Natalie DeGurse
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Natalie DeGurse has a total of 6 co-authors. Here are the top co-authors by number of shared publications:
- Cynthia Pape
Centre for Critical Illness Research, Lawson Health Research Institute, London, ON N6A 5W9, Canada
1 shared publication - Devika P. Jayawardena
Centre for Critical Illness Research, Lawson Health Research Institute, London, ON N6A 5W9, Canada
1 shared publication - Lefeng Wang
Centre for Critical Illness Research, Lawson Health Research Institute, London, ON N6A 5W9, Canada
1 shared publication - Marcello G. Masciantonio
Centre for Critical Illness Research, Lawson Health Research Institute, London, ON N6A 5W9, Canada
1 shared publication - Sanjay Mehta
Southwest Ontario PH Clinic, Department of Medicine, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada
1 shared publication - Sean E. Gill
Centre for Critical Illness Research, London Health Sciences Centre Research Institute, London, Ontario, Canada
1 shared publication
Latest Publications
- Open Access
- 26 April 2023
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 24 (9) , 7875
Imbalance of Pulmonary Microvascular Endothelial Cell-Expression of Metalloproteinases and Their Endogenous Inhibitors Promotes Septic Barrier Dysfunction
Sepsis is a life-threatening disease characterized by excessive inflammation leading to organ dysfunction. During sepsis, pulmonary microvascular endothelial cells (PMVEC) lose barrier function associated with inter-PMVEC junction disruption. Matrix metalloproteinases (MMP) and a disintegrin and metalloproteinases (ADAM), which are regulated by tissue inhibitors of metalloproteinases (TIMPs), can cleave cell–cell junctional proteins, suggesting a role in PMVEC barrier dysfunction. We hypothesize that septic PMVEC barrier dysfunction is due to a disruption in the balance between PMVEC-specific metalloproteinases and TIMPs leading to increased metalloproteinase activity. The effects of sepsis on TIMPs and metalloproteinases were assessed ex vivo in PMVEC from healthy (sham) and septic (cecal ligation and perforation) mice, as well as in vitro in isolated PMVEC stimulated with cytomix, lipopolysaccharide (LPS), and cytomix + LPS vs. PBS. PMVEC had high basal Timp expression and lower metalloproteinase expression, and septic stimulation shifted expression in favour of metalloproteinases. Septic stimulation increased MMP13 and ADAM17 activity associated with a loss of inter-PMVEC junctional proteins and barrier dysfunction, which was rescued by treatment with metalloproteinase inhibitors. Collectively, our studies support a role for metalloproteinase–TIMP imbalance in septic PMVEC barrier dysfunction, and suggest that inhibition of specific metalloproteinases may be a therapeutic avenue for septic patients.
- 26 April 2023
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 24 (9) , 7875
Open AccessImbalance of Pulmonary Microvascular Endothelial Cell-Expression of Metalloproteinases and Their Endogenous Inhibitors Promotes Septic Barrier Dysfunction
Sepsis is a life-threatening disease characterized by excessive inflammation leading to organ dysfunction. During sepsis, pulmonary microvascular endothelial cells (PMVEC) lose barrier function associated with inter-PMVEC junction disruption. Matrix metalloproteinases (MMP) and a disintegrin and metalloproteinases (ADAM), which are regulated by tissue inhibitors of metalloproteinases (TIMPs), can cleave cell–cell junctional proteins, suggesting a role in PMVEC barrier dysfunction. We hypothesize that septic PMVEC barrier dysfunction is due to a disruption in the balance between PMVEC-specific metalloproteinases and TIMPs leading to increased metalloproteinase activity. The effects of sepsis on TIMPs and metalloproteinases were assessed ex vivo in PMVEC from healthy (sham) and septic (cecal ligation and perforation) mice, as well as in vitro in isolated PMVEC stimulated with cytomix, lipopolysaccharide (LPS), and cytomix + LPS vs. PBS. PMVEC had high basal Timp expression and lower metalloproteinase expression, and septic stimulation shifted expression in favour of metalloproteinases. Septic stimulation increased MMP13 and ADAM17 activity associated with a loss of inter-PMVEC junctional proteins and barrier dysfunction, which was rescued by treatment with metalloproteinase inhibitors. Collectively, our studies support a role for metalloproteinase–TIMP imbalance in septic PMVEC barrier dysfunction, and suggest that inhibition of specific metalloproteinases may be a therapeutic avenue for septic patients.