The evolution of factor XI and the kallikrein-kinin system
| Autor: | Andras Gruber, Mao Fu Sun, Christian J. Kastrup, Priyanka Srivastava, Jonas Emsley, S. Kent Dickeson, David Gailani, Alec LaPlace, Aleksandr Shamanaev, Michal B. Ponczek |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Factor XIIa Factor XI Deficiency Kallikrein-Kinin System 030204 cardiovascular system & hematology Biology Thrombosis and Hemostasis 03 medical and health sciences 0302 clinical medicine Thrombin Pregnancy Zymogen medicine Animals Humans Factor XI Factor IX Kininogen Prekallikrein Hematology Cell biology 030104 developmental biology Coagulation Hemostasis Female medicine.drug circulatory and respiratory physiology |
| Zdroj: | Blood Adv |
| ISSN: | 2473-9537 |
| Popis: | Factor XI (FXI) is the zymogen of a plasma protease (FXIa) that contributes to hemostasis by activating factor IX (FIX). In the original cascade model of coagulation, FXI is converted to FXIa by factor XIIa (FXIIa), a component, along with prekallikrein and high-molecular-weight kininogen (HK), of the plasma kallikrein-kinin system (KKS). More recent coagulation models emphasize thrombin as a FXI activator, bypassing the need for FXIIa and the KKS. We took an evolutionary approach to better understand the relationship of FXI to the KKS and thrombin generation. BLAST searches were conducted for FXI, FXII, prekallikrein, and HK using genomes for multiple vertebrate species. The analysis shows the KKS appeared in lobe-finned fish, the ancestors of all land vertebrates. FXI arose later from a duplication of the prekallikrein gene early in mammalian evolution. Features of FXI that facilitate efficient FIX activation are present in all living mammals, including primitive egg-laying monotremes, and may represent enhancement of FIX-activating activity inherent in prekallikrein. FXI activation by thrombin is a more recent acquisition, appearing in placental mammals. These findings suggest FXI activation by FXIIa may be more important to hemostasis in primitive mammals than in placental mammals. FXI activation by thrombin places FXI partially under control of the vitamin K-dependent coagulation mechanism, reducing the importance of the KKS in blood coagulation. This would explain why humans with FXI deficiency have a bleeding abnormality, whereas those lacking components of the KKS do not. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|