Cardiolipin-mediated procoagulant activity of mitochondria contributes to traumatic brain injury-associated coagulopathy in mice.
Blood
; 127(22): 2763-72, 2016 06 02.
Article
en En
| MEDLINE
| ID: mdl-27002118
ABSTRACT
Cardiolipin (CL) is an anionic phospholipid located exclusively in the mitochondrial inner membrane. Its presence in blood indicates mitochondrial damage and release from injured cells. Here, we report the detection of CL-exposed brain-derived mitochondrial microparticles (mtMPs) at 17 547 ± 2677/µL in the peripheral blood of mice subjected to fluid percussion injury to the brain. These mtMPs accounted for 55.2% ± 12.6% of all plasma annexin V-binding microparticles found in the acute phase of injury. They were also released from cultured neuronal and glial cells undergoing apoptosis. The mtMPs synergized with platelets to facilitate vascular leakage by disrupting the endothelial barrier. The disrupted endothelial barrier allowed the release of mtMPs into the systemic circulation to promote coagulation in both traumatically injured and mtMP- or CL-injected mice, leading to enhanced fibrinolysis, vascular fibrin deposition, and thrombosis. This mtMP-induced coagulation was mediated by CL transported from the inner to the outer mitochondrial membrane and was blocked by the scavenging molecule lactadherin. The mtMP-bound CL was â¼1600 times as active as purified CL in promoting coagulation. This study uncovered a novel procoagulant activity of CL and CL-exposed mitochondria that may contribute to traumatic brain injury-associated coagulopathy and identified potential pathways to block this activity.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trastornos de la Coagulación Sanguínea
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Cardiolipinas
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Membranas Mitocondriales
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Micropartículas Derivadas de Células
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Lesiones Traumáticas del Encéfalo
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Mitocondrias
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Blood
Año:
2016
Tipo del documento:
Article