PUBLICATION
Electron Transfer Flavoprotein (ETF) α Controls Blood Vessel Development by Regulating Endothelial Mitochondrial Bioenergetics and Oxygen Consumption
- Authors
- Yan, Y., Xu, Y., Yang, X., Li, Z., Niu, K., Liu, C., Zhao, M., Xiao, Q., Wu, W.
- ID
- ZDB-PUB-220323-23
- Date
- 2022
- Source
- Oxidative medicine and cellular longevity 2022: 7969916 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Electron Transport
- Electron-Transferring Flavoproteins*/genetics
- Electron-Transferring Flavoproteins*/metabolism
- Endothelial Cells/metabolism
- Oxygen Consumption
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 35313640 Full text @ Oxid Med Cell Longev
Citation
Yan, Y., Xu, Y., Yang, X., Li, Z., Niu, K., Liu, C., Zhao, M., Xiao, Q., Wu, W. (2022) Electron Transfer Flavoprotein (ETF) α Controls Blood Vessel Development by Regulating Endothelial Mitochondrial Bioenergetics and Oxygen Consumption. Oxidative medicine and cellular longevity. 2022:7969916.
Abstract
While impairment of vascular homeostasis induced by hypercholesterolemia is the first step of cardiovascular diseases, the molecular mechanism behind such impairment is not well known. Here, we reported that high-cholesterol diet (HCD) induced defective vessel sprouting in zebrafish larvae. Electron transfer flavoprotein subunit α (ETFα) (encoded by the ETFA gene), a protein that mediates transfer of electrons from a series of mitochondrial flavoenzymes to the respiratory chain, was downregulated in HCD-fed zebrafish and in endothelial cells treated with oxidized low-density lipoprotein. Knockdown of ETFα with morpholino antisense oligonucleotides reproduced vascular sprouting defects in zebrafish larvae, while replenishing with exogeneous ETFA mRNA could successfully rescue these defects. ETFA knockdown in endothelial cells reduces cell migration, proliferation, and tube formation in vitro. Finally, knockdown of ETFA in endothelial cells also reduced fatty acid oxidation, oxygen consumption rate, and hypoxia-inducible factor-1α (HIF1α) protein levels. Taken together, we demonstrate that downregulation of ETFα is involved in hypercholesterolemia-induced defective vessel sprouting in zebrafish larvae via inhibition of endothelial proliferation and migration. The molecular mechanism behind this phenomenon is the decrease of HIF1α induced by downregulation of ETFα in endothelial cells. This work suggests that disturbance of ETFα-mediated oxygen homeostasis is one of the mechanisms behind hypercholesterolemia-induced vascular dysfunction.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping