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

International Journal of Molecular Sciences

Pär Ingemar Johansson¹  Hanne H. Henriksen¹  Alexía Rós Viktorsdóttir²  Arnar Ingi Vilhjálmsson²  Andreas Bergmann²  Ósk Anuforo²  Aris Kotronoulas²  Adrián López García de Lomana²  Óttar Rolfsson²  Rósa Sigurðardóttir²  Sarah McGarrity²  Charles E. Wade³  Leifur Franzson⁴  Haraldur Halldórsson⁵ 

[1] Center for Endotheliomics CAG, Rigshospitalet, 2200 Copenhagen, Denmark;Center for Systems Biology, University of Iceland, 101 Reykjavík, Iceland;Center for Translational Injury Research, The University of Texas Health Science Center, Houston, TX 77030, USA;Landspítali-Háskólasjúkrahús, 101 Reykjavík, Iceland;Medical Department, University of Iceland, 102 Reykjavík, Iceland;

关键词: metabolomics;    catecholamines;    vascular permeability;    endotheliopathy;    major trauma;   

DOI  :  10.3390/ijms23063162

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown