TY - JOUR
T1 - Vascular Metabolism as Driver of Atherosclerosis
T2 - Linking Endothelial Metabolism to Inflammation
AU - Dzobo, Kim E
AU - Hanford, Katie M L
AU - Kroon, Jeffrey
PY - 2021/5/17
Y1 - 2021/5/17
N2 - The endothelium is a crucial regulator of vascular homeostasis by controlling barrier integrity as well acting as an important signal transducer, thereby illustrating that endothelial cells are not inert cells. In the context of atherosclerosis, this barrier function is impaired and endothelial cells become activated, resulting in the upregulation of adhesion molecules, secretion of cytokines and chemokines and internalization of integrins. Finally, this leads to increased vessel permeability, thereby facilitating leukocyte extravasation as well as fostering a pro-inflammatory environment. Additionally, activated endothelial cells can form migrating tip cells and proliferative stalk cells, resulting in the formation of new blood vessels. Emerging evidence has accumulated indicating that cellular metabolism is crucial in fueling these pro-atherosclerotic processes, including neovascularization and inflammation, thereby contributing to plaque progression and altering plaque stability. Therefore, further research is necessary to unravel the complex mechanisms underlying endothelial cell metabolic changes, and exploit this knowledge for finding and developing potential future therapeutic strategies. In this review we discuss the metabolic alterations endothelial cells undergo in the context of inflammation and atherosclerosis and how this relates to changes in endothelial functioning. Finally, we will describe several metabolic targets that are currently being used for therapeutic interventions.
AB - The endothelium is a crucial regulator of vascular homeostasis by controlling barrier integrity as well acting as an important signal transducer, thereby illustrating that endothelial cells are not inert cells. In the context of atherosclerosis, this barrier function is impaired and endothelial cells become activated, resulting in the upregulation of adhesion molecules, secretion of cytokines and chemokines and internalization of integrins. Finally, this leads to increased vessel permeability, thereby facilitating leukocyte extravasation as well as fostering a pro-inflammatory environment. Additionally, activated endothelial cells can form migrating tip cells and proliferative stalk cells, resulting in the formation of new blood vessels. Emerging evidence has accumulated indicating that cellular metabolism is crucial in fueling these pro-atherosclerotic processes, including neovascularization and inflammation, thereby contributing to plaque progression and altering plaque stability. Therefore, further research is necessary to unravel the complex mechanisms underlying endothelial cell metabolic changes, and exploit this knowledge for finding and developing potential future therapeutic strategies. In this review we discuss the metabolic alterations endothelial cells undergo in the context of inflammation and atherosclerosis and how this relates to changes in endothelial functioning. Finally, we will describe several metabolic targets that are currently being used for therapeutic interventions.
U2 - https://doi.org/10.20900/immunometab20210020
DO - https://doi.org/10.20900/immunometab20210020
M3 - Article
C2 - 34084561
SN - 2084-6835
VL - 3
SP - e210020
JO - Immunometabolism
JF - Immunometabolism
IS - 3
ER -