SUR1-TRPM4 channel activation and phasic secretion of MMP-9 induced by tPA in brain endothelial cells.

ABSTRACT:

Background

Hemorrhagic transformation is a major complication of ischemic stroke, is linked to matrix metalloproteinase-9 (MMP-9), and is exacerbated by tissue plasminogen activator (tPA). Cerebral ischemia/reperfusion is characterized by SUR1-TRPM4 (sulfonylurea receptor 1-transient receptor potential melastatin 4) channel upregulation in microvascular endothelium. In humans and rodents with cerebral ischemia/reperfusion (I/R), the SUR1 antagonist, glibenclamide, reduces hemorrhagic transformation and plasma MMP-9, but the mechanism is unknown. We hypothesized that tPA induces protease activated receptor 1 (PAR1)-mediated, Ca2+-dependent phasic secretion of MMP-9 from activated brain endothelium, and that SUR1-TRPM4 is required for this process.

Methods

Cerebral I/R, of 2 a

SUBMITTER: Gerzanich V 

PROVIDER: S-EPMC5884564 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature