Related Experiment Videos
Dabigatran abrogates brain endothelial cell permeability in response to thrombin
Brian Thomas Hawkins1, Yu-Huan Gu1, Yoshikane Izawa1
1Department of Medicine (Hematology), Division of Hematology, Seattle, Washington, USA.
Summary
Dabigatran, an antithrombin, protects the brain's microvessel barrier from thrombin-induced permeability increases. This mechanism may reduce intracerebral hemorrhage risk in atrial fibrillation (AF) patients experiencing ischemic stroke.
Area of Science:
- Neuroscience
- Pharmacology
- Vascular Biology
Background:
- Atrial fibrillation (AF) elevates stroke risk, and antithrombotic treatments can increase bleeding complications.
- Thrombin plays a role in cerebral ischemia-induced microvessel injury.
- Dabigatran has shown efficacy in reducing thromboembolism and intracerebral hemorrhage compared to warfarin.
Purpose of the Study:
- To investigate if dabigatran reduces intracerebral hemorrhage risk by inhibiting thrombin-mediated increases in cerebral endothelial cell permeability.
- To explore dabigatran's direct effect on the brain's microvessel barrier.
Main Methods:
- Primary murine brain endothelial cells (mBECs) were treated with thrombin and dabigatran.
- Endothelial cell permeability was measured using fluorescein isothiocyanate-dextran.
- Effects of oxygen-glucose deprivation (OGD) and thrombin on permeability were assessed with and without dabigatran.
Main Results:
- Thrombin increased endothelial cell permeability concentration-dependently without causing cell death.
- Dabigatran completely blocked thrombin-induced permeability increases.
- Dabigatran also abrogated permeability increases caused by OGD and the combined effect of OGD and thrombin.
Conclusions:
- Dabigatran protects the microvessel permeability barrier against thrombin challenge.
- This protective effect on endothelial cells may explain dabigatran's reduced risk of intracerebral hemorrhage in AF-related ischemia.
Related Concept Videos
01:29Venous Thrombosis III: Interprofessional Care
265
Venous thrombosis requires effective prevention and treatment strategies to improve patient outcomes and reduce potential complications.Prevention StrategiesHealthcare providers must prioritize preventing venous thromboembolism (VTE) for all adult patients upon admission. Interventions depend on bleeding and thrombosis risk, medical history, current medications, diagnoses, planned procedures, and patient preferences. Patients on bed rest should change positions every two hours and, if not...
265
01:30Venous Thrombosis I: Introduction
310
Venous thrombosis, the most common disorder of the veins, involves the formation of a thrombus or blood clot associated with vein inflammation. It can be classified as either superficial vein thrombosis or deep vein thrombosis.Superficial Vein Thrombosis: This involves the formation of a thrombus in a superficial vein, usually the greater or lesser saphenous vein. Though less severe than deep vein thrombosis (DVT), SVT can lead to complications if untreated.Deep Vein Thrombosis (DVT): This...
310
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
2.0K
Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
2.0K
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
1.6K
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
1.6K
01:16Clot Retraction and Fibrinolysis
8.3K
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
8.3K
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
1.0K
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
1.0K