Vascular Endothelial Cells Produce Coagulation Factors That Control Their Growth via Joint Protease-Activated Receptor and C5a Receptor 1 (CD88) Signaling.

As per the classical view of the coagulation system, it functions solely in plasma to maintain hemostasis. An experimental approach modeling vascular reconstitution was used to show that vascular endothelial cells (ECs) endogenously synthesize coagulation factors during angiogenesis. Intracellular thrombin generated from this synthesis promotes the mitotic function of vascular endothelial cell growth factor A (VEGF-A). The thrombin concurrently cleaves C5a from EC-synthesized complement component C5 and unmasks the tethered ligand for EC-expressed protease-activated receptor 4 (PAR4). The two ligands jointly trigger EC C5a receptor-1 (C5ar1) and PAR4 signaling, which together promote VEGF receptor 2 growth signaling. C5ar1 is functionally associated with PAR4, enabling C5a or thrombin to elicit Gαi and/or Gαq signaling. EC coagulation factor and EC complement component synthesis concurrently down-regulate with contact inhibition. The connection of these processes with VEGF receptor 2 signaling provides new insights into mechanisms underlying angiogenesis. Knowledge of endogenous coagulation factor/complement component synthesis and joint PAR4/C5ar1 signaling could be applied to other cell types.

Embolic Shotgun Pellet to the Left Middle Cerebral Artery Causing Hemiplegia and Aphasia With Near Complete Clinical Recovery on Nonoperative Management.

A 28-year-old male presented after gunshot injury to his right side from a shotgun. He had no prior history of gunshot injury and no neurologic deficits on presentation. Initially, non-contrast computed tomography (CT) scans of the head, face, chest, abdomen, and pelvis demonstrated multiple pellets lodged in the patient's right upper extremity, face, abdomen, and right hemithorax which penetrated the right lung. A shotgun pellet was also found in the region of the left middle cerebral artery (MCA) on the head CT without contrast with no skull fracture or intracerebral hemorrhage. The patient subsequently developed right hemiplegia and expressive aphasia approximately 48 hours after the trauma. CT angiography (CTA) of the head and neck with perfusion at that time demonstrated ischemic penumbra and the location of the pellet to be in the distal left M1 branch. No intervention was performed given the location. The patient clinically improved without intervention. This is an uncommon injury and outcome for embolization of a foreign body.