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.

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Study IDST001434
Study TitleUntargeted lipidomics of liver to assess the potential protective role in atherosclerosis progression of A12 antibodies infusion into LDLR-/-mice
Study TypeLC-MS Untargeted Lipidomics
Study SummaryIn 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 NameFerrarini
First NameAlessia
AddressCalle de Melchor Fernández Almagro, 3, 28029 Madrid
Emailaferrarini@cnic.es
Phone+34 914 53 12 00
Submit Date2020-07-27
Num Groups3
Total Subjects18
PublicationsDOI. 10.1038/s41586-020-2993-2
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2020-09-25
Release Version1
Alessia Ferrarini Alessia Ferrarini
https://dx.doi.org/10.21228/M8CH6R
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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

Subject:

Subject ID:SU001508
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Antibody Group
SA121877A12_01A12
SA121878A12_06A12
SA121879A12_05A12
SA121880A12_02A12
SA121881A12_03A12
SA121882A12_04A12
SA121883B18_06B1.8
SA121884B18_05B1.8
SA121885B18_02B1.8
SA121886B18_01B1.8
SA121887B18_04B1.8
SA121888B18_03B1.8
SA121889CTRL_06PBS
SA121890CTRL_05PBS
SA121891CTRL_01PBS
SA121892CTRL_04PBS
SA121893CTRL_02PBS
SA121894CTRL_03PBS
SA121895QC_06QC
SA121896QC_07QC
SA121897QC_05QC
SA121898QC_03QC
SA121899QC_01QC
SA121900QC_02QC
SA121901QC_04QC
Showing results 1 to 25 of 25

Collection:

Collection ID:CO001503
Collection Summary:Liver were collected after mice sacrifice, frozen in liquid N2 and store at -80°C until the day of analysis.
Sample Type:Liver

Treatment:

Treatment ID:TR001523
Treatment Summary:LDLR-/-mice under high fat diet were injected with mA12-IgG2b and PBS or a B1-8 IgG2b isotype as control antibody

Sample Preparation:

Sampleprep ID:SP001516
Sampleprep Summary:Frozen liver tissues were lysed in 0.5X PBS (sample:solvent 1:10 ratio) containing 1 mg/mL butylhydroxytoluene (BHT) solution in methanol (proportion 200 µL per g of tissue), with FastPrep-24 5G instrument (MP Biomedicals, USA). 25 µL aliquots of homogenate were collected and stored at -80°C until lipidomic extraction. Tissue homogenates were thawed and extracted with methyl-tert-butylether (MTBE) as described in [Matyash, V., et al., Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. Journal of lipid research, 2008. 49(5): p. 1137-46]. 900 µL of organic phase were dried-out in speedvac and resuspended in 50 µL of ACN:H2O (20:80, v:v) just before injection.

Combined analysis:

Analysis ID AN002396 AN002397
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Dionex Ultimate 3000 Thermo Dionex Ultimate 3000
Column Agilent mRP-Recovery C18 column (100 x 0.5mm,5um) Agilent mRP-Recovery C18 column (100 x 0.5mm,5um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Orbitrap Elite Hybrid Ion Trap-Orbitrap Thermo Orbitrap Elite Hybrid Ion Trap-Orbitrap
Ion Mode POSITIVE NEGATIVE
Units peak area peak area

Chromatography:

Chromatography ID:CH001761
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:Agilent mRP-Recovery C18 column (100 x 0.5mm,5um)
Chromatography Type:Reversed phase

MS:

MS ID:MS002237
Analysis ID:AN002396
Instrument Name:Thermo Orbitrap Elite Hybrid Ion Trap-Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS was operating in full scan mode from 70 to 1700 m/z at 60000 resolution. Data processing was carried-out using Compound Discoverer (ThermoFisher; USA) with the Metaboprofiler node.
Ion Mode:POSITIVE
  
MS ID:MS002238
Analysis ID:AN002397
Instrument Name:Thermo Orbitrap Elite Hybrid Ion Trap-Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS was operating in full scan mode from 70 to 1700 m/z at 60000 resolution. Data processing was carried-out using Compound Discoverer (ThermoFisher; USA) with the Metaboprofiler node.
Ion Mode:NEGATIVE
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