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The Metalloproteinase-Dependent Role Of Timps In Regulation Of Pulmonary Microvascular Endothelial Cell Barrier Function During Sepsis, Marcello G. Masciantonio

Electronic Thesis and Dissertation Repository

Sepsis causes injury and dysfunction of pulmonary microvascular endothelial cells (PMVEC), leading to pulmonary edema. Metalloproteinases, are associated with inflammation and tissue damage, and their regulation by tissue inhibitors of metalloproteinases (TIMPs) may protect against septic PMVEC dysfunction. Thus, I hypothesize that murine septic PMVEC barrier dysfunction is due to disruption of the balance between metalloproteinases and TIMPs leading to increased metalloproteinase activity.

PMVEC were isolated from wild type (WT) and Timp3^-/- mice. Timp and metalloproteinase mRNA expression was altered under septic conditions and this was associated with increased metalloproteinase activity. Global metalloproteinase inhibitors BB-94 and TAPI-2 reduced albumin …