Inflammatory stress-mediated chromatin changes underlie dysfunction in endothelial cells.

Inflammatory stresses underlie endothelial dysfunction and contribute to the development of chronic cardiovascular disorders such as atherosclerosis and vascular fibrosis. The initial transcriptional response of endothelial cells to pro-inflammatory cytokines such as TNF-alpha is well established. However, very few studies uncover the effects of inflammatory stresses on chromatin architecture.

Platelets and SARS-CoV-2 During COVID-19: Immunity, Thrombosis, and Beyond.

COVID-19 is characterized by dysregulated thrombosis and coagulation that can increase mortality in patients. Platelets are fast responders to pathogen presence, alerting the surrounding immune cells and contributing to thrombosis and intravascular coagulation. The SARS-CoV-2 genome has been found in platelets from patients with COVID-19, and its coverage varies according to the method of detection, suggesting direct interaction of the virus with these cells.

Beyond the thrombus: Platelet-inspired nanomedicine approaches in inflammation, immune response, and cancer.

The traditional role of platelets is in the formation of blood clots for physiologic (e.g., in hemostasis) or pathologic (e.

Platelet and Megakaryocyte Roles in Innate and Adaptive Immunity.

Classically, platelets have been described as the cellular blood component that mediates hemostasis and thrombosis. This important platelet function has received significant research attention for >150 years. The immune cell functions of platelets are much less appreciated.

Human Platelets and Influenza Virus: Internalization and Platelet Activation.

Influenza infection has long been associated with prothrombotic outcomes in patients and platelets are the blood component predominantly responsible for thrombosis. In this review, we outline what is known about influenza interaction with human platelets, virion internalization, and viral RNA sensing, and the consequent impact on platelet function. We further discuss activation of platelets by IgG-influenza complexes and touch upon mechanisms of environmental platelet activation that relate to prothrombotic outcomes in patients during infection.

SARS-CoV-2 Initiates Programmed Cell Death in Platelets.

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Yersinia pestis escapes entrapment in thrombi by targeting platelet function.

Background: Platelets are classically recognized for their role in hemostasis and thrombosis. Recent work has demonstrated that platelets can also execute a variety of immune functions. The dual prothrombotic and immunological roles of platelets suggest that they may pose a barrier to the replication or dissemination of extracellular bacteria.

SARS-CoV-2 Receptors are Expressed on Human Platelets and the Effect of Aspirin on Clinical Outcomes in COVID-19 Patients.

Coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of anti-platelet agents in attenuating thrombosis is unknown. We aimed to determine if human platelets express the known SARS-CoV-2 receptor-protease axis on their cell surface and assess whether the anti-platelet effect of aspirin may mitigate risk of myocardial infarction (MI), cerebrovascular accident (CVA), and venous thromboembolism (VTE) in COVID-19.

A Translational Model for Venous Thromboembolism: MicroRNA Expression in Hibernating Black Bears.

Background: Hibernating American black bears have significantly different clotting parameters than their summer active counterparts, affording them protection against venous thromboembolism during prolonged periods of immobility. We sought to evaluate if significant differences exist between the expression of microRNAs in the plasma of hibernating black bears compared with their summer active counterparts, potentially contributing to differences in hemostasis during hibernation.

Materials And Methods: MicroRNA sequencing was assessed in plasma from 21 American black bears in summer active (n = 11) and hibernating states (n = 10), and microRNA signatures during hibernating and active state were established using both bear and human genome.

Potential role of platelets in COVID-19: Implications for thrombosis.

For the past 150 years, platelets have been recognized as the major blood component that mediates hemostasis and thrombosis. In more recent years, however, we have come to appreciate that platelets also perform profound immune functions during infection with various pathogens. We now recognize that platelets can also mediate a response to various RNA viruses such as influenza and that many viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can affect platelet count.

Pollen-derived RNAs Are Found in the Human Circulation.

The presence of nonhuman RNAs in man has been questioned and it is unclear if food-derived miRNAs cross into the circulation. In a large population study, we found nonhuman miRNAs in plasma by RNA sequencing and validated a small number of pine-pollen miRNAs by RT-qPCR in 2,776 people. The presence of these pine-pollen miRNAs associated with hay fever and not with overt cardiovascular or pulmonary disease.

The role of platelets in mediating a response to human influenza infection.

Influenza infection increases the incidence of myocardial infarction but the reason is unknown. Platelets mediate vascular occlusion through thrombotic functions but are also recognized to have immunomodulatory activity. To determine if platelet processes are activated during influenza infection, we collected blood from 18 patients with acute influenza infection.

Micro RNAs from DNA Viruses are Found Widely in Plasma in a Large Observational Human Population.

Viral infections associate with disease risk and select families of viruses encode miRNAs that control an efficient viral cycle. The association of viral miRNA expression with disease in a large human population has not been previously explored. We sequenced plasma RNA from 40 participants of the Framingham Heart Study (FHS, Offspring Cohort, Visit 8) and identified 3 viral miRNAs from 3 different human Herpesviridae.

Biology of Platelet Purinergic Receptors and Implications for Platelet Heterogeneity.

Platelets are small anucleated cells present only in mammals. Platelets mediate intravascular hemostatic balance, prevent interstitial bleeding, and have a major role in thrombosis. Activation of platelet purinergic receptors is instrumental in initiation of hemostasis and formation of the hemostatic plug, although this activation process becomes problematic in pathological settings of thrombosis.

Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis.

Platelets, non-nucleated blood components first described over 130 years ago, are recognized as the primary cell regulating hemostasis and thrombosis. The vascular importance of platelets has been attributed to their essential role in thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism. Increasing knowledge on the platelets' role in the vasculature has led to many advances in understanding not only how platelets interact with the vessel wall but also how they convey changes in the environment to other circulating cells.

Thrombosis and platelets: an update.

Haemostasis and thrombosis are complex, multifactorial processes. There is an evolving understanding of the mechanisms influencing vascular occlusion and the role of inflammation and immunity. Despite major advances in elucidating the mechanistic pathways mediating platelet function and thrombosis, challenges in the treatment of vascular occlusive diseases persist.

Lysyl oxidase is associated with increased thrombosis and platelet reactivity.

Lysyl oxidase (LOX) is overexpressed in various pathologies associated with thrombosis, such as arterial stenosis and myeloproliferative neoplasms (MPNs). LOX is elevated in the megakaryocytic lineage of mouse models of MPNs and in patients with MPNs. To gain insight into the role of LOX in thrombosis and platelet function without compounding the influences of other pathologies, transgenic mice expressing LOX in wild-type megakaryocytes and platelets (Pf4-Lox(tg/tg)) were generated.

Sex differences in platelet toll-like receptors and their association with cardiovascular risk factors.

Objective: Platelets contribute to thrombosis, and platelet toll-like receptors (TLRs) are central in pathogen detection, potentially mediating infection-induced vascular occlusion. Using a large community-based cohort study, we sought to examine if platelets express all known TLR transcripts and analyze their association with cardiovascular risk factors.

Approach And Results: mRNA levels for TLRs were measured in isolated platelets by high-throughput quantitative reverse transcriptase polymerase chain reaction in 1625 participants (mean age, 66.

The macrophage A2B adenosine receptor regulates tissue insulin sensitivity.

High fat diet (HFD)-induced type 2 diabetes continues to be an epidemic with significant risk for various pathologies. Previously, we identified the A2b adenosine receptor (A2bAR), an established regulator of inflammation, as a regulator of HFD-induced insulin resistance. In particular, HFD was associated with vast upregulation of liver A2bAR in control mice, and while mice lacking this receptor showed augmented liver inflammation and tissue insulin resistance.

Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis.

Viral infections have been associated with reduced platelet counts, the biological significance of which has remained elusive. Here, we show that infection with encephalomyocarditis virus (EMCV) rapidly reduces platelet count, and this response is attributed to platelet Toll-like receptor 7 (TLR7). Platelet-TLR7 stimulation mediates formation of large platelet-neutrophil aggregates, both in mouse and human blood.