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Endogenous fibrinolysis facilitates clot retraction in vivo
- Source :
- Blood. 130(23)
- Publication Year :
- 2017
-
Abstract
- Clot retraction refers to the process whereby activated platelets transduce contractile forces onto the fibrin network of a thrombus, which over time increases clot density and decreases clot size. This process is considered important for promoting clot stability and maintaining blood vessel patency. Insights into the mechanisms regulating clot retraction at sites of vascular injury have been hampered by a paucity of in vivo experimental models. By pairing localized vascular injury with thrombin microinjection in the mesenteric circulation of mice, we have demonstrated that the fibrin network of thrombi progressively compacts over a 2-hour period. This was a genuine retraction process, as treating thrombi with blebbistatin to inhibit myosin IIa-mediated platelet contractility prevented shrinkage of the fibrin network. Real-time confocal analysis of fibrinolysis after recombinant tissue-type plasminogen activator (tPA) administration revealed that incomplete proteolysis of fibrin polymers markedly facilitated clot retraction. Similarly, inhibiting endogenous fibrinolysis with tranexamic acid reduced retraction of fibrin polymers in vivo. In vitro clot retraction experiments indicated that subthreshold doses of tPA facilitated clot retraction through a plasmin-dependent mechanism. These effects correlated with changes in the elastic modulus of fibrin clots. These findings define the endogenous fibrinolytic system as an important regulator of clot retraction, and show that promoting clot retraction is a novel and complementary means by which fibrinolytic enzymes can reduce thrombus size.
- Subjects :
- 0301 basic medicine
Blood Platelets
Male
medicine.medical_specialty
Plasmin
medicine.medical_treatment
Immunology
Clot Retraction
macromolecular substances
Clot retraction
030204 cardiovascular system & hematology
Biochemistry
Fibrin
03 medical and health sciences
Mice
0302 clinical medicine
Thrombin
Fibrinolysis
medicine
Animals
Humans
Platelet activation
Thrombus
biology
Chemistry
Nonmuscle Myosin Type IIA
digestive, oral, and skin physiology
Thrombosis
Cell Biology
Hematology
Actomyosin
medicine.disease
Surgery
030104 developmental biology
Tranexamic Acid
Tissue Plasminogen Activator
Biophysics
biology.protein
Plasminogen activator
circulatory and respiratory physiology
medicine.drug
Subjects
Details
- ISSN :
- 15280020
- Volume :
- 130
- Issue :
- 23
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....af2780439462bafae3bd91e5fd32d9d3