Metabolic Response in Endothelial Cells to Catecholamine Stimulation Associated with Increased Vascular Permeability

Disruption to endothelial cell homeostasis results in an extensive variety of human pathologies that are particularly relevant to major trauma. Circulating catecholamines, such as adrenaline and noradrenaline, activate endothelial adrenergic receptors triggering a potent response in endothelial func...

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Bibliographic Details
Published in:	International journal of molecular sciences Vol. 23; no. 6; p. 3162
Main Authors:	López García de Lomana, Adrián, Vilhjálmsson, Arnar Ingi, McGarrity, Sarah, Sigurðardóttir, Rósa, Anuforo, Ósk, Viktorsdóttir, Alexía Rós, Kotronoulas, Aris, Bergmann, Andreas, Franzson, Leifur, Halldórsson, Haraldur, Henriksen, Hanne H, Wade, Charles E, Johansson, Pär Ingemar, Rolfsson, Óttar
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 15-03-2022 MDPI
Subjects:	Adrenergic receptors Aerobic respiration Angiogenesis Ascorbic acid Biomarkers Biosynthesis Blood vessels Capillary Permeability Catecholamine Catecholamines Catecholamines - metabolism Cell culture Endothelial cells Endothelial Cells - metabolism endotheliopathy Endothelium Endothelium, Vascular - metabolism Epinephrine Epinephrine - metabolism Epinephrine - pharmacology Feedback loops Glucose Homeostasis Humans major trauma Metabolic pathways Metabolic response Metabolism Metabolites metabolomics Nitric oxide Nitric Oxide - metabolism Noradrenaline Norepinephrine Norepinephrine - metabolism Norepinephrine - pharmacology Oxidative stress Permeability Receptor mechanisms Receptors (physiology) Respiration Stimulation Trauma Tumor necrosis factor-TNF vascular permeability catecholamines vascular permeability metabolomics major trauma endotheliopathy
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Summary:	Disruption to endothelial cell homeostasis results in an extensive variety of human pathologies that are particularly relevant to major trauma. Circulating catecholamines, such as adrenaline and noradrenaline, activate endothelial adrenergic receptors triggering a potent response in endothelial function. The regulation of the endothelial cell metabolism is distinct and profoundly important to endothelium homeostasis. However, a precise catalogue of the metabolic alterations caused by sustained high catecholamine levels that results in endothelial dysfunction is still underexplored. Here, we uncover a set of up to 46 metabolites that exhibit a dose-response relationship to adrenaline-noradrenaline equimolar treatment. The identified metabolites align with the glutathione-ascorbate cycle and the nitric oxide biosynthesis pathway. Certain key metabolites, such as arginine and reduced glutathione, displayed a differential response to treatment in early (4 h) compared to late (24 h) stages of sustained stimulation, indicative of homeostatic metabolic feedback loops. Furthermore, we quantified an increase in the glucose consumption and aerobic respiration in endothelial cells upon catecholamine stimulation. Our results indicate that oxidative stress and nitric oxide metabolic pathways are downstream consequences of endothelial cell stimulation with sustained high levels of catecholamines. A precise understanding of the metabolic response in endothelial cells to pathological levels of catecholamines will facilitate the identification of more efficient clinical interventions in trauma patients.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms23063162