Ozanimod differentially preserves human cerebrovascular endothelial barrier proteins and attenuates matrix metalloproteinase-9 activity following in vitro acute ischemic injury
Trevor S. Wendt, Rayna J. Gonzales
Abstract
We have identified a potential novel mechanism by which ozanimod, a selective sphingosine-1-phosphate receptor 1 (S1PR1) agonist, attenuates hypoxia plus glucose deprivation (HGD)-induced matrix metalloproteinase-9 (MMP-9) activity and disruptions in integral human brain endothelial cell barrier proteins. Our results suggest that ischemic-like injury elicits increased MMP-9 activity and alterations of barrier integrity proteins in human brain microvascular endothelial cells (HBMECs) and that ozanimod via S1PR1 attenuates these HGD-induced responses, adding to its therapeutic potential in cerebrovascular protection during the acute phase of ischemic stroke.
Topics & Concepts
MedicineS1PR1Endothelial stem cellInternal medicineEndocrinologyBiologyVascular endothelial growth factor AVascular endothelial growth factorIn vitroBiochemistryVEGF receptorsBarrier Structure and Function StudiesAcute Ischemic Stroke ManagementProtease and Inhibitor Mechanisms