NDLI: Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis

Content Provider	Springer Nature : BioMed Central
Author	Alfieri, Alessio Watson, Jay J Kammerer, Richard A Tasab, Mohammed Progias, Pavlos Reeves, Kimberly Brown, Nicola J Brookes, Zoe L
Abstract	Introduction Severe sepsis is characterised by intravascular or extravascular infection with microbial agents, systemic inflammation and microcirculatory dysfunction, leading to tissue damage, organ failure and death. The growth factor angiopoietin (Ang-1) has therapeutic potential but recombinant Ang-1 tends to aggregate and has a short half-life in vivo. This study aimed to investigate the acute effects of the more stable Ang-1 variant matrilin-1-angiopoietin-1 (MAT.Ang-1) on the function of the microcirculation in an experimental model of sepsis, and whether any protection by MAT-Ang-1 was associated with modulation of inflammatory cytokines, angiogenic factors or the endothelial nitric oxide synthase (eNOS)-Akt and vascular endothelial (VE)-cadherin pathways. Methods Aluminium window chambers were implanted into the dorsal skinfold of male C3H/HeN mice (7 to 10 weeks old) to expose the striated muscle microcirculation. Endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (LPS, 1 mg/kg at 0 and 19 hours). MAT.Ang-1 was administered intravenously 20 hours after the onset of sepsis. Microcirculatory function was evaluated by intravital microscopy and Doppler fluximetry. Results Endotoxemia resulted in macromolecular leak, which was ameliorated by MAT.Ang-1 post-treatment. LPS induced a dramatic reduction in tissue perfusion, which was improved by MAT.Ang-1. Proteome profiler array analysis of skeletal muscle also demonstrated increased inflammatory and reduced angiogenic factors during endotoxemia. MAT.Ang-1 post-treatment reduced the level of IL-1β but did not significantly induce the expression of angiogenic factors. MAT.Ang-1 alone did not induce leak or increase angiogenic factors but did reduce vascular endothelial growth factor expression in controls. Conclusion Administration of MAT.Ang-1 after the onset of sepsis protects the microcirculation from endotoxemia-induced vascular dysfunction through reducing inflammation but without pro-angiogenic actions, thus representing a novel, potential pharmacotherapeutic agent for the treatment of sepsis.
Related Links	https://ccforum.biomedcentral.com/counter/pdf/10.1186/cc11666.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	13648535
DOI	10.1186/cc11666
Journal	Critical Care
Issue Number	5
Volume Number	16
Language	English
Publisher	BioMed Central
Publisher Date	2012-10-04
Access Restriction	Open
Subject Keyword	Intensive Critical Care Medicine Emergency Medicine Vascular Endothelial Growth Factor Angiogenic Factor Microvascular Permeability Microvascular Blood Flow Window Chamber
Content Type	Text
Resource Type	Article
Subject	Critical Care and Intensive Care Medicine
Journal Impact Factor	8.8/2023
5-Year Journal Impact Factor	10.4/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis

RESEARCH Open Access Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis

Role of TREM-1 in endothelial dysfunction during experimental sepsis

Does low angiopoietin-1 predict adverse outcome in sepsis?

Interplay between angiopoietin-2, vascular endothelial growth factor and peroxynitrite is an important determinant of vascular hyperpermeability during methicillin-resistant Staphylococcus aureus sepsis

Angiopoietin-2 is increased in sepsis and inversely associated with nitric oxide-dependent microvascular reactivity

Microvascular dysfunction as a cause of organ dysfunction in severe sepsis

Angiogenic factors in sepsis: are we ready for the new therapeutic era?

Pulmonary vascular permeability changes in an ovine model of methicillin-resistant Staphylococcus aureus sepsis

Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis

Similar Documents

Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis

RESEARCH Open Access Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis

Role of TREM-1 in endothelial dysfunction during experimental sepsis

Does low angiopoietin-1 predict adverse outcome in sepsis?

Interplay between angiopoietin-2, vascular endothelial growth factor and peroxynitrite is an important determinant of vascular hyperpermeability during methicillin-resistant Staphylococcus aureus sepsis

Angiopoietin-2 is increased in sepsis and inversely associated with nitric oxide-dependent microvascular reactivity

Microvascular dysfunction as a cause of organ dysfunction in severe sepsis

Angiogenic factors in sepsis: are we ready for the new therapeutic era?

Pulmonary vascular permeability changes in an ovine model of methicillin-resistant Staphylococcus aureus sepsis

Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis