Thrombin in complex with dabigatran can still interact with PAR-1 via exosite-I and instigate loss of vascular integrity.

ABSTRACT:

Background

Atrial fibrillation (AF) can lead to the loss of microvascular integrity thereby enhancing AF progression. Mechanistically, the pro-coagulant state that drives the risk of stroke in patients with AF may also play a causal role in microvascular loss. Direct oral anticoagulants (DOACs), the preferred anticoagulants for AF, can target factors upstream (factor Xa [FXa]) or downstream (thrombin) in the coagulation cascade and mediate differential vascular effects through interaction with protease-activated receptors (PARs).

Objective

To investigate the potential effect of different DOACs on vascular integrity.

Methods

To model the impact of DOACs on vascular integrity, we utilized platelet-free plasma in thrombin generation assays and endothelial barrier assays

SUBMITTER: Dolleman SC 

PROVIDER: S-EPMC9306515 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature