Thrombosis models

OBJECTIVES: Protein C (PC) is an anticoagulant that is encoded by the PROC gene. Validation for the function of PC was carried out in mouse models. METHODS: In this study, autosomal recessive PC deficiency (PCD) was selected as the target, and the specific mutation site was chromosome 2 2q13-q14, PROC c.1198G>A (p.Gly400Ser) which targets G399S (GGT to AGC) in mouse models. To investigate the role of hereditary PC in mice models, we used CRISPR/Cas9 gene editing technology to create a mouse model with a genetic PCD mutation...

The unacceptably high stroke rate associated with HeartMate 3 ventricular assist device (VAD) without signs of adherent pump thrombosis is hypothesized to be the result of the emboli produced by the inflow cannula, that are ingested and ejected from the pump. This in vitro and numerical study aimed to emulate the surface features and supraphysiological shear of a ventricular cannula to provide insight into their effect on thrombogenesis. Human whole blood was perfused at calibrated flow rates in a microfluidic channel to achieve shear rates 1000-7500 s-1 , comparable to that experienced on the cannula...

OBJECTIVE: Iliocaval thrombotic obstruction is a challenging condition, especially since thrombus age and corresponding pathological remodeling at presentation are unknown, which directly impacts management. Our aim was to assess the ability of Magnetic Resonance Imaging (MRI) in determining age thresholds of experimentally created inferior vena cava (IVC) thrombosis in pigs. METHODS: We used a previously described swine model of IVC thrombosis. Animals underwent MRI at baseline, immediately after thrombosis creation and after a follow-up period extending from 2 to 28 days...

The health risks associated with combined exposure to microplastics (MPs) and cyanobacteria toxins have gained increasing attention due to the large-scale prevalence of cyanobacterial blooms and accumulation of MPs in aquatic environments. Therefore, we explored the cardiovascular toxic effects of microcystin-LR (MC-LR, 1, 10, 100 μg/L) in the presence of 5 μm polystyrene microplastics (PS-MPs, 100 μg/L) and 80 nm polystyrene nanoplastics (PS-NPs, 100μg/L) in zebrafish models. Embryos were exposed to certain PS-MPs and PS-NPs conditions in water between 3 h post-fertilization (hpf) and 168 hpf...

UNLABELLED: One third of recent non-cirrhotic portal vein thrombosis are associated with local factors. The risk of rethrombosis after anticoagulation withdrawal is unknown. We aimed to determine factors associated with splanchnic or extrasplanchnic new thrombotic events in that setting. METHODS: Retrospective study including recent non-cirrhotic portal vein thrombosis associated with local factors. High and low prothrombotic risk factors, prespecified according to Riport study criteria, were assessed...

INTRODUCTION: A freeze-dried, platelet-derived hemostatic agent (FPH) was developed for acute hemorrhage. The canine product (cFPH) was developed for use in preclinical models supporting human product (hFPH) investigations. MATERIALS AND METHODS: A carotid artery bypass graft (CABG) study in dogs compared 3 dosages of cFPH to canine liquid stored platelets (cLSP) and vehicle (VEH) control groups. Histopathological analysis and blood loss assessments were completed...

BACKGROUND: Bypassing agents are used for breakthrough bleedings in patients with hemophilia A with inhibitor (PwHAwI) receiving emicizumab prophylaxis. Previous study demonstrated a weak binding affinity between emicizumab and factor (F)X (Kd; 1.85 μM), and that this value was much greater than the plasma FX concentration (~130 nM). We speculated that increased FX levels could enhance coagulation potential in emicizumab-treated PwHA. AIMS: To investigate the relationship between FX concentrations and emicizumab-driven coagulation...

The emergence of SARS-CoV2 has presented itself as a significant global health crisis. The prevalence of thrombotic events is known to be high in these patients, affecting various organ systems, sometimes leading to cutaneous thrombosis, pulmonary embolism (PE), stroke, or coronary thrombosis. The available evidence suggests that thromboembolism, hypercoagulability, and the excessive production of proinflammatory cytokines play a significant role in the development of multiorgan failure. Methodology: This retrospective single-centre study was conducted at "Victor Babes" University of Medicine and Pharmacy from Timisoara, Romania, involving a total of 420 patients diagnosed with COVID-19...

BACKGROUND: Free labile hemin acts as a damage-associated molecular pattern during acute and chronic hemolysis and muscle injury supporting platelet activation and thrombosis. AIM: We investigated the anti-thrombotic potential of hydroxychloroquine on hemolysis-induced arterial thrombosis ex vivo, hemin-induced platelet activation, ferric-chloride (FeCl3 )-induced arterial thrombosis and lung perfusion following hemin injection in mice. RESULTS: Erythrocyte lysis and endothelial cell activation cooperatively supported platelet aggregation and thrombosis at arterial shear stress...

BACKGROUND AND PURPOSE: Hypolipidemia and platelet activation play key roles in atherosclerotic diseases. Pirinixic acid (WY-14643) was originally developed as a lipid-lowering drug. Here we focused on its antiplatelet and antithrombotic abilities and the underlying mechanism. EXPERIMENTAL APPROACH: The effects of WY-14643 on platelet aggregation was measured using a lumi-aggregometer. Clot retraction and spreading on fibrinogen were also assayed. PPARα-/- platelets were used to identify the target of WY-14643...

Marine natural products are important sources of novel drugs. In this study, we isolated 4-hydroxyphenylacetic acid (HPA) from the marine-derived fungus Emericellopsis maritima Y39-2. The antithrombotic activity and mechanism of HPA were reported for the first time. Using a zebrafish model, we found that HPA had a strong antithrombotic activity because it can significantly increase cardiac erythrocytes, blood flow velocity, and heart rate, reduce caudal thrombus, and reverse the inflammatory response caused by Arachidonic Acid (AA)...

Neuraminidases also called sialidases are glycosidases which catalyze the removal of terminal sialic acid residues from glycoproteins, glycolipids and oligosaccharides. Mammalian Neuraminidase-1 (NEU-1) participates in regulation of cell surface receptors such as insulin receptor (IR), epithelial growth factor receptor, low density lipoprotein receptor and toll like receptor 4. At the plasma membrane, NEU-1 can be associated with the elastin-binding protein and the carboxypeptidase protective protein/cathepsin A to constitute the elastin receptor complex...

Several studies in animal models and human cohorts have recently suggested that HDLs (high-density lipoproteins) not only modulate innate immune responses but also adaptative immune responses, particularly CD4+ T cells. CD4+ T cells are central effectors and regulators of the adaptive immune system, and any alterations in their homeostasis contribute to the pathogenesis of cardiovascular diseases, autoimmunity, and inflammatory diseases. In this review, we focus on how HDLs and their components affect CD4+ T-cell homeostasis by modulating cholesterol efflux, immune synapsis, proliferation, differentiation, oxidative stress, and apoptosis...

BACKGROUND: Low-dose aspirin is widely used for the secondary prevention of cardiovascular disease. The beneficial effects of low-dose aspirin are attributable to its inhibition of platelet Cox (cyclooxygenase)-1-derived thromboxane A2 . Until recently, the use of the Pf4 (platelet factor 4) Cre has been the only genetic approach to generating megakaryocyte/platelet ablation of Cox-1 in mice. However, Pf4-ΔCre displays ectopic expression outside the megakaryocyte/platelet lineage, especially during inflammation...

BACKGROUND: Myxomatous valve disease (MVD) is the most common cause of mitral regurgitation, leading to impaired cardiac function and heart failure. MVD in a mouse model of Marfan syndrome includes valve leaflet thickening and progressive valve degeneration. However, the underlying mechanisms by which the disease progresses remain undefined. METHODS: Mice with Fibrillin 1 gene variant Fbn1 C1039G/+ recapitulate histopathologic features of Marfan syndrome, and Wnt signaling activity was detected in TCF/Lef-lacZ reporter mice...

BACKGROUND: Heterogeneity in the severity of cerebral cavernous malformations (CCMs) disease, including brain bleedings and thrombosis that cause neurological disabilities in patients, suggests that environmental, genetic, or biological factors act as disease modifiers. Still, the underlying mechanisms are not entirely understood. Here, we report that mild hypoxia accelerates CCM disease by promoting angiogenesis, neuroinflammation, and vascular thrombosis in the brains of CCM mouse models...

BACKGROUND: Portal vein thrombosis (PVT), a complication of liver cirrhosis, is a major public health concern. PVT prediction is the most effective method for PVT diagnosis and treatment. AIM: To develop and validate a nomogram and network calculator based on clinical indicators to predict PVT in patients with cirrhosis. METHODS: Patients with cirrhosis hospitalized between January 2016 and December 2021 at the First Hospital of Lanzhou University were screened and 643 patients with cirrhosis who met the eligibility criteria were retrieved...

Recent studies have found a link between deep vein thrombosis and inflammatory reactions. N6-methyladenosine (m6A), a crucial element in immunological regulation, is believed to contribute to the pathophysiology of venous thromboembolism (VTE). However, how the m6A-modified immune microenvironment is involved in VTE remains unclear. In the present study, we identified a relationship between VTE and the expression of several m6A regulatory elements by analyzing peripheral blood samples from 177 patients with VTE and 88 healthy controls from public GEO databases GSE19151 and GSE48000...

Acute thrombosis secondary to atherosclerotic plaque rupture is the main cause of acute cardiac and cerebral ischemia. An animal model of unstable atherosclerotic plaques is highly important for investigating the mechanism of plaque rupture and thrombosis. However, current animal models involve complex operations, are costly, and have plaque morphologies that are different from those of humans. We aimed to establish a simple animal model of vulnerable plaques similar to those of humans. Rabbits were randomly divided into three groups...

OBJECTIVES: To assess and compare the Caprini and Padua risk assessment models (RAMs) for predicting venous thromboembolism (VTE) in hospitalized patients. METHODS: We retrospectively reviewed 28 VTE and 450 non-VTE patients hospitalized at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, in 2019. Their baseline medical, demographic, and radiological reports were recorded. We compared Caprini scores (defined at admission) and Padua scores (calculated retrospectively) for their ability to predict VTE...