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 |
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Collection:
| Collection ID: | CO002836 |
| Collection Summary: | LV tissue from patients undergoing CABG was sampled from two or more pre-determined areas (as guided by CMR) on the beating heart during surgery: 1) a region of viable myocardium with inducible ischemia [‘ischemic’ biopsy]; 2) a region of remote myocardium with normal contractility, no qualitative evidence of inducible hypoperfusion on perfusion imaging, and without infarct pattern LGE [‘remote’ biopsy]. The a priori plan was to acquire paired biopsies, permitting high energy phosphate (HEP) quantification and LC-MS for each individual patient. Surgical discretion, however, resulted in some patients not undergoing paired tissue collection. Conversely, where deemed safe, extra tissue was acquired for single-nuclei RNA sequencing. The CABG biopsies were performed on the beating heart (prior to aortic cross-clamp, cardioplegia and hypothermia in the cases using cardiopulmonary bypass) with a Tru-Cut® needle or scalpel by the consultant cardiac surgeon. The majority of operations were performed off-pump without cardiopulmonary bypass. Samples were immediately clamp-frozen in theatre using a Wollenberg clamp (manufactured by Josh Firman, LMB Workshop, UK) which had been pre-cooled in liquid nitrogen until tissue acquisition. The clamps were then reopened, and the tissue rapidly transferred into Eppendorf tubes (pre-cooled in dry ice) before storage at -80ºC awaiting further analysis. |
| Collection Protocol Filename: | Protocol_AMBITION.pdf |
| Sample Type: | Heart |
