Summary of Study ST001434
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 PR000985. The data can be accessed directly via it's Project DOI: 10.21228/M8CH6R 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 | ST001434 |
| Study Title | Untargeted lipidomics of liver to assess the potential protective role in atherosclerosis progression of A12 antibodies infusion into LDLR-/-mice |
| Study Type | LC-MS Untargeted Lipidomics |
| Study Summary | In order to assess the therapeutic potential of A12 antibodies in atherosclerosis, untargeted lipidomics of liver samples was performed. LDLR-/-mice were treated with a fully murine version of the A12 antibody (mA12-IgG2b), with the isotype control antibody mB1.8-IgG2b (n=16) or with PBS as controls. |
| Institute | Centro Nacional de Investigaciones Cardiovasculares Carlos III |
| Last Name | Ferrarini |
| First Name | Alessia |
| Address | Calle de Melchor Fernández Almagro, 3, 28029 Madrid |
| aferrarini@cnic.es | |
| Phone | +34 914 53 12 00 |
| Submit Date | 2020-07-27 |
| Num Groups | 3 |
| Total Subjects | 18 |
| Publications | DOI. 10.1038/s41586-020-2993-2 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2020-09-25 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR000985 |
| Project DOI: | doi: 10.21228/M8CH6R |
| Project Title: | ALDH4A1 is a novel atherosclerosis auto-antigen and a target of protective 6 antibodies |
| Project Type: | LC-MS Untargeted Lipidomics |
| Project Summary: | Cardiovascular disease (CVD) is the leading cause of mortality in the world, with most CVD deaths resulting from myocardial infarction and stroke. The main cause underlying thrombosis and cardiovascular events is atherosclerosis, an inflammatory disease that can remain asymptomatic for long periods of time. There is an urgent need for new therapeutic and diagnostic options in this area. Atherosclerotic plaques have long been known to contain autoantibodies 1, 2, and there is a well-accepted connection between atherosclerosis and autoimmunity 3. However, the immunogenic trigger and the impact of the autoantibody response during atherosclerosis are not well understood 3, 4, 5. Here we performed a high-throughput single-cell analysis of the atherosclerosis-associated antibody repertoire. Antibody gene sequencing of more than 1700 B cells from atherogenic LDLR-/- mice and control animals identified 56 antibodies expressed by in-vivo-expanded clones of B lymphocytes in the context of atherosclerosis. A third of the expanded antibodies showed reactivity against the atherosclerotic plaque, indicating that various antigens in the lesion can trigger antibody responses. A deep proteomics analysis revealed aldehyde dehydrogenase 4 family member A1 (ALDH4A1), a mitochondrial dehydrogenase involved in proline metabolism, as target antigen of one of these autoantibodies, A12. We show that ALDH4A1 distribution is altered during atherosclerosis and circulating levels of ALDH4A1 are increased in mice and humans with atherosclerosis, supporting the potential use of ALDH4A1 as disease biomarker. A12 antibody infusion into LDLR-/- mice delayed plaque formation and reduced circulating levels of free cholesterol and LDL suggesting that anti-ALDH4A1 antibodies can play a protective role in atherosclerosis progression and might have therapeutic potential. Our study reveals a new auto-antigenic trigger target of the atherosclerosis-associated antibody response and opens new avenues for diagnostic and therapeutic interventions in CVD. |
| Institute: | Centro Nacional de Investigaciones Cardiovasculares Carlos III |
| Last Name: | Ferrarini |
| First Name: | Alessia |
| Address: | Calle de Melchor Fernández Almagro, 3, 28029 Madrid |
| Email: | aferrarini@cnic.es |
| Phone: | +34 914 53 12 00 |
| Publications: | DOI. 10.1038/s41586-020-2993-2 |
