Rapid fall in circulating non‐classical monocytes in ST elevation myocardial infarction patients correlates with cardiac injury

Marsh, Sarah; Park, Catherine; Redgrave, Rachael; Singh, Ekta; Draganova, Lilia; Boag, Stephen; Spray, Luke; Ali, Simi; Spyridopoulos, Ioakim; Arthur, Helen

doi:10.1096/fj.202100240r

Cited by 12 publications

(9 citation statements)

References 38 publications

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“… 9 Moreover, as early as 90 minutes following reperfusion, anti‐inflammatory monocytes are preferentially depleted in the circulation of patients with ST‐segment–elevation MI, and the rapid fall in anti‐inflammatory monocytes correlates with larger infarct size and lower LV ejection fraction (LVEF). 10 Taken together, these findings suggest that the systemic increase in proinflammatory monocyte levels has the capacity to exacerbate IRI in humans. It is, however, important to note that the definitions of proinflammatory and anti‐inflammatory monocyte and macrophage markers are controversial.…”

Section: Immune Cell Dynamics After MI and Reperfu...mentioning

confidence: 85%

“… 4 , 11 , 18 Reperfusion further promotes rapid monocyte infiltration during this stage. 10 After recruitment to areas of myocardial damage, monocytes differentiate into proinflammatory macrophages that clear necrotic cells and break down the extracellular matrix in the infarct zone. Myocardial macrophage numbers peak at around 3 days after reperfusion (Figure 2 ).…”

Section: Immune Cell Dynamics After MI and Reperfu...mentioning

confidence: 99%

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Impact of Reperfusion on Temporal Immune Cell Dynamics After Myocardial Infarction

Zhang¹,

Cochran²,

Thomas³

et al. 2023

JAHA

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Excessive inflammation and impaired healing of cardiac tissue following a myocardial infarction (MI) can drive the development of heart failure. Cardiac repair begins immediately after the onset of MI and continues for months. The repair process can be divided into the following 3 overlapping phases, each having distinct functions and sequelae: the inflammatory phase, the proliferative phase, and the maturation phase. Macrophages, neutrophils, and lymphocytes are present in the myocardium throughout the repair process and govern the duration and function of each of these phases. However, changes in the functions of these cell types across each phase are poorly characterized. Numerous immunomodulatory therapies that specifically target inflammation have been developed for promoting cardiac repair and preventing heart failure after MI. However, these treatments have been largely unsuccessful in large‐scale clinical randomized controlled trials. A potential explanation for this failure is the lack of a thorough understanding of the time‐dependent evolution of the functions of immune cells after a major cardiovascular event. Failure to account for this temporal plasticity in cell function may reduce the efficacy of immunomodulatory approaches that target cardiac repair. This review is concerned with how the functions of different immune cells change with time following an MI. Improved understanding of the temporal changes in immune cell function is important for the future development of effective and targeted treatments for preventing heart failure after MI.

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Section: Immune Cell Dynamics After MI and Reperfu...mentioning

confidence: 85%

Section: Immune Cell Dynamics After MI and Reperfu...mentioning

confidence: 99%

Impact of Reperfusion on Temporal Immune Cell Dynamics After Myocardial Infarction

Zhang¹,

Cochran²,

Thomas³

et al. 2023

JAHA

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“…Tamoxifen treatment (2mg/day) was given in adults (age 10-12 weeks) by intraperitoneal injection for 5 consecutive days and 14 days prior to surgery. Surgery to induce a 60 minute transient occlusion of left anterior descending (LAD) artery for 60 minutes was performed under isoflurane anaesthetic as previously described 25,26 , except that pre-surgical sedative/analgesia was provided by subcutaneous injection of midazolam (5mg/Kg) and fentanyl (0.05mg/Kg). Sham controls had the same surgery but without coronary artery ligation.…”

Section: Mouse Surgerymentioning

confidence: 99%

“…Hearts were harvested at 24 hours post reperfusion and heart cryosections (10 µm) were processed for immunofluorescent staining as previously described 26,27 . All staining analyses were blinded to treatment group.…”

Section: Area Of Infarct and Density Of Infiltratementioning

confidence: 99%

“…To investigate the effect of TGFβ1 on pathological changes in heart tissue following myocardial infarction, we used our established surgical mouse model of cardiac ischaemia-reperfusion 25,26 . First we showed that intravenous delivery of recombinant TGFβ1 at the acute phase of ischaemia/reperfusion reduced infarct size at 24h by 30% (p=0.025), based on cell viability staining with triphenyl tetrazolium chloride (TTC) (Figure 2A,B).…”

Section: Exogenous Tgfβ1 Reduces Infarct Size and Inflammatory Respon...mentioning

confidence: 99%

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Exogenous TGFβ1 and its mimic HpTGM attenuate the heart’s inflammatory response to ischaemic injury and improve long term cardiac outcomes

Redgrave

Singh

Tual‐Chalot

et al. 2023

Preprint

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RationaleSuccessful and timely coronary reperfusion following acute ST-elevation myocardial infarction (STEMI) is standard therapy to salvage transiently ischaemic heart muscle. However, the subsequent inflammatory response within the infarct can lead to further loss of viable myocardium. Robust interventions are required in the acute MI setting to minimise cardiac injury and reduce risk of further detrimental progression.ObjectiveTGFβ1 is an anti-inflammatory cytokine released endogenously in response to infection or tissue injury. The goal of this study was to investigate its protective effects when given exogenously following myocardial infarction.Methods and ResultsTGFβ1 is found at increased levels in the blood of STEMI patients immediately following myocardial infarction. We observe a significant correlation (p=0.003) between higher circulating TGFβ1 levels at 24h post MI and a reduction in infarct size over the following 3 months, suggesting that an early increase in circulating TGFβ1 is protective in these patients. Using a mouse model of cardiac ischaemia-reperfusion we demonstrate that additional exogenous TGFβ1 delivered in the acute setting has multiple beneficial outcomes. At 24 hours post-reperfusion It leads to a significantly smaller infarct size (30% reduction, p=0.025), reduced inflammatory infiltrate (28% reduction, p=0.015), lower intra-cardiac expression of inflammatory cytokines IL1β and CCL2 (>50 % reduction, p=0.038 and 0.0004, respectively) and reduced scar size at 4 weeks (21% reduction, p=0.015). Furthermore exogenous delivery of an equivalent dose of HpTGM, a recently described low-fibrogenic mimic of TGFβ1, secreted by a helminth parasite to evade immune rejection, has an almost identical protective effect on injured mouse hearts. Furthermore using a genetic approach we show the benefit is mediated by the vascular endothelium.ConclusionsThis work reveals the potential of exogenous TGFβ1 and HpTGM delivered in the acute MI setting to provide protective anti-inflammatory effects and reduce infarct size, leading to a smaller scar and reduced detrimental progression.

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Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease

Zhang,

Jia,

Guo

et al. 2024

Advanced Science

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Kawasaki disease (KD) is a severe acute febrile illness and systemic vasculitis that causes coronary artery aneurysms in young children. Platelet hyperreactivity and an aberrant immune response are key indicators of KD; however, the mechanism by which hyperactive platelets contribute to inflammation and vasculopathy in KD remains unclear. A cytokine‐mediated positive feedback loop between KD platelets and monocytes is identified. KD platelet–monocyte aggregates (MPAs) are mediated by an initial interaction of P‐selectin (cluster of differentiation 62P, CD62p) and its glycoprotein ligand 1 (PSGL‐1). This is followed by a coordinated interaction of platelet glycoprotein (GP)Ibα with monocyte CD11b. Monocyte‐activated platelets initiate transforming growth factor (TGF)β1 release, which results in nuclear localization of nuclear factor kappaB in monocytes, therefore, driving the phenotypic conversion of classical monocytes (CD14+CD16−) into proinflammatory monocytes (CD14+CD16+). The platelet‐activated monocytes release interleukin‐1 and tissue necrotic factor‐α, which promote further platelet activation. KD‐induced inflammation and vasculopathy are prevented by inhibiting the components of this positive feedback loop. Notably, mice deficient in platelet TGFβ1 show less MPA and CD14+CD16+ monocytes, along with reduced inflammation and vasculopathy. These findings reveal that platelet–monocyte interactive proteins (CD62p/PSGL‐1 and (GP)Ibα/CD11b) and cytokine mediators (platelet TGFβ1) are potential biomarkers and therapeutic targets for KD vasculopathy.

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Rapid fall in circulating non‐classical monocytes in ST elevation myocardial infarction patients correlates with cardiac injury

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 12 publications

References 38 publications

Impact of Reperfusion on Temporal Immune Cell Dynamics After Myocardial Infarction

Impact of Reperfusion on Temporal Immune Cell Dynamics After Myocardial Infarction

Exogenous TGFβ1 and its mimic HpTGM attenuate the heart’s inflammatory response to ischaemic injury and improve long term cardiac outcomes

Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease

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