TY  - JOUR
A1  - Glatzel, Daniel Karl
A1  - Koeberle, Andreas
A1  - Pein, Helmut
A1  - Löser, Konstantin
A1  - Stark, Anna
A1  - Keksel, Nelli
A1  - Werz, Oliver
A1  - Müller, Rolf
A1  - Bischoff, Iris
A1  - Fürst, Robert
T1  - Acetyl-CoA carboxylase 1 regulates endothelial cell migration by shifting the phospholipid composition
T2  - Journal of lipid research
N2  - The enzyme acetyl-CoA carboxylase (ACC) plays a crucial role in fatty acid metabolism. In recent years, ACC has been recognized as a promising drug target for treating different diseases. However, the role of ACC in vascular endothelial cells (ECs) has been neglected so far. To characterize the role of ACC, we used the ACC inhibitor, soraphen A, as a chemical tool, and also a gene silencing approach. We found that ACC1 was the predominant isoform in human umbilical vein ECs as well as in human microvascular ECs and that soraphen A reduced the levels of malonyl-CoA. We revealed that ACC inhibition shifted the lipid composition of EC membranes. Accordingly, membrane fluidity, filopodia formation, and migratory capacity were reduced. The antimigratory action of soraphen A depended on an increase in the cellular proportion of PUFAs and, most importantly, on a decreased level of phosphatidylglycerol. Our study provides a causal link between ACC, membrane lipid composition, and cell migration in ECs. Soraphen A represents a useful chemical tool to investigate the role of fatty acid metabolism in ECs and ACC inhibition offers a new and valuable therapeutic perspective for the treatment of EC migration-related diseases.
KW  - membranes/fluidity
KW  - lipidomics
KW  - fatty acid/biosynthesis
KW  - phospholipids/phosphatidylglycerol
KW  - vascular biology/endothelial cells
KW  - soraphen
KW  - filopodia
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/77456
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-774567
SN  - 0022-2275
VL  - 59.2017
IS  - 2
SP  - 298
EP  - 311
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -