Inflammatory activation of endothelial cells increases glycolysis and oxygen consumption despite inhibiting cell proliferation.
FEBS Open Bio
; 11(6): 1719-1730, 2021 06.
Article
in En
| MEDLINE
| ID: mdl-33979025
ABSTRACT
Endothelial cell function and metabolism are closely linked to differential use of energy substrate sources and combustion. While endothelial cell migration is promoted by 2-phosphofructokinase-6/fructose-2,6-bisphosphatase (PFKFB3)-driven glycolysis, proliferation also depends on fatty acid oxidation for dNTP synthesis. We show that inflammatory activation of human umbilical vein endothelial cells (HUVECs) by interleukin-1ß (IL-1ß), despite inhibiting proliferation, promotes a shift toward more metabolically active phenotype. This was reflected in increased cellular glucose uptake and consumption, which was preceded by an increase in PFKFB3 mRNA and protein expression. However, despite a modest increase in extracellular acidification rates, the increase in glycolysis did not correlate with extracellular lactate accumulation. Accordingly, IL-1ß stimulation also increased oxygen consumption rate, but without a concomitant rise in fatty acid oxidation. Together, this suggests that the IL-1ß-stimulated energy shift is driven by shunting of glucose-derived pyruvate into mitochondria to maintain elevated oxygen consumption in HUVECs. We also revealed a marked donor-dependent variation in the amplitude of the metabolic response to IL-1ß and postulate that the donor-specific response should be taken into account when considering targeting dysregulated endothelial cell metabolism.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Human Umbilical Vein Endothelial Cells
/
Inflammation
Limits:
Humans
Language:
En
Journal:
FEBS Open Bio
Year:
2021
Document type:
Article
Affiliation country:
Norway