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| Status |
Public on Nov 22, 2023 |
| Title |
Suppression of ANGPTL4 Reprograms Endothelial Cell Metabolism and Inhibits Angiogenesis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Angiopoietin-like 4 (ANGPTL4) is known to regulate various cellular and systemic functions. However, its cell-specific role in endothelial cells (ECs) function and metabolic homeostasis remains to be elucidated. Here, using endothelial-specific Angptl4 knock-out mice (Angptl4iEC), and transcriptomics and metabolic flux analysis, we demonstrate that ANGPTL4 is required for maintaining EC metabolic function vital for vascular permeability and angiogenesis. Knockdown of ANGPTL4 in ECs promotes lipase-mediated lipoprotein lipolysis, which results in increased fatty acid (FA) uptake and oxidation. This is also paralleled by a decrease in proper glucose utilization for angiogenic activation of ECs. Mice with endothelial-specific deletion of Angptl4 showed decreased pathological neovascularization with stable vessel structures characterized by increased pericyte coverage and reduced permeability. Together, our study denotes the role of endothelial-ANGPTL4 in regulating cellular metabolism and angiogenic functions of EC.
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| Overall design |
Comparative gene expression of early passage HUVECs treated with either siRNA to Non-silensing control (NS) or ANGPTL4 and or treated with Cobalt chloride (CoCl2) or XEN445 for 24 hours.
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| Contributor(s) |
Chaube B, Citrin KM, Sahraei M, Singh AK, Saenz de Urturi D, Ding W, Pierce RW, Raaisa R, Cardone R, Kibbey R, Fernandez-Hernando C, Suarez Y |
| Citation(s) |
38086791 |
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| Submission date |
Aug 12, 2022 |
| Last update date |
Jan 02, 2024 |
| Contact name |
Bal Krishna Chaube |
| E-mail(s) |
[email protected]
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| Organization name |
Yale University
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| Department |
Comparative Medicine
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| Lab |
414K
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| Street address |
Amistad Research Building, Amistad St
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| City |
New Haven |
| State/province |
CT |
| ZIP/Postal code |
06520 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (30)
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| GSM6451035 |
HUVECs cells Biol Rep 1, siANGPTL4 |
| GSM6451036 |
HUVECs cells Biol Rep 2, siANGPTL4 |
| GSM6451037 |
HUVECs cells Biol Rep 3, siANGPTL4 |
| GSM6451038 |
HUVECs cells Biol Rep 1, NS VC1 |
| GSM6451039 |
HUVECs cells Biol Rep 2, NS VC2 |
| GSM6451040 |
HUVECs cells Biol Rep 3, NS VC3 |
| GSM6451041 |
HUVECs cells Biol Rep 1, siANGPTL4 VC1 |
| GSM6451042 |
HUVECs cells Biol Rep 2, siANGPTL4 VC2 |
| GSM6451043 |
HUVECs cells Biol Rep 3, siANGPTL4 VC3 |
| GSM6451044 |
HUVECs cells Biol Reph 1, NS CoCl2 100 µM |
| GSM6451045 |
HUVECs cells Biol Rep 2, NS CoCl2 100 µM |
| GSM6451046 |
HUVECs cells Biol Rep 3, NS CoCl2 100 µM |
| GSM6451047 |
HUVECs cells Biol Rep 1, siANGPTL4 CoCl2 100 µM |
| GSM6451048 |
HUVECs cells Biol Rep 2, siANGPTL4 CoCl2 100 µM |
| GSM6451049 |
HUVECs cells Biol Rep 3, siANGPTL4 CoCl2 100 µM |
| GSM6451050 |
HUVECs cells Biol Rep 1, NS DMSO1 |
| GSM6451051 |
HUVECs cells Biol Rep 2, NS DMSO2 |
| GSM6451052 |
HUVECs cells Biol Rep 3, NS DMSO3 |
| GSM6451053 |
HUVECs cells Biol Rep 1, siANGPTL4 DMSO1 |
| GSM6451054 |
HUVECs cells Biol Rep 2, siANGPTL4 DMSO2 |
| GSM6451055 |
HUVECs cells Biol Rep 3, siANGPTL4 DMSO3 |
| GSM6451056 |
HUVECs cells Biol Rep 1, NS-XEN445 10 µM |
| GSM6451057 |
HUVECs cells Biol Rep 2, NS-XEN445 10 µM |
| GSM6451058 |
HUVECs cells Biol Rep 3, NS-XEN445 10 µM |
| GSM6451059 |
HUVECs cells Biol Rep 1, siANGPTL4-XEN445 10 µM |
| GSM6451060 |
HUVECs cells Biol Rep 2, siANGPTL4-XEN445 10 µM |
| GSM6451061 |
HUVECs cells Biol Rep 3, siANGPTL4-XEN445 10 µM |
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| Relations |
| BioProject |
PRJNA869060 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE211128_NS-vs-siANG-Basal-Raw-gene-counts.txt.gz |
974.7 Kb |
(ftp)(http) |
TXT |
| GSE211128_NS-vs-siANGPTL4-Hypoxia-Raw-gene-counts.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| GSE211128_NS-vs-siANGPTL4-XEN445-Raw-gene-counts.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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