The resolution of arterial thrombi is critically dependent on the endogenous fibrinolytic system. Using well-established and complementary whole blood models, we investigated the endogenous fibrinolytic potential of the tissue-type plasminogen activator (tPA) and the intra-thrombus distribution of fibrinolytic proteins, formed ex vivo under shear. tPA was present at physiologically relevant concentrations and fibrinolysis was monitored using an FITC-labelled fibrinogen tracer. Thrombi were formed from anticoagulated blood using a Chandler Loop and from non-anticoagulated blood perfused over specially-prepared porcine aorta strips under low (212 s) and high shear (1690 s) conditions in a Badimon Chamber. Plasminogen, tPA and plasminogen activator inhibitor-1 (PAI-1) concentrations were measured by ELISA. The tPA-PAI-1 complex was abundant in Chandler model thrombi serum. In contrast, free tPA was evident in the head of thrombi and correlated with fibrinolytic activity. Badimon thrombi formed under high shear conditions were more resistant to fibrinolysis than those formed at low shear. Plasminogen and tPA concentrations were elevated in thrombi formed at low shear, while PAI-1 concentrations were augmented at high shear rates. In conclusion, tPA primarily localises to the thrombus head in a free and active form. Thrombi formed at high shear incorporate less tPA and plasminogen and increased PAI-1, thereby enhancing resistance to degradation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924342 | PMC |
| http://dx.doi.org/10.3390/ijms22042115 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Insights into Cancer-Associated Thrombosis Leading Towards Ischemic Stroke.
Biology (Basel)
January 2025
Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
Stroke leads to significant disability in most patients, whereas cancer elevates the occurrence of stroke. The incidence of cancer-associated stroke (CAS) is projected to rise as a result of improvements in cancer therapies. Various forms of cancer have been demonstrated to be linked to ischemic stroke.
View Article and Find Full Text PDFThe Link Between Venous and Arterial Thrombosis: Is There a Role for Endothelial Dysfunction?
Cells
January 2025
Department of Medical Biotechnologies and Translational Medicine, University of Milan, 20125 Milan, Italy.
Venous thromboembolism (VTE) and arterial thrombosis (AT) are distinct yet closely related pathological processes. While traditionally considered separate entities, accumulating evidence suggests that they share common risk factors, such as inflammation and endothelial dysfunction (ED). This review explores the parallels and differences between venous and arterial thrombosis, with particular attention to the role of unprovoked VTE and its potential links to atherosclerosis and systemic inflammation.
View Article and Find Full Text PDFIntraoperative Tranexamic Acid Infusion Reduces Perioperative Blood Loss in Pediatric Limb-Salvage Surgeries: A Double-Blinded Randomized Placebo-Controlled Trial.
J Bone Joint Surg Am
January 2025
National Cancer Institute, Cairo University, Giza, Egypt.
Background: Limb-salvage surgery for malignant bone tumors can be associated with considerable perioperative blood loss. The aim of this randomized controlled trial was to assess the safety and efficacy of the intraoperative infusion of tranexamic acid (TXA) in children and adolescents undergoing limb-salvage surgery.
Methods: All participants were <18 years of age at the time of surgery and diagnosed with a malignant bone tumor of the femur that was treated with resection and reconstruction with a megaprosthesis.
Annual epidemics of influenza result in 3-5 million cases of severe illness and more than 600 000 deaths. Severe forms of influenza are usually characterized by vascular endothelial cells damage. Thus, influenza A viruses, including subtypes A(H1N1)pdm09, A(H3N2), as well as highly pathogenic avian influenza viruses, can infect the vascular endothelium, leading to activation and subsequent dysfunction of these cells.
View Article and Find Full Text PDFAspirin Is as Effective and Safe as Oral Anticoagulants for Venous Thromboembolism Prophylaxis After Joint Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
J Bone Joint Surg Am
January 2025
Department of Orthopedics, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Taizhou, Zhejiang, People's Republic of China.
Background: Joint arthroplasty effectively treats osteoarthritis, providing pain relief and improving function, but postoperative venous thromboembolism (VTE) remains a common complication. This study therefore assessed the effectiveness and safety of aspirin compared with oral anticoagulants (OACs) for VTE prophylaxis after joint arthroplasty.
Methods: A systematic review and meta-analysis was performed by searching PubMed, Embase, the Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) up to May 14, 2024, that compared the effect of aspirin versus OACs on VTE prophylaxis in adults undergoing joint arthroplasty.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!