2014
DOI: 10.1074/jbc.m114.569665
|View full text |Cite
|
Sign up to set email alerts
|

Platelets Contain Tissue Factor Pathway Inhibitor-2 Derived from Megakaryocytes and Inhibits Fibrinolysis

Abstract: Background: TFPI-2 inhibits plasma kallikrein, FXIa, and plasmin, but its concentration in normal plasma is insufficient to inhibit clotting or fibrinolysis. Results: Platelets contain TFPI-2 derived from megakaryocytes and binds to platelet FV/Va and circulating FV in late pregnancy when plasma TFPI-2 is ϳ7 nM. Conclusion: Platelet-derived TFPI-2 regulates intrinsic coagulation and tPA-induced fibrinolysis. Significance: Platelet-derived TFPI-2 promotes clot stabilization while attenuating intrinsic clotting.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

0
37
0

Year Published

2017
2017
2024
2024

Publication Types

Select...
7
1

Relationship

0
8

Authors

Journals

citations
Cited by 21 publications
(37 citation statements)
references
References 78 publications
0
37
0
Order By: Relevance
“…This suggests that TFPI initially engages the FXIa active site through its Kunitz domains. The TFPI homolog TFPI-2 inhibits FXIa and kallikrein via its first Kunitz domain [174,175]. Desmolaris is a homolog of TFPI lacking the Kunitz-1 domain that is expressed in the salivary gland of the vampire bat Desmodus rotundus [176].…”
Section: Therapeutic Targeting Of Contact Factorsmentioning
confidence: 99%
“…This suggests that TFPI initially engages the FXIa active site through its Kunitz domains. The TFPI homolog TFPI-2 inhibits FXIa and kallikrein via its first Kunitz domain [174,175]. Desmolaris is a homolog of TFPI lacking the Kunitz-1 domain that is expressed in the salivary gland of the vampire bat Desmodus rotundus [176].…”
Section: Therapeutic Targeting Of Contact Factorsmentioning
confidence: 99%
“…This is different from other inhibitory proteins that contain multiple Kunitz-type domains, where the Kunitz-type domains are linked sequentially and at least one of its Kunitz domains is not interrupted by other domains. Examples of these multi-Kunitz-type domain proteins include 1) tissue factor pathway inhibitor with three Kunitz domains, and the Kunitz domains in the inhibitors are not interrupted by another domain (7,38); 2) bikunin, com-posed of two Kunitz-type domains packed close together with the protease binding site in Kunitz domain 1 exposing to solution, but the protease binding site in the Kunitz domain 2 impeded by Kunitz domain 1 (39); and 3) HAI-2, an inhibitor with high homology to HAI-1 but contained only Kunitz domain 1 and Kunitz domain 2, was reported to inhibit HGFA with Kunitz domain 1 as the functional domain in human, but in mouse the truncated HAI-2 contained only Kunitz domain 2 was also an efficient HGFA inhibitor. Whether the discrepancy results from different domain arrangement of these two Kunitz domains in human and mouse is still unknown (40 -43).…”
Section: A New Mode Of Kunitz Domain Association In a Multi-kunitz Domentioning
confidence: 99%
“…TFPI-2, a homologue of TFPI-1, has recently been identified within platelets and is of megakaryocytic origin. 113 TFPI-2 is released from platelets in response to TRAP-6 stimulation and strongly attenuates tPA-mediated plasma clot lysis by directly inhibiting plasmin. The levels of TFPI-2 rise steadily during pregnancy potentially, indicating an antifibrinolytic role for this Kunitz inhibitor in control of bleeding during labor.…”
Section: Tissue Factor Pathway Inhibitormentioning
confidence: 99%
“…The levels of TFPI-2 rise steadily during pregnancy potentially, indicating an antifibrinolytic role for this Kunitz inhibitor in control of bleeding during labor. 113…”
Section: Tissue Factor Pathway Inhibitormentioning
confidence: 99%