Cerebral cavernous malformations form an anticoagulant vascular domain in humans and mice.

ABSTRACT: Cerebral cavernous malformations (CCMs) are common brain vascular dysplasias that are prone to acute and chronic hemorrhage with significant clinical sequelae. The pathogenesis of recurrent bleeding in CCM is incompletely understood. Here, we show that central nervous system hemorrhage in CCMs is associated with locally elevated expression of the anticoagulant endothelial receptors thrombomodulin (TM) and endothelial protein C receptor (EPCR). TM levels are increased in human CCM lesions, as well as in the plasma of patients with CCMs. In mice, endothelial-specific genetic inactivation of Krit1 (Krit1 ^ECKO ) or Pdcd10 (Pdcd10 ^ECKO ), which cause CCM formation, results in increased levels of vascular TM and EPCR, as well as in

SUBMITTER: Lopez-Ramirez MA 

PROVIDER: S-EPMC6337879 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature