Summary of Study ST004323
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 PR002737. The data can be accessed directly via it's Project DOI: 10.21228/M8VZ6K 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 | ST004323 |
| Study Title | Human Hearts intrinsically increase cardiomyocyte mitosis following myocardial infarction |
| Study Summary | Background: Myocardial infarction (MI) is a leading cause of death worldwide and can eliminate up to a third of the cardiomyocytes (CMs) within the human heart. Although CMs undergo mitosis during early development, most CMs cease cell cycling soon after birth. In contrast, rodent MI models have shown that CMs increase mitosis in response to ischemia, however this has not been shown in humans. Methods: Using a unique pre-mortem post-MI human heart, immunostaining, bulk RNA sequencing, proteomics, metabolomics, single nucleus RNA sequencing and a novel post-MI human biopsy method, we investigated human CM mitosis post-MI. Results: We show that adult human CMs exhibit increased mitosis and cytokinesis in response to ischemia. Conclusions: Future development of therapeutics to enhance this intrinsic mitotic potential could lead to new treatments that reverse heart failure via cardiac regeneration. This uploaded dataset relates to the metabolomics (HILIC and AMIDE) performed on the unique infarcted human heart (5 days post-myocardial infarction) as compared to healthy donor hearts. Infarct samples consisted of non-ischemic right atrium (MI RA, technical replicates), partially ischemic right ventricle (MI RV, technical replicates), ischemic left ventricle (MI LV, technical replicates) and non-ischemic left ventricle donor tissue (Donor LV, biological replicates). |
| Institute | University of Sydney |
| Department | Charles Perkins Centre |
| Last Name | Hume |
| First Name | Robert |
| Address | John Hopkins Dr, Camperdown, NSW 2050, Australia |
| robert.hume@sydney.edu.au | |
| Phone | 0434848772 |
| Submit Date | 2025-10-22 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML, wiff |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-12-01 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002737 |
| Project DOI: | doi: 10.21228/M8VZ6K |
| Project Title: | Human Hearts intrinsically increase cardiomyocyte mitosis following myocardial infarction |
| Project Type: | Metabolomics |
| Project Summary: | Background: Myocardial infarction (MI) is a leading cause of death worldwide and can eliminate up to a third of the cardiomyocytes (CMs) within the human heart. Although CMs undergo mitosis during early development, most CMs cease cell cycling soon after birth. In contrast, rodent MI models have shown that CMs increase mitosis in response to ischemia, however this has not been shown in humans. Methods: Using a unique pre-mortem post-MI human heart, immunostaining, bulk RNA sequencing, proteomics, metabolomics, single nucleus RNA sequencing and a novel post-MI human biopsy method, we investigated human CM mitosis post-MI. Results: We show that adult human CMs exhibit increased mitosis and cytokinesis in response to ischemia. Conclusions: Future development of therapeutics to enhance this intrinsic mitotic potential could lead to new treatments that reverse heart failure via cardiac regeneration. |
| Institute: | University of Sydney |
| Department: | Charles Perkins Centre |
| Laboratory: | Centre for Heart Failure and Diseases of the Aorta |
| Last Name: | Robert |
| First Name: | Hume |
| Address: | John Hopkins Dr, Camperdown, NSW 2050, Australia |
| Email: | robert.hume@sydney.edu.au |
| Phone: | 0434848772 |
| Publications: | Circulation Research (in print) |
Subject:
| Subject ID: | SU004478 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Gender: | Male |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Sample source | Tissue Type | Group |
|---|---|---|---|---|
| SA505936 | HILIC_CASS7.080LV | Donor human heart left ventricle | LV | Donor |
| SA505937 | AMIDE_CASS7.080LV | Donor human heart left ventricle | LV | Donor |
| SA505938 | AMIDE_CASS7.004LV | Donor human heart left ventricle | LV | Donor |
| SA505939 | AMIDE_CASS6.056LV | Donor human heart left ventricle | LV | Donor |
| SA505940 | AMIDE_CASS6.048LV | Donor human heart left ventricle | LV | Donor |
| SA505941 | AMIDE_CASS3.145LV | Donor human heart left ventricle | LV | Donor |
| SA505942 | HILIC_CASS3.145LV | Donor human heart left ventricle | LV | Donor |
| SA505943 | HILIC_CASS6.048LV | Donor human heart left ventricle | LV | Donor |
| SA505944 | HILIC_CASS6.056LV | Donor human heart left ventricle | LV | Donor |
| SA505945 | HILIC_CASS7.004LV | Donor human heart left ventricle | LV | Donor |
| SA505946 | AMIDE_6.004ROB_LV28 | Infarcted human heart left ventricle | LV | Infarct |
| SA505947 | AMIDE_6.004ROB_LV26 | Infarcted human heart left ventricle | LV | Infarct |
| SA505948 | AMIDE_6.004ROB_LV18 | Infarcted human heart left ventricle | LV | Infarct |
| SA505949 | AMIDE_6.004ROB_LV14 | Infarcted human heart left ventricle | LV | Infarct |
| SA505950 | HILIC_6.004ROB_LV14 | Infarcted human heart left ventricle | LV | Infarct |
| SA505951 | HILIC_6.004ROB_LV10 | Infarcted human heart left ventricle | LV | Infarct |
| SA505952 | AMIDE_6.004ROB_LV10 | Infarcted human heart left ventricle | LV | Infarct |
| SA505953 | HILIC_6.004ROB_LV18 | Infarcted human heart left ventricle | LV | Infarct |
| SA505954 | HILIC_6.004ROB_LV26 | Infarcted human heart left ventricle | LV | Infarct |
| SA505955 | HILIC_6.004ROB_LV28 | Infarcted human heart left ventricle | LV | Infarct |
| SA505956 | AMIDE_6.004ROB_RA1_02 | Infarcted human heart right atrium | RA | Infarct (non-ischemic) |
| SA505957 | AMIDE_6.004ROB_RA2 | Infarcted human heart right atrium | RA | Infarct (non-ischemic) |
| SA505958 | HILIC_6.004ROB_RA1_02 | Infarcted human heart right atrium | RA | Infarct (non-ischemic) |
| SA505959 | HILIC_6.004ROB_RA2 | Infarcted human heart right atrium | RA | Infarct (non-ischemic) |
| SA505960 | AMIDE_6.004ROB_RV5 | Infarcted human heart right ventricle | RV | Infarct (semi-ischemic) |
| SA505961 | HILIC_6.004ROB_RV5 | Infarcted human heart right ventricle | RV | Infarct (semi-ischemic) |
| SA505962 | AMIDE_6.004ROB_RV4 | Infarcted human heart right ventricle | RV | Infarct (semi-ischemic) |
| SA505963 | HILIC_6.004ROB_RV4 | Infarcted human heart right ventricle | RV | Infarct (semi-ischemic) |
| SA505964 | AMIDE_6.004ROB_RV2 | Infarcted human heart right ventricle | RV | Infarct (semi-ischemic) |
| SA505965 | AMIDE_6.004ROB_RV1 | Infarcted human heart right ventricle | RV | Infarct (semi-ischemic) |
| SA505966 | HILIC_6.004ROB_RV1 | Infarcted human heart right ventricle | RV | Infarct (semi-ischemic) |
| SA505967 | HILIC_6.004ROB_RV2 | Infarcted human heart right ventricle | RV | Infarct (semi-ischemic) |
| SA505968 | HILIC_6.004ROB_RV3 | Infarcted human heart right ventricle | RV | Infarct (semi-ischemic) |
| SA505969 | AMIDE_6.004ROB_RV3 | Infarcted human heart right ventricle | RV | Infarct (semi-ischemic) |
| Showing results 1 to 34 of 34 |
Collection:
| Collection ID: | CO004471 |
| Collection Summary: | Human Heart tissue Donor hearts (Sydney Heart Bank) deemed suitable for heart transplantation but unable to be transplanted (for reasons including transportation logistics, immune incompatibility, and donor-recipient mismatch in size) were procured as previously described. These are not post-mortem samples. These non-diseased donor heart samples were from patients with a non-cardiac cause of death and no significant co-morbidities or cardiac risk factors (hence why the hearts would otherwise have been used for transplant). All hearts (non-diseased donor or ischemic) underwent formal pathological examination by clinical anatomical pathology to confirm either normal histological architecture or ischemic heart disease respectively. LV samples were obtained immediately after harvest and snap frozen in liquid nitrogen (-196 °C). The study was approved by the Human Ethics Committee of The University of Sydney (USYD # 2021/122). Procurement of a unique infarcted human heart The unique infarcted human heart was acquired from a 48yo male patient, originally on the national donor list, who suffered a catastrophic acute myocardial infarction (MI) due to a blockage of the left anterior descending artery. This patient suffered a cardiac arrest and at the Royal Prince Alfred Hospital, Sydney, whereby a coronary angioplasty and stent insertion could not be achieved. The patient was then kept on life support for 5d post-MI, at which point no neurological activity was detected and the patient was declared braindead. As the heart could not be used for transplant purposes, the next of kin kindly agreed to organ donation for research. The heart was then collected pre-mortem and cryopreserved within 15 mins i.e. fragments from the right atrium (MI RA), right ventricle (MI RV) and left ventricle (MI LV) were flash frozen and stored in liquid nitrogen, or fixed in 10% neutral buffered formalin (NBF, Sigma HTS012) overnight, before use. |
| Sample Type: | Heart |
| Storage Conditions: | Described in summary |
Treatment:
| Treatment ID: | TR004487 |
| Treatment Summary: | No treatment |
Sample Preparation:
| Sampleprep ID: | SP004484 |
| Sampleprep Summary: | Samples were fragmented with metal bead and an extraction buffer of equal methanol chloroform. Once tissue is fully lysed, chloroform and HPLC water is added before centrifugation. Two layers are aliquoted and separated which was ran in the mass spectrometer. |
Chromatography:
| Chromatography ID: | CH005471 |
| Instrument Name: | Sciex 6500+ |
| Column Name: | Waters XBridge AMIDE (100 x 2.1 mm, 3.5 µm) |
| Column Temperature: | 40°C |
| Flow Gradient: | 85%B and decreased after 8 min to 35% and continue to decrease to 2% at 9 min and maintained for 2 min before ramping back to 85% within 1 min |
| Flow Rate: | 0.25 mL/min |
| Solvent A: | 95% Water/5% Acetonitrile; 10 mM ammonium acetate (pH=9) |
| Solvent B: | 100% Acetonitrile |
| Chromatography Type: | HILIC |
| Chromatography ID: | CH005472 |
| Instrument Name: | Sciex 6500+ |
| Column Name: | Waters Atlantis HILIC Silica (150 x 2.1 mm, 3.5 µm) |
| Column Temperature: | 40°C |
| Flow Gradient: | Gradient at 95%B maintained at 4 min before decreasing to 40% at 9.5 min. Remaining 3 min at 40% and then increased to 95% for equilibration for 10 min. |
| Flow Rate: | 0.2 mL/min |
| Solvent A: | 100% Water; 10 mM Ammonium formate; 0.1% Formic acid |
| Solvent B: | 100% Acetonitrile; 0.1% Formic acid |
| Chromatography Type: | HILIC |
Analysis:
| Analysis ID: | AN007202 |
| Analysis Type: | MS |
| Chromatography ID: | CH005471 |
| Num Factors: | 4 |
| Num Metabolites: | 143 |
| Units: | AUC |
| Analysis ID: | AN007203 |
| Analysis Type: | MS |
| Chromatography ID: | CH005471 |
| Num Factors: | 4 |
| Num Metabolites: | 2 |
| Units: | AUC |
| Analysis ID: | AN007204 |
| Analysis Type: | MS |
| Chromatography ID: | CH005472 |
| Num Factors: | 4 |
| Num Metabolites: | 109 |
| Units: | AUC |
| Analysis ID: | AN007205 |
| Analysis Type: | MS |
| Chromatography ID: | CH005472 |
| Num Factors: | 4 |
| Num Metabolites: | 13 |
| Units: | AUC |
