Metabolic Response in Endothelial Cells to Catecholamine Stimulation Associated with Increased Vascular Permeability
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Metabolic Response in Endothelial Cells to Catecholamine Stimulation Associated with Increased Vascular Permeability. / 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.
In: International Journal of Molecular Sciences, Vol. 23, No. 6, 3162, 2022, p. 1-18.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Metabolic Response in Endothelial Cells to Catecholamine Stimulation Associated with Increased Vascular Permeability
AU - López García de Lomana, Adrián
AU - Vilhjálmsson, Arnar Ingi
AU - McGarrity, Sarah
AU - Sigurðardóttir, Rósa
AU - Anuforo, Ósk
AU - Viktorsdóttir, Alexía Rós
AU - Kotronoulas, Aris
AU - Bergmann, Andreas
AU - Franzson, Leifur
AU - Halldórsson, Haraldur
AU - Henriksen, Hanne H.
AU - Wade, Charles E.
AU - Johansson, Pär Ingemar
AU - Rolfsson, Óttar
N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022
Y1 - 2022
N2 - 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 under-explored. 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.
AB - 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 under-explored. 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.
KW - Catecholamines
KW - Endotheliopathy
KW - Major trauma
KW - Metabolomics
KW - Vascular permeability
UR - http://www.scopus.com/inward/record.url?scp=85126386403&partnerID=8YFLogxK
U2 - 10.3390/ijms23063162
DO - 10.3390/ijms23063162
M3 - Journal article
C2 - 35328583
AN - SCOPUS:85126386403
VL - 23
SP - 1
EP - 18
JO - International Journal of Molecular Sciences (Online)
JF - International Journal of Molecular Sciences (Online)
SN - 1661-6596
IS - 6
M1 - 3162
ER -
ID: 320660150