial infarction.

Hoffmann Jedrzej J Fiser Karel K Weaver Jolanta J Dimmick Ian I Loeher Monika M Pircher Hanspeter H Martin-Ruiz Carmen C Veerasamy Murugapathy M Keavney Bernard B von Zglinicki Thomas T Spyridopoulos Ioakim I

PloS one 20121016 10

<h4>Rationale</h4>With the advent of primary PCI (PPCI), reperfusion is achieved in almost all patients presenting with acute myocardial infarction. However, despite multiple trials, reperfusion injury has not been successfully dealt with so far. In mouse models, CD4(+) T lymphocytes (T cells) have been shown to be crucial instigators of reperfusion injury.<h4>Objective</h4>Our goal was to investigate the role of CD4(+) T cells during myocardial reperfusion following PPCI by developing a protoco ...[more]

PMID: 23077561

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Project description:BackgroundMyocardial damage due to acute ST-segment elevation myocardial infarction (STEMI) remains a significant global health problem. New approaches to limit myocardial infarct size and reduce progression to heart failure after STEMI are needed. Mechanically reducing left ventricular (LV) workload (LV unloading) before coronary reperfusion is emerging as a potential approach to reduce infarct size.ObjectivesGiven the central importance of mitochondria in reperfusion injury, we hypothesized that compared with immediate reperfusion (IR), LV unloading before reperfusion improves myocardial energy substrate use and preserves mitochondrial structure and function.MethodsTo explore the effect of LV unloading duration on infarct size, we analyzed data from the STEMI-Door to Unload (STEMI-DTU) trial and then tested the effect of LV unloading on ischemia and reperfusion injury, cardiac metabolism, and mitochondrial function in swine models of acute myocardial infarction.ResultsThe duration of LV unloading before reperfusion was inversely associated with infarct size in patients with large anterior STEMI. In preclinical models, LV unloading reduced the expression of hypoxia-sensitive proteins and myocardial damage due to ischemia alone. LV unloading with a transvalvular pump (TV-P) but not with venoarterial extracorporeal membrane oxygenation (ECMO) reduced infarct size. Using unbiased and blinded metabolic profiling, TV-P improved myocardial energy substrate use and preserved mitochondrial structure including cardiolipin content after reperfusion compared with IR or ECMO. Functional testing in mitochondria isolated from the infarct zone showed an intact mitochondrial structure including cardiolipin content, preserved activity of the electron transport chain including mitochondrial complex I, and reduced oxidative stress with TV-P-supported reperfusion but not with IR or ECMO.ConclusionsThese novel findings identify that transvalvular unloading limits ischemic injury before reperfusion, improves myocardial energy substrate use, and preserves mitochondrial structure and function after reperfusion.

Dataset Information

High-throughput 13-parameter immunophenotyping identifies shifts in the circulating T-cell compartment following reperfusion in patients with acute myocardial infarction.

Rationale

Objective

Methods and results

Conclusions

Publications

High-throughput 13-parameter immunophenotyping identifies shifts in the circulating T-cell compartment following reperfusion in patients with acute myocardial infarction.

Similar Datasets

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