Summary of Study ST002873
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001795. The data can be accessed directly via it's Project DOI: 10.21228/M8PM7Z This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002873 |
| Study Title | The ganglioside GM3 protects against abdominal aortic aneurysm (AAA) by suppressing ferroptosis |
| Study Summary | Background: Abdominal aortic aneurysm (AAA) is a potentially life-threatening condition, but approved medical therapies to prevent AAA progression and rupture are currently lacking. Sphingolipids metabolism disorders are associated with the occurrence and development of AAA. It has been discovered that ganglioside GM3, a sialic acid-containing type of glycosphingolipid, plays a protective role in atherosclerosis which is an important risk factor for AAA, but the potential contribution of GM3 to AAA development has not been investigated. Methods: We performed a metabolomics study to evaluated GM3 level in plasma of human AAA patients. We profiled GM3 synthase (ST3GAL5) expression in the mouse model of aneurysm and human AAA tissues through western blotting and immunofluorescence staining. RNA sequencing, proteomic analysis, affinity purification and mass spectrometry, surface plasmon resonance (SPR) analysis, and functional studies were used to dissect the molecular mechanism of GM3-regulating ferroptosis. We conditionally deleted and overexpressed St3gal5 in smooth muscle cells (SMCs) in vivo to investigate its role in AAA. Results: We found significantly reduced plasma levels of the GM3 in human AAA patients. GM3 content and ST3GAL5 expression were all decreased in abdominal aortic VSMCs in AAA patients and mouse model. RNA-sequencing analysis showed that ST3GAL5 silencing in human aortic SMCs (HASMCs) induced ferroptosis. Importantly, we showed that GM3 interacted directly with the extracellular domain of transferrin receptor 1 (TFR1), a cell membrane protein critical for cellular iron uptake, disrupted its interaction with holo-transferrin. SMC-specific St3gal5 knockout exacerbated iron accumulation at lesion sites and significantly promoted AAA development, while GM3 supplementation suppressed lipid peroxidation, reduced iron deposition in aortic VSMCs and markedly decreased AAA incidence. Conclusions: Together, these results suggest that GM3 dysregulation promotes ferroptosis of VSMCs in AAA. Furthermore, GM3 may constitute a new therapeutic target for the treatment of AAA. |
| Institute | Tianjin Medical University |
| Last Name | Li |
| First Name | Kan |
| Address | Tianjin Medical University, Tianjin, China., Tianjin, Tianjin, 300070, China |
| likan1115@tmu.edu.cn | |
| Phone | 18853602951 |
| Submit Date | 2023-09-20 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML, wiff |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-01-01 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004709 | AN004710 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Reversed phase |
| Chromatography system | Waters Acquity | Waters Acquity |
| Column | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) |
| MS Type | ESI | ESI |
| MS instrument type | QTRAP | QTRAP |
| MS instrument name | ABI Sciex 5500 QTrap | ABI Sciex 5500 QTrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | ng/mL | ng/mL |
MS:
| MS ID: | MS004455 |
| Analysis ID: | AN004709 |
| Instrument Name: | ABI Sciex 5500 QTrap |
| Instrument Type: | QTRAP |
| MS Type: | ESI |
| MS Comments: | Raw data were processed using MultiQuant 3.0.3. Metabolite levels were calculated as the ratio of their concentrations relative to a standard sample. Quantifing the targeted metabolites by area under the curve used expected retention time. |
| Ion Mode: | POSITIVE |
| MS ID: | MS004456 |
| Analysis ID: | AN004710 |
| Instrument Name: | ABI Sciex 5500 QTrap |
| Instrument Type: | QTRAP |
| MS Type: | ESI |
| MS Comments: | Raw data were processed using MultiQuant 3.0.3. Metabolite levels were calculated as the ratio of their concentrations relative to a standard sample. Quantifing the targeted metabolites by area under the curve used expected retention time. |
| Ion Mode: | NEGATIVE |
