Emerging roles of neutrophil-borne S100A8/A9 in cardiovascular inflammation

Sreejit, Gopalkrishna; Latif, Ahmed Abdel; Murphy, Andrew; Nagareddy, Prabhakara R

doi:10.1016/j.phrs.2020.105212

Cited by 42 publications

(34 citation statements)

References 147 publications

(172 reference statements)

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“…From the cell cluster analysis, we can note that almost all S100a8 and S100a9 were from neutrophils ( Figure 3 A,D). Researchers reported that neutrophils are the main source of S100a8/a9, which have become the treatment targets of cardiac inflammation and the following damage [ 39 , 40 , 41 ]. Using scRNA sequencing, we found that S100a8, S100a9, and neutrophils changed in synchrony, further elucidating that S100a8 and S100a9 were derived from neonatal neutrophils in the early stage of MI rather than resident neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis Reveals S100a8/a9 Regulates Autophagy and Apoptosis through the MAPK and PI3K-AKT Signaling Pathway in the Early Stage of Myocardial Infarction

Zhu

Hou

et al. 2022

Cells

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Myocardial infarction (MI), a type of coronary heart disease, has had a significantly increased incidence in recent years. The balance of cardiomyocyte apoptosis and autophagy after MI is one of the main determinants of patient prognosis. Both affect myocardial fibrosis and ventricular remodeling and regulate cell survival. However, there are few studies on the regulation mechanism of cardiomyocyte autophagy and apoptosis in the early stage after MI. In this study, based on analyzing the scRNA-seq and mRNA-seq data of mice in the early stage of MI, we found that the expression of S100a8 and S100a9 increased first and then decreased in the early stage of MI, and their expression level changed with the number of neutrophils. Further, through the functional enrichment analysis of the differentially expressed genes, we found that S100a8 and S100a9 were simultaneously associated with autophagy and apoptosis and could regulate autophagy and apoptosis of cardiomyocytes through MAPK or PI3K-AKT signaling pathways. This study provides valuable insights for clarifying the pathogenesis of early stage MI and improving its early treatment.

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Section: Discussionmentioning

confidence: 99%

Integrated Analysis Reveals S100a8/a9 Regulates Autophagy and Apoptosis through the MAPK and PI3K-AKT Signaling Pathway in the Early Stage of Myocardial Infarction

Zhu

Hou

et al. 2022

Cells

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“…MI enhances granulopoiesis, resulting in the increased production of neutrophils in the bone marrow [ 1 , 69 ]. Following infection or sterile inflammation (e.g., MI), granulopoiesis can be enhanced by DAMPs and inflammatory cytokines (e.g., IL-6, IL-3, and granulocyte-macrophage colony-stimulating factor) [ 1 , 70 ]. A seminal study shows that neutrophils can induce granulopoiesis [ 71 ].…”

Section: Neutrophil-mediated Cardiac Injurymentioning

confidence: 99%

Role of Neutrophils in Cardiac Injury and Repair Following Myocardial Infarction

2021

Cells

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Neutrophils are first-line responders of the innate immune system. Following myocardial infarction (MI), neutrophils are quickly recruited to the ischemic region, where they initiate the inflammatory response, aiming at cleaning up dead cell debris. However, excessive accumulation and/or delayed removal of neutrophils are deleterious. Neutrophils can promote myocardial injury by releasing reactive oxygen species, granular components, and pro-inflammatory mediators. More recent studies have revealed that neutrophils are able to form extracellular traps (NETs) and produce extracellular vesicles (EVs) to aggravate inflammation and cardiac injury. On the contrary, there is growing evidence showing that neutrophils also exert anti-inflammatory, pro-angiogenic, and pro-reparative effects, thus facilitating inflammation resolution and cardiac repair. In this review, we summarize the current knowledge on neutrophils’ detrimental roles, highlighting the role of recently recognized NETs and EVs, followed by a discussion of their beneficial effects and molecular mechanisms in post-MI cardiac remodeling. In addition, emerging concepts about neutrophil diversity and their modulation of adaptive immunity are discussed.

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“…Chronic inflammation is also pathogenically pivotal and therapeutically relevant in CVD (Everett et al, 2019). Among the stress‐secreted factors, the danger‐associated molecular pattern (DAMP) alarmins S100A8 and S100A9 have been associated with cardiac dysfunction (Sallman & List, 2019; Schiopu & Cotoi, 2013; Sreejit et al, 2020). Nonetheless, it remains unknown whether people with signs of physical frailty but still disease‐free, which reportedly represent half of the European citizens aged ≥50 years (Manfredi et al, 2019), exhibit subclinical cardiovascular dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic progenitor cell liabilities and alarmins S100A8/A9‐related inflammaging associate with frailty and predict poor cardiovascular outcomes in older adults

et al. 2022

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Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre‐frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10‐fold) and peripheral blood (>200‐fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multidomain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1‐year follow‐up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro‐inflammatory cytokines in pre‐frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes.

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Emerging roles of neutrophil-borne S100A8/A9 in cardiovascular inflammation

Cited by 42 publications

References 147 publications

Integrated Analysis Reveals S100a8/a9 Regulates Autophagy and Apoptosis through the MAPK and PI3K-AKT Signaling Pathway in the Early Stage of Myocardial Infarction

Integrated Analysis Reveals S100a8/a9 Regulates Autophagy and Apoptosis through the MAPK and PI3K-AKT Signaling Pathway in the Early Stage of Myocardial Infarction

Role of Neutrophils in Cardiac Injury and Repair Following Myocardial Infarction

Hematopoietic progenitor cell liabilities and alarmins S100A8/A9‐related inflammaging associate with frailty and predict poor cardiovascular outcomes in older adults

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