Summary of Study ST002736
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 PR001700. The data can be accessed directly via it's Project DOI: 10.21228/M8ZM7F 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 | ST002736 |
Study Title | Assessing mitochondrial bioenergetics in coronary artery disease: A translational multiomic tissue study in humans (The AMBITION study). |
Study Summary | Background: Severe or recurrent myocardial ischemia can lead to chronic left ventricular (LV) dysfunction and heart failure in patients with coronary artery disease (CAD). Objectives: To assess the multiomic profile of LV myocardium in patients with stable CAD. Methods: Patients undergoing coronary artery bypass grafting (CABG) had preoperative quantitative stress perfusion cardiovascular magnetic resonance. During surgery, paired transmural LV biopsies were acquired on the beating heart from a region of inducible ischemia, and a remote LV segment. LV samples from human organ donors were used as controls. Myocardial biopsies underwent high-energy phosphate quantification, liquid chromatography-mass spectrometry and single-nuclei ribonucleic acid sequencing. Results: From 33 patients, 63 LV biopsies were acquired on the beating heart during CABG (mean age 60±9 years, median LV ejection fraction 67% [IQR: 61-71%]). Analysis of LV samples from 11 essentially healthy donor hearts were included. The global myocardial ATP/ADP ratio was reduced in CAD patients as compared to donor LV tissue (median [IQR]: 2.2 [1.5-2.8] versus 7.4 [6.8-8.6], P=0.001), with increased expression of oxidative phosphorylation (OXPHOS) genes encoding the electron transport chain complexes across multiple cell types. Paired analyses of biopsies obtained during CABG from LV segments with or without inducible ischemia revealed no significant difference in the ATP/ADP ratio (P=0.36), broader metabolic profile or expression of ventricular cardiomyocyte genes implicated in OXPHOS. Conclusions: Our results suggest that viable human myocardium in patients with stable CAD has global alterations in bioenergetic and transcriptional profile without large regional differences between areas with or without inducible ischemia. |
Institute | Imperial College London |
Last Name | Jones |
First Name | Richard Elis |
Address | Royal Brompton Hospital |
richard.jones34@nhs.net | |
Phone | 02073528121 |
Submit Date | 2023-05-29 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2023-07-06 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
Analysis ID | AN004438 |
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Analysis type | MS |
Chromatography type | HILIC |
Chromatography system | Thermo Dionex Ultimate 3000 |
Column | SeQuant ZIC- pHILIC (150 x 2.1mm,5um) |
MS Type | ESI |
MS instrument type | Orbitrap |
MS instrument name | Thermo Q Exactive Orbitrap |
Ion Mode | UNSPECIFIED |
Units | peak area |
Chromatography:
Chromatography ID: | CH003334 |
Chromatography Summary: | HILIC chromatographic separation of metabolites was achieved using a Millipore Sequant ZIC-pHILIC analytical column (5 µm, 2.1 × 150 mm) equipped with a 2.1 × 20 mm guard column (both 5 mm particle size) with a binary solvent system. Solvent A was 20 mM ammonium carbonate, 0.05% ammonium hydroxide; Solvent B was acetonitrile. The column oven and autosampler tray were kept at 40 °C and 4 °C, respectively. The chromatographic gradient was run at a flow rate of 0.200 mL/min as follows: 0–2 min: 80% B; 2-17 min: linear gradient from 80% B to 20% B; 17-17.1 min: linear gradient from 20% B to 80% B; 17.1-22.5 min: hold at 80% B. Samples were randomized and analysed with LC–MS in a blinded manner with an injection volume was 5 µl. Pooled samples were generated from an equal mixture of all individual samples and analysed interspersed, at regular intervals, within the sample sequence as a quality control. Each sample was analysed with three analytical replicates. |
Instrument Name: | Thermo Dionex Ultimate 3000 |
Column Name: | SeQuant ZIC- pHILIC (150 x 2.1mm,5um) |
Column Temperature: | 40 |
Flow Gradient: | 0–2 min: 80% B; 2-17 min: linear gradient from 80% B to 20% B; 17-17.1 min: linear gradient from 20% B to 80% B; 17.1-22.5 min: hold at 80% B |
Flow Rate: | 0.200 mL/min |
Solvent A: | 20 mM ammonium carbonate, 0.05% ammonium hydroxide |
Solvent B: | acetonitrile |
Chromatography Type: | HILIC |