ArticleCardiovascular drugs and therapy2021
Apixaban Downregulates Endothelial Inflammatory and Prothrombotic Phenotype in an In Vitro Model of Endothelial Dysfunction in Uremia.
Article in Cardiovascular drugs and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- The Impact of NOACS versus VKAS on Absolute and Relative Cognitive Function Decline Over Time: A Machine Learning Approach.Thrombosis and haemostasis · 2026Observational
- Common Biomarkers of Endothelial Dysfunction Across Highly Prevalent Diseases with Cardiovascular Risk: Functional Characterization and Prognostic Implications.International journal of molecular sciences · 2026Article
- Anticoagulants beyond coagulation: a narrative review of cardiovascular effects.Cardiovascular research · 2026Review
- Antiphospholipid Antibody Persistent Positivity Is Associated with Worsened Endothelial Dysfunction in Hemodialysis Patients: A Cross-Sectional Study.Journal of clinical medicine · 2025Article
- Article
- Mitochondrial Dysfunction in Atrial Fibrillation: The Need for a Strong Pharmacological Approach.Biomedicines · 2024Review
- Beyond Anticoagulation: A Comprehensive Review of Non-Vitamin K Oral Anticoagulants (NOACs) in Inflammation and Protease-Activated Receptor Signaling.International journal of molecular sciences · 2024Review
- Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings.Biomolecules · 2024Review
- Pleiotropic Effects of Direct Oral Anticoagulants in Chronic Heart Failure and Atrial Fibrillation: Machine Learning Analysis.Molecules (Basel, Switzerland) · 2024Article
- Relationship of Warfarin and Apixaban with Vascular Function in Patients with Atrial Fibrillation.Journal of vascular research · 2024Article
- Ferroptosis of Endothelial Cells Triggered by Erythrophagocytosis Contributes to Thrombogenesis in Uremia.Thrombosis and haemostasis · 2023Article
- Anti-Inflammatory and Anticancer Effects of Anticoagulant Therapy in Patients with Malignancy.Life (Basel, Switzerland) · 2023Review
- Antioxidant Properties of Oral Antithrombotic Therapies in Atherosclerotic Disease and Atrial Fibrillation.Antioxidants (Basel, Switzerland) · 2023Review
- Direct Oral Anticoagulants for Stroke and Systemic Embolism Prevention in Patients with Left Ventricular Thrombus.Journal of personalized medicine · 2023Review
- Distinct pleiotropic effects of direct oral anticoagulants on cultured endothelial cells: a comprehensive review.Frontiers in pharmacology · 2023Review
- Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed.International journal of molecular sciences · 2022Review
- Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications?Cardiovascular drugs and therapy · 2022Review
- Rivaroxaban improves vascular response in LPS-induced acute inflammation in experimental models.PloS one · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeChronic kidney disease (CKD) associates with inflammatory and prothrombotic phenotypes, resulting in higher cardiovascular risk. Factor Xa displays functions beyond coagulation, exhibiting proinflammatory effects. The aim of the present study was to investigate whether a direct FXa inhibitor protects from the endothelial dysfunction (ED) caused by uremia.
methodsMacro (HUVEC) and microvascular (HMEC) endothelial cells (ECs) were exposed to serum from uremic patients or healthy donors, in absence and presence of apixaban (60 ng/ml). We evaluated changes in surface VCAM-1 and ICAM-1, intracellular eNOS, reactive oxygen species (ROS), and von Willebrand Factor (VWF) production by immunofluorescence, reactivity of the extracellular matrix (ECM) towards platelets, and intracellular signaling.
resultsECs exposed to uremic serum triggered dysregulation of all the parameters. Presence of apixaban resulted in decreased expression of VCAM-1 (178 ± 14 to 89 ± 2% on HMEC and 324 ± 71 to 142 ± 25% on HUVEC) and ICAM-1 (388 ± 60 to 111 ± 10% on HMEC and 148 ± 9% to 90 ± 7% on HUVEC); increased eNOS (72 ± 8% to 95 ± 10% on HMEC); normalization of ROS levels (173 ± 21 to 114 ± 13% on HMEC and 165 ± 14 to 127 ± 7% on HUVEC); lower production of VWF (168 ± 14 to 92 ± 4% on HMEC and 151 ± 22 to 99 ± 11% on HUVEC); and decreased platelet adhesion onto ECM (134 ± 22 to 93 ± 23% on HMEC and 161 ± 14 to 117 ± 7% on HUVEC). Apixaban inhibited p38MAPK and p42/44 activation in HUVEC (139 ± 15 to 48 ± 15% and 411 ± 66 to 177 ± 57%, respectively) (p < 0.05 vs control for all parameters).
conclusionAnti-FXa strategies, such as apixaban, prevented ED caused by the uremic milieu, exhibiting anti-inflammatory and antioxidant properties and modulating the reactivity of the ECM.
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