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Combined glucocorticoid resistance and hyperlactatemia contributes to lethal shock in sepsis
Tijdschriftbijdrage - Tijdschriftartikel
Sepsis is a potentially lethal syndrome resulting from a maladaptive response to infection. Upon infection, glucocorticoids are produced as a part of the compensatory response to tolerate sepsis. This tolerance is, however, mitigated in sepsis due to a quickly induced glucocorticoid resistance at the level of the glucocorticoid receptor. Here, we show that defects in the glucocorticoid receptor signaling pathway aggravate sepsis pathophysiology by lowering lactate clearance and sensitizing mice to lactate-induced toxicity. The latter is exerted via an uncontrolled production of vascular endothelial growth factor, resulting in vascular leakage and collapse with severe hypotension, organ damage, and death, all being typical features of a lethal form of sepsis. In conclusion, sepsis leads to glucocorticoid receptor failure and hyperlactatemia, which collectively leads to a lethal vascular collapse.
Tijdschrift: Cell Metabolism
ISSN: 1550-4131
Issue: 9
Volume: 33
Pagina's: 1763 - +
Jaar van publicatie:2021
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:10
CSS-citation score:1
Auteurs:International
Authors from:Government, Higher Education
Toegankelijkheid:Closed
- Zie ook: Combined glucocorticoid resistance and hyperlactatemia contributes to lethal shock in sepsis
- Zie ook: Combined glucocorticoid resistance and hyperlactatemia contributes to lethal shock in sepsis
- Zie ook: Combined glucocorticoid resistance and hyperlactatemia contributes to lethal shock in sepsis.