Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations.

ABSTRACT:

Purpose

The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established.

Methods

We analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations.

Results

We determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and pe

SUBMITTER: Shenkar R 

PROVIDER: S-EPMC4329119 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature