Dual Inhibition of Factor XIIa and Factor XIa Produces a Synergistic Anticoagulant Effect.

Autor:	Jiang S; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China ; and., Li Y; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China ; and., Zhang J; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China ; and., Jia W; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China ; and., Zheng Y; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China ; and., Jia Z; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China ; and., Yu C; Department of Intervention Radiology, Lishui District People's Hospital, Nanjing, China ., Kong Y; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China ; and.
Jazyk:	angličtina
Zdroj:	Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 2024 Jul 01; Vol. 84 (1), pp. 71-80. Date of Electronic Publication: 2024 Jul 01.
DOI:	10.1097/FJC.0000000000001573
Abstrakt:	Abstract: Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk. Competing Interests: The authors report no conflicts of interest. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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