Cargo-free particles divert neutrophil-platelet aggregates to reduce thromboinflammation

Banka, Alison; Guevara, Maria Valentina; Brannon, Emma R.; Nguyen, Nhien; Song, Shuang; Cady, Gillian; Pinsky, David J.; Uhrich, Kathryn E.; Adili, Reheman; Holinstat, Michael; Eniola‐Adefeso, Omolola

doi:10.1038/s41467-023-37990-z

Cited by 8 publications

(5 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, ruptured IA had more neutrophils, which may be associated with IA rupture and subsequent local thrombosis. 15 , 42 Notably, ssGSEA analysis disclosed that neutrophil infiltration occurred at the stage of IA formation and the number of neutrophils increased when IA ruptured based on the marker genes uniquely expressed by neutrophils (Fig. 1E , Table S1 ).…”

Section: Resultsmentioning

confidence: 97%

Decoding the biology and clinical implication of neutrophils in intracranial aneurysm

Ji,

Han,

Danyang Jie

et al. 2024

Ann Clin Transl Neurol

View full text Add to dashboard Cite

ObjectiveAbundant neutrophils have been identified in both ruptured and unruptured intracranial aneurysm (IA) domes, with their function and clinical implication being poorly characterized.Materials and MethodsWe employed single‐cell RNA sequencing (scRNA‐Seq) datasets of both human and murine model, and external bulk mRNA sequencing datasets to thoroughly explore the features and functional heterogeneous of neutrophils infiltrating the IA dome.ResultsWe found that both unruptured and ruptured IA dome contain a substantial population of neutrophils, characterized by FCGR3B, G0S2, CSF3R, and CXCR2. These cells exhibited heterogeneity in terms of function and differentiation. Despite similar transcriptional activation, neutrophils in IA dome expressed a repertoire of gene programs that mimicked transcriptomic alterations observed from bone marrow to peripheral blood, showing self‐similarity. In addition, the recruitment of neutrophils in unruptured IA was primarily mediated by monocytes/macrophages, and once ruptured, both neutrophils, and a specific subset of inflammatory smooth muscle cells (SMCs) were involved in the process. The receiver operator characteristic curve (ROC) analysis indicated that distinct neutrophil subclusters were associated with IA formation and rupture, respectively. By reviewing current studies, we found that neutrophils play a detrimental role to IA wall integrity through secreting specific ligands, ferroptosis driven by ALOX5AP and PTGS2, and the formation of neutrophil extracellular traps (NETs) mediated by PADI4.InterpretationThis study delineated the biology and potential clinical implications of neutrophils in IA dome and provided a reliable basis for future researches.

show abstract

Section: Resultsmentioning

confidence: 97%

Decoding the biology and clinical implication of neutrophils in intracranial aneurysm

Ji,

Han,

Danyang Jie

et al. 2024

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…NK cells also induce immune cell apoptosis with their ligands, ultimately reducing pathogen uptake and clearance (Michel et al, 2012;Thorén et al, 2012). The activated endothelium also increases its expression of adhesion molecules, including von Willebrand factor (vWF), P-selectins, vascular cell adhesion molecule-1 (VCAM-1), and platelet-endothelial cell adhesion molecule (PECAM)-1 (Greineder et al, 2013;Banka et al, 2023). These molecules enhance the binding of neutrophils, monocytes, and platelets, promoting coagulation and providing targets for sitespecific nanoparticles.…”

Section: Biomaterials For Inflammationmentioning

confidence: 99%

“…As sepsis worsens, it can progress to thromboinflammation, which involves the inappropriate and unregulated formation of blood clots due to an extreme immune response (Banka et al, 2023). In more detail, inflammation activates the complement system and induces thrombosis (Vagionas et al, 2022).…”

Section: Biomaterials For Thromboinflammationmentioning

confidence: 99%

“…Therefore, there is an urgent need for the development of a single therapeutic that can simultaneously address inflammation, thrombosis, and hemorrhage. To reduce thromboinflammation, studies have shown that cargofree polystyrene microparticles can disrupt leukocyte adhesion to the endothelium in LPS models, emphasizing the importance in biomaterial physical characteristics (Banka et al, 2023) (Figure 3). Specifically, carriers with rod-like shapes and diameters between 2 and 5 microns demonstrate enhanced margination along the endothelium compared to spherical nanoparticles.…”

Section: Biomaterials For Thromboinflammationmentioning

confidence: 99%

See 1 more Smart Citation

Biomaterials for treating sepsis-induced thromboinflammation

Lutz,

Brown

2023

Front. Biomater. Sci.

View full text Add to dashboard Cite

Sepsis is a common and life-threatening disorder with an alarmingly high mortality rate. Unfortunately, this rate has not decreased significantly over the last decade and the number of septic cases is increasing each year. Despite sepsis affecting millions of people annually, there is still not an established standard of care. The development of a therapy that targets the thromboinflammation characteristic of sepsis is imperative. Until recently, research has focused on uncovering individual pathways to target. As more of the pathophysiology of sepsis has become understood and more biomarkers uncovered, the interplay between endothelial cells, platelets, and leukocytes has emerged as a critical event. Therefore, a multi-targeted approach is clearly required for designing an effective treatment for sepsis. The versatility of biomaterials offers a promising solution in that they can be designed to target and affect multiple pathways and systems and safely inhibit excessive inflammation while maintaining hemostasis. Already, studies have demonstrated the ability of biomaterials to target different processes and stages in sepsis-induced inflammation and coagulopathy. Moreover, some biomaterials offer inherent anti-inflammatory and hemostatic qualities. This review aims to discuss the most recent advancements in biomaterial development designed to address inflammation, coagulopathy, and thromboinflammation.

show abstract

“…Ischemic cardiomyocytes activate an intense thromboinflammatory response that primarily involves activated platelets engaging with various cells (Li et al., 2021 ; Schrottmaier et al., 2020 ; Sexton et al., 2015 ). The intricate interplay between various factors triggers the initiation of the coagulation cascade and the subsequent formation of a nascent clot (Banka et al., 2023 ). Another key component that contributes to the formation of blood clots is the reduction in lymphocyte count (Ommen et al., 1997 ).…”

Section: Introductionmentioning

confidence: 99%

Combined use of frontal plane QRS‐T angle and platelet‐to‐lymphocyte ratio in the risk prediction of ischemic cardiomyopathy in STEMI

Colluoglu,

Aksu,

Akın

et al. 2024

Noninvasive Electrocardiol

View full text Add to dashboard Cite

BackgroundFrontal plane QRS‐T angle (fQRS‐T) and platelet‐to‐lymphocyte ratio (PLR) are highly important parameters that well‐predict unfavorable outcomes in patients with ST‐elevated myocardial infarction (STEMI).There are limited data on the predictive significance of ischemic cardiomyopathy (I‐CMP) from the combination of fQRS‐T and PLR in STEMI, compared to using fQRS‐T and PLR alone.AimWe aimed to evaluate the ability of the combination of fQRS‐T and PLR routinely obtained on admission to identify STEMI patients at risk of I‐CMP.MethodSix hundred and thirty‐eight consecutive patients with STEMI who underwent primary percutaneous coronary intervention between 2018 and 2021 were included. The assessment of I‐CMP was conducted through two‐dimentional (2D)‐echocardiography 6 weeks post‐STEMI and I‐CMP was defined as a left ventricular ejection fraction (LVEF) of 50% or less. Multivariate logistic regression analysis and receiver operating curve (ROC) analysis were performed to predict the development of I‐CMP.ResultsIn ROC analysis, the cut‐off values of fQRS‐T and PLR for best predicting I‐CMP were 66.72° and 101.23, respectively. The model using the combination of two markers was the most powerful predictor of I‐CMP risk (OR: 3.183, 95% CI: 1.971–5.139, p = .001) when included in a single variable such as high fQRS‐T or high PLR (OR: 1.422, 95% CI: 0.870–0.232, p = .160). Additionally, the concomitant presence of high fQRS‐T and high PLR exhibited the highest specificity (77%) for I‐CMP relative to the individual presence of high fQRS‐T (66%) or PLR (49%).ConclusionThe combination of fQRS‐T and PLR, which is a simple and cost‐effective risk assessment, may serve as a more reliable prognosticator for I‐CMP as opposed to the use of fQRS‐T and PLR alone for STEMI.

show abstract

Cargo-free particles divert neutrophil-platelet aggregates to reduce thromboinflammation

Cited by 8 publications

References 88 publications

Decoding the biology and clinical implication of neutrophils in intracranial aneurysm

Decoding the biology and clinical implication of neutrophils in intracranial aneurysm

Biomaterials for treating sepsis-induced thromboinflammation

Combined use of frontal plane QRS‐T angle and platelet‐to‐lymphocyte ratio in the risk prediction of ischemic cardiomyopathy in STEMI

Contact Info

Product

Resources

About