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.

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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 IDST002736
Study TitleAssessing mitochondrial bioenergetics in coronary artery disease: A translational multiomic tissue study in humans (The AMBITION study).
Study SummaryBackground: 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 NameJones
First NameRichard Elis
AddressRoyal Brompton Hospital
Emailrichard.jones34@nhs.net
Phone02073528121
Submit Date2023-05-29
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-07-06
Release Version1
Richard Elis Jones Richard Elis Jones
https://dx.doi.org/10.21228/M8ZM7F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001700
Project DOI:doi: 10.21228/M8ZM7F
Project Title:Assessing mitochondrial bioenergetics in coronary artery disease: A translational multiomic tissue study in humans (The AMBITION study).
Project 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
Email:richard.jones34@nhs.net
Phone:02073528121

Subject:

Subject ID:SU002843
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Male and female

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA288685RJ_3CC1Ischemic
SA288686RJ_4DD1Ischemic
SA288687RJ_10JJ1Ischemic
SA288688RJ_2BB1Ischemic
SA288689RJ_29CF2Ischemic
SA288690RJ_21DF1Ischemic
SA288691RJ_22EG1Ischemic
SA288692RJ_28BE1Ischemic
SA288693RJ_8HH1Ischemic
SA288694RJ_24IK2Ischemic
SA288695RJ_26KM1Ischemic
SA288696RJ_25JL1Ischemic
SA288697RJ_23FH1Ischemic
SA288698RJ_9II1Ischemic
SA288699RJ_30DG1Ischemic
SA288700RJ_27AD1Ischemic
SA288701RJ_6KK1Ischemic
SA288702RJ_20CE1Ischemic
SA288703RJ_16IJ1Ischemic
SA288704RJ_32FI1Ischemic
SA288705RJ_15GH1Ischemic
SA288706RJ_33GJ1Ischemic
SA288707RJ_14EF1Ischemic
SA288708RJ_13CD1Ischemic
SA288709RJ_34HK1Ischemic
SA288710RJ_17KL1Ischemic
SA288711RJ_19BD1Ischemic
SA288712RJ_11LL1Ischemic
SA288713RJ_18AC1Ischemic
SA288714RJ_12AB1Ischemic
SA288715RJ_31EH1Ischemic
SA288716RJ_26PN2Remote
SA288717RJ_33TQ1Remote
SA288718RJ_34SP1Remote
SA288719RJ_32UR1Remote
SA288720RJ_29XU1Remote
SA288721RJ_25SQ1Remote
SA288722RJ_31VS1Remote
SA288723RJ_28YV1Remote
SA288724RJ_30WT1Remote
SA288725RJ_27ZW1Remote
SA288726RJ_4WW1Remote
SA288727RJ_15TS1Remote
SA288728RJ_16RQ1Remote
SA288729RJ_17PO1Remote
SA288730RJ_14VU1Remote
SA288731RJ_13XW1Remote
SA288732RJ_10QQ1Remote
SA288733RJ_11OO1Remote
SA288734RJ_12ZY1Remote
SA288735RJ_18ZX1Remote
SA288736RJ_19YW1Remote
SA288737RJ_6PP1Remote
SA288738RJ_8SS1Remote
SA288739RJ_9RR1Remote
SA288740RJ_5VV1Remote
SA288741RJ_2YY1Remote
SA288742RJ_20XV1Remote
SA288743RJ_21WU1Remote
SA288744RJ_22VT1Remote
SA288745RJ_24TR2Remote
Showing results 1 to 61 of 61

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

Treatment:

Treatment ID:TR002852
Treatment Summary:'Ischemic' or 'remote' biopsy as determined by preoperative stress perfusion cardiovascular magnetic resonance.

Sample Preparation:

Sampleprep ID:SP002849
Sampleprep Summary:Frozen LV tissue samples (~1-5mg) were weighed into Precellys tubes (Stretton Scientific Ltd., Derbyshire, UK), and an exact volume of extraction solution (50% methanol, 30% acetonitrile and 20% water) was added to obtain 40 mg specimen per ml of extraction solution, permitting comparisons between experimental conditions for the same metabolite. The samples were subsequently lysed after the addition of 3 ceramic beads using a Precellys 24 tissue homogenizer (Bertin Corp, Rockville, MD 20850, USA. 5500 r.p.m for 15 seconds × 2) and finally centrifuged (16,162 × g for 10 min at 4 °C). The supernatant was transferred into glass vials (Microsolv Technology Corp., Leland, NC 28451, USA) and stored at −80 °C until LC–MS analysis.

Combined analysis:

Analysis ID AN004438
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

MS:

MS ID:MS004185
Analysis ID:AN004438
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Metabolites were measured using a Thermo Scientific Q Exactive Hybrid Quadrupole-Orbitrap Mass spectrometer (HRMS) coupled to a Dionex Ultimate 3000 UHPLC. The mass spectrometer was operated in full-scan, polarity-switching mode, with the spray voltage set to +4.5 kV/-3.5 kV, the heated capillary held at 320 °C, and the auxiliary gas heater kept at 280 °C. The sheath gas flow was programmed to 55 units, the auxiliary gas flow was programmed to 15 units, and the sweep gas flow was programmed to 0 unit. HRMS data acquisition was performed in a range of m/z = 70–900, with the resolution set at 70,000, the AGC target at 1 × 106, and the maximum injection time (Max IT) at 120 ms. Metabolite identities were confirmed using two parameters: (1) precursor ion m/z was matched within 5 ppm of theoretical mass predicted by the chemical formula; (2) the retention time of metabolites was within 5% of the retention time of a purified standard run with the same chromatographic method. Each sample underwent 3 analytical repeats with subsequent peak annotation and chromatogram review and peak area integration were performed using the Thermo Fisher software Tracefinder 5.0. The peak area for each detected metabolite was subjected to the “Filtering 80% Rule”, half minimum missing value imputation, and normalized against the total ion count (TIC) to correct any variations introduced from sample handling through instrument analysis. Samples were excluded after performing testing for outliers based on geometric distances of each point in the PCA score analysis as part of the muma package (v.1.4)
Ion Mode:UNSPECIFIED
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