Publications by authors named "Milka Koupenova"

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.

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  • COVID-19 causes abnormal blood clotting and thrombosis that can increase death rates, with platelets playing a critical role by responding quickly to the virus and facilitating coagulation.
  • Research shows the SARS-CoV-2 virus interacts with platelets, confirmed by the presence of viral genes and antibodies, which triggers immune responses and may lead to programmed cell death in platelets.
  • The review explores how platelet activation relates to severe COVID-19 outcomes, potential activation by viral proteins, and existing animal models to better understand these mechanisms in living organisms.
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The traditional role of platelets is in the formation of blood clots for physiologic (e.g., in hemostasis) or pathologic (e.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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Article Synopsis
  • Platelets are crucial, non-nucleated blood components that play a major role in regulating hemostasis and thrombosis, impacting conditions like heart attacks and strokes.
  • Their interactions with blood vessels are being studied to better understand how they communicate environmental changes to other blood cells.
  • Beyond clotting, platelets also participate in immune responses to infections, balancing their roles between causing and regulating inflammation and clot formation.
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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.

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  • Lysyl oxidase (LOX) is found to be overexpressed in conditions like arterial stenosis and myeloproliferative neoplasms (MPNs), with elevated levels in both mouse models and patients.
  • Transgenic mice engineered to express LOX specifically in megakaryocytes and platelets (Pf4-Lox(tg/tg)) showed a significant reduction in time to vessel occlusion after injury, indicating increased thrombus formation tendency.
  • The study reveals that LOX enhances platelet activation by improving adhesion to collagen and amplifying their aggregation response, suggesting its role in thrombosis via the collagen receptor integrin α2β1.
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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.

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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.

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  • Viral infections can lead to lower platelet counts, and this study reveals that the encephalomyocarditis virus (EMCV) triggers this drop primarily through platelet Toll-like receptor 7 (TLR7).
  • TLR7 activation causes platelets to form large aggregates with neutrophils, leading to the internalization of platelet fragments by neutrophils without affecting platelet clotting ability.
  • The research indicates that TLR7's role in platelet responses to viral infections can affect overall survival, showing that this interaction between platelets and viruses goes beyond just clotting functions.
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