Effects of histidine-rich glycoprotein on cerebral blood vessels

Delayed cerebral vasospasm is thought to be caused by factors released from a subarachnoid blood clot. Because vasospasm occurs several days after hemorrhage, we hypothesized that clotted blood releases vasoactive factors as it ages. Targeted proteomics identified histidine-rich glycoprotein (HRG) as a potentially vasoactive factor released within the first 72 hours of clot formation. In vitro studies revealed that HRG caused moderate (similar to 30%) dilation of cannulated cerebral arterioles and proliferation of cerebrovascular endothelial cells. We conclude that HRG released from clotted blood, while unlikely to contribute to cerebral vasospasm, might provide important vasodilatory or angiogenic stimuli after hemorrhagic stroke.