We have located links that may give you full text access.
MICROVASCULAR ENDOTHELIAL ACTIVATION/DYSFUNCTION AND DYSREGULATION OF THE ANGIOPOIETIN-TIE2 SYSTEM IN THE PATHOGENESIS OF LIFE-THREATENING INFECTIONS.
Microvascular endothelial activation/dysfunction has emerged as an important mechanistic pathophysiological process in the development of morbidity and mortality in life-threatening infections. The angiopoietin-Tie2 system plays an integral role in the regulation of microvascular endothelial integrity. Angiopoietin-1 (Ang-1), produced by platelets and pericytes, is the cognate agonistic ligand for Tie2, promoting endothelial quiescence and inhibiting microvascular leak. Angiopoietin-2 (Ang-2), released from activated endothelial cells in Weibel-Palade bodies, competes with Ang-1 for binding to Tie-2, thereby promoting endothelial activation/dysfunction and microvascular leak. In healthy homeostasis, levels of Ang-1 far exceed Ang-2 in circulating serum/plasma. In diseases associated with systemic inflammation, Ang-1 falls and Ang-2 rises (i.e., Ang-1/2 dysregulation). Our research has shown that Ang-1/2 dysregulation is a prominent feature in a number of life-threatening infections and critical illnesses, including sepsis, cerebral malaria, COVID-19, streptococcal toxic shock syndrome (STSS), hemolytic-uremic syndrome (HUS), dengue, and CAR T-cell-associated neurotoxicity. Further work has implicated Ang-1/2 dysregulation in the development of end-organ injury, including acute lung injury/ARDS, acute kidney injury (AKI), and blood-brain-barrier (BBB) breakdown. Current studies are focused in three areas: (a) translation of Ang-1 and -2 as clinically informative prognostic and "theranostic" biomarkers in critically ill individuals; (b) incorporation of Ang-1/2 assays in a point of care device for clinical triage decision making; and (c) development of an engineered Ang-1 super agonist nanoparticle as a novel pathogen-agnostic therapeutic to prevent and/or mitigate end-organ dysfunction in individuals with life-threatening infections and critical illnesses associated with systemic inflammation.
Full text links
Related Resources
Trending Papers
Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.International Journal of Molecular Sciences 2024 April 13
Executive Summary: State-of-the-Art Review: Unintended Consequences: Risk of Opportunistic Infections Associated with Long-term Glucocorticoid Therapies in Adults.Clinical Infectious Diseases 2024 April 11
Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.Epilepsia 2024 April 13
Finerenone: From the Mechanism of Action to Clinical Use in Kidney Disease.Pharmaceuticals 2024 March 27
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app