ResearchIn-Press PreviewVascular biology
Open Access | 10.1172/jci.insight.155010
1Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Surgery, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
4Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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Richter, R.
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1Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Surgery, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
4Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Surgery, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
4Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Surgery, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
4Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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Pretorius, D.
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1Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Surgery, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
4Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Surgery, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
4Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Surgery, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
4Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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1Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America
2Department of Surgery, University of Alabama at Birmingham, Birmingham, United States of America
3Department of Pathology, University of Alabama at Birmingham, Birmingham, United States of America
4Department of Medicine, University of Alabama at Birmingham, Birmingham, United States of America
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Published June 28, 2022 - More info
Angiopoietin-2 (Ang-2) is a key mediator of vascular disease during sepsis, and elevated plasma levels of Ang-2 are associated with organ injury scores and poor clinical outcomes. We have previously observed that biomarkers of endothelial glycocalyx (EG) damage correlate with plasma Ang-2 levels, suggesting a potential mechanistic linkage between EG injury and Ang-2 expression during states of systemic inflammation. However, the cell signaling mechanisms regulating Ang-2 expression following EG damage are unknown. In the current study, we determined the temporal associations between plasma heparan sulfate (HS) levels as a marker of EG erosion and plasma Ang-2 levels in children with sepsis and in mouse models of sepsis. Secondly, we evaluated the role of shear stress-mediated 5’-adenosine monophosphate-activated protein kinase (AMPK) signaling in Ang-2 expression following enzymatic HS cleavage from the surface of human primary lung microvascular endothelial cells (HLMVEC). We found that plasma HS levels peak prior to plasma Ang-2 levels in children and mice with sepsis. Further, we discovered that impaired AMPK signaling contributes to increased Ang-2 expression following HS cleavage from flow conditioned HLMVECs, establishing a novel paradigm by which Ang-2 may be upregulated during sepsis.