Platelet–Leucocyte Aggregates as Novel Biomarkers in Cardiovascular Diseases

Pluta, Kinga; Porębska, Kinga; Urbanowicz, Tomasz; Olasińska-Wiśniewska, Anna; Targoński, Radosław; Krasińska, Aleksandra; Filipiak‬, Krzysztof J.; Jemielity, Marek; Krasiński, Zbigniew

doi:10.3390/biology11020224

Cited by 22 publications

(14 citation statements)

References 183 publications

(337 reference statements)

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“…According to experimental evidence, the “regulation of angiogenesis” is involved in plaque formation [ 89 ] and may cause many diseases such as cardiovascular disease and diabetic microvascular complications [ 90 ]. Research consistently showed that regardless of disease severity, “leukocyte aggregation” is an independent indicator of future cardiovascular outcomes, and it has been investigated extensively as a biomarker in cardiovascular diseases [ 91 , 92 ]. Chemokines are small chemotactic cytokines that trigger integrin activation to induce firm arrest of leukocytes on activated endothelium, thus “positive regulation of chemokine production” contributing to the development of atherosclerosis [ 93 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics and System Biological Approaches for the Identification of Genetic Risk Factors in the Progression of Cardiovascular Disease

Barua

Omit

Rana

et al. 2022

Cardiovascular Therapeutics

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Background. Cardiovascular disease (CVD) is the combination of coronary heart disease, myocardial infarction, rheumatic heart disease, and peripheral vascular disease of the heart and blood vessels. It is one of the leading deadly diseases that causes one-third of the deaths yearly in the globe. Additionally, the risk factors associated with it make the situation more complex for cardiovascular patients, which lead them towards mortality, but the genetic association between CVD and its risk factors is not clearly explored in the global literature. We addressed this issue and explored the linkage between CVD and its risk factors. Methods. We developed an analytical approach to reveal the risk factors and their linkages with CVD. We used GEO microarray datasets for the CVD and other risk factors in this study. We performed several analyses including gene expression analysis, diseasome analysis, protein-protein interaction (PPI) analysis, and pathway analysis for discovering the relationship between CVD and its risk factors. We also examined the validation of our study using gold benchmark databases OMIM, dbGAP, and DisGeNET. Results. We observed that the number of 32, 17, 53, 70, and 89 differentially expressed genes (DEGs) is overlapped between CVD and its risk factors of hypertension (HTN), type 2 diabetes (T2D), hypercholesterolemia (HCL), obesity, and aging, respectively. We identified 10 major hub proteins (FPR2, TNF, CXCL8, CXCL1, IL1B, VEGFA, CYBB, PTGS2, ITGAX, and CCR5), 12 significant functional pathways, and 11 gene ontological pathways that are associated with CVD. We also found the connection of CVD with its risk factors in the gold benchmark databases. Our experimental outcomes indicate a strong association of CVD with its risk factors of HTN, T2D, HCL, obesity, and aging. Conclusions. Our computational approach explored the genetic association of CVD with its risk factors by identifying the significant DEGs, hub proteins, and signaling and ontological pathways. The outcomes of this study may be further used in the lab-based analysis for developing the effective treatment strategies of CVD.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics and System Biological Approaches for the Identification of Genetic Risk Factors in the Progression of Cardiovascular Disease

Barua

Omit

Rana

et al. 2022

Cardiovascular Therapeutics

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“…The binding of P-selectin on platelets to leukocyte (mostly monocyte) surface PSGL-1 (P-selectin glycoprotein ligand) is an important event that enhances monocyte activation. In addition, this binding increases αMβ2 integrin (Mac-1, CD11b/CD18) expression, which stabilizes the complex and is crucial for the survival of circulating MPAs [ 23 , 27 ]. Our previous study observed an obvious increase of CD11b expression in MPA-mediated monocytes [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Papain ameliorates monocyte-platelet aggregate formation-mediated inflammatory responses in monocytes by upregulating miRNA-146a transcription

et al. 2022

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Background MicroRNA-146a (miRNA-146a) is a nuclear factor κB (NF-κB)-inducible and inflammation-sensitive miRNA, while papain elicits anti-inflammatory effects by inhibiting monocyte-platelet aggregate (MPA)-mediated NF-κB pathway activation in monocytes. This study aimed to demonstrate the underlying effects of papain on MPA formation-initiated miRNA-146a expression and subsequent action in monocytes. Methods THP-1 cells were exposed to papain, miRNA-146a mimic and inhibitor, NF-κB inhibitor (BAY11-7082), and platelets. Flow cytometry was used to measure the MPA formation-initiated monocyte activation. Levels of miRNA-146a, cyclooxygenase 2 (COX-2) mRNA and protein, and monocyte chemoattractant protein 1 (MCP-1) were analyzed in monocytes by RT-PCR, western blot, and ELISA. Results The NF-κB inhibitor and miRNA-146a mimics upregulated miRNA-146a expression but suppressed subsequent monocyte activation and expression of COX-2 and MCP-1. Following exposure to papain, the enhanced miRNA-146a transcription induced by MPA-formation was found along with significant inhibition of monocyte activation in a dose-dependent manner. However, the inhibitory tendency was significantly reversed by miRNA-146a inhibitors. Expression of COX-2 mRNA and protein, as well as MCP-1, was inhibited in monocytes by papain, whereas miRNA-146a inhibitors promoted COX-2 and MCP-1 expression. Conclusion Our findings suggest that papain can inhibit MPA formation-mediated expression of inflammatory mediators in activated monocytes by upregulating miRNA-146a transcription.

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“…The formation of platelet-leukocyte aggregates mediates outside-in signaling events and, thus, facilitates leukocyte migration and function [ 10 ]. Leukocytes may bind a varying number of platelets and complexes may appear either unbound in the circulation or bound to vessel walls and tissues [ 85 ]. Flow cytometry, tissue section imaging and live cell imaging represent the most common tools to analyze platelet leukocyte aggregates by applying specific fluorescent antibodies to identify different cell populations [ 86 ].…”

Section: Immune-modulatory Function Of Plateletsmentioning

confidence: 99%

“…A growing body of literature has examined platelet–leukocyte interactions under disease conditions, indicating their prominent role for a comprehensive immune response. In addition, platelet–leukocyte aggregates have been suggested as potential biomarkers in various pathologies including pulmonary diseases, vasculitis and cardiovascular diseases [ 85 ].…”

Section: Immune-modulatory Function Of Plateletsmentioning

confidence: 99%

Platelets at the Crossroads of Pro-Inflammatory and Resolution Pathways during Inflammation

Ludwig

Hilger

Zarbock

et al. 2022

Cells

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Platelets are among the most abundant cells in the mammalian circulation. Classical platelet functions in hemostasis and wound healing have been intensively explored and are generally accepted. During the past decades, the research focus broadened towards their participation in immune-modulatory events, including pro-inflammatory and, more recently, inflammatory resolution processes. Platelets are equipped with a variety of abilities enabling active participation in immunological processes. Toll-like receptors mediate the recognition of pathogens, while the release of granule contents and microvesicles promotes direct pathogen defense and an interaction with leukocytes. Platelets communicate and physically interact with neutrophils, monocytes and a subset of lymphocytes via soluble mediators and surface adhesion receptors. This interaction promotes leukocyte recruitment, migration and extravasation, as well as the initiation of effector functions, such as the release of extracellular traps by neutrophils. Platelet-derived prostaglandin E2, C-type lectin-like receptor 2 and transforming growth factor β modulate inflammatory resolution processes by promoting the synthesis of pro-resolving mediators while reducing pro-inflammatory ones. Furthermore, platelets promote the differentiation of CD4+ T cells in T helper and regulatory T cells, which affects macrophage polarization. These abilities make platelets key players in inflammatory diseases such as pneumonia and the acute respiratory distress syndrome, including the pandemic coronavirus disease 2019. This review focuses on recent findings in platelet-mediated immunity during acute inflammation.

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Platelet–Leucocyte Aggregates as Novel Biomarkers in Cardiovascular Diseases

Cited by 22 publications

References 183 publications

Bioinformatics and System Biological Approaches for the Identification of Genetic Risk Factors in the Progression of Cardiovascular Disease

Bioinformatics and System Biological Approaches for the Identification of Genetic Risk Factors in the Progression of Cardiovascular Disease

Papain ameliorates monocyte-platelet aggregate formation-mediated inflammatory responses in monocytes by upregulating miRNA-146a transcription

Platelets at the Crossroads of Pro-Inflammatory and Resolution Pathways during Inflammation

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