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| Status |
Public on May 30, 2023 |
| Title |
Epicardial Placement of Human Placental Membrane Protects from Heart Injury in a Swine Model of Myocardial Infarction |
| Organism |
Sus scrofa domesticus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Introduction: Cardiac ischemic reperfusion injury (IRI) is paradoxically instigated by re-establishing blood-flow to ischemic myocardium typically from a myocardial infarction (MI). Although revascularization following MI remains the standard of care, effective strategies remain limited to prevent or attenuate IRI. We hypothesized that epicardial placement of human placental amnion/chorion (HPAC) grafts will protect against IRI. Methods: Using a clinically relevant model of IRI, swine were subjected to 45 minutes percutaneous ischemia followed with (MI+HPAC, n=3) or without (MI only, n=3) HPAC. Cardiac function was assessed by echocardiography, and regional punch biopsies were collected 14 days post-operatively. A deep phenotyping approach was implemented by using histological interrogation and incorporating global proteomics and transcriptomics in non-ischemic, ischemic, and border zone biopsies. Results: Our results established HPAC limited the extent of cardiac injury by 50% (11.02.0% vs 22.03.0%, p=0.039) and preserved ejection fraction in HPAC-treated swine (46.8±2.7% vs 35.8±4.5%, p=0.014). We present comprehensive transcriptome and proteome profiles of infarct (IZ), border (BZ), and remote (RZ) zone punch biopsies from swine myocardium during the proliferative cardiac repair phase 14 days post-MI. Both HPAC-treated and untreated tissues showed regional dynamic responses, whereas only HPAC-treated IZ revealed active immune and extracellular matrix remodeling. Decreased endoplasmic reticulum (ER)-dependent protein secretion and increased anti-apoptotic and anti-inflammatory responses were measured in HPAC-treated biopsies. Discussion: We provide quantitative evidence HPAC reduced cardiac injury from MI in a preclinical swine model, establishing a potential new therapeutic strategy for IRI.
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| Overall design |
comparative gene expression profiling analysis of RNA-seq data for porcine elicited or not elicited and myocardial infarction(MI) and treated(Tx) or untreated with HPAC.
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| Contributor(s) |
Skaria R, Lopez-Schultz M, Konhilas J |
| Citation(s) |
37849042 |
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| Submission date |
Mar 23, 2023 |
| Last update date |
Oct 26, 2023 |
| Contact name |
Marissa Anne Lopez-Pier |
| E-mail(s) |
mal1@arizona.edu
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| Phone |
5202718292
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| Organization name |
The University of Arizona
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| Department |
Physiology
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| Lab |
John Konhilas Lab
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| Street address |
1656 E. Mabel St.
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| City |
Tucson |
| State/province |
AZ |
| ZIP/Postal code |
85721 |
| Country |
USA |
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| Platforms (1) |
| GPL29562 |
Illumina NovaSeq 6000 (Sus scrofa domesticus) |
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| Samples (27)
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| GSM7113857 |
Pig 10, control/sham_BZ |
| GSM7113858 |
Pig 10, control/sham_IZ |
| GSM7113859 |
Pig 10, control/sham_RZ |
| GSM7113860 |
Pig 11, control/sham_BZ |
| GSM7113861 |
Pig 11, control/sham_IZ |
| GSM7113862 |
Pig 11, control/sham_RZ |
| GSM7113863 |
Pig 2, Myocardial infarction and HPAC treatment_BZ |
| GSM7113864 |
Pig 2, Myocardial infarction and HPAC treatment_IZ |
| GSM7113865 |
Pig 2, Myocardial infarction and HPAC treatment_RZ |
| GSM7113866 |
Pig 4, Myocardial infarction and HPAC treatment_BZ |
| GSM7113867 |
Pig 4, Myocardial infarction and HPAC treatment_IZ |
| GSM7113868 |
Pig 4, Myocardial infarction and HPAC treatment_RZ |
| GSM7113869 |
Pig 7, Myocardial infarction and HPAC treatment_BZ |
| GSM7113870 |
Pig 7, Myocardial infarction and HPAC treatment_IZ |
| GSM7113871 |
Pig 7, Myocardial infarction and HPAC treatment_RZ |
| GSM7113872 |
Pig 1, Myocardial infarction only_BZ |
| GSM7113873 |
Pig 1, Myocardial infarction only_IZ |
| GSM7113874 |
Pig 1, Myocardial infarction only_RZ |
| GSM7113875 |
Pig 5, Myocardial infarction only_BZ |
| GSM7113876 |
Pig 5, Myocardial infarction only_IZ |
| GSM7113877 |
Pig 5, Myocardial infarction only_RZ |
| GSM7113878 |
Pig 6, Myocardial infarction only_BZ |
| GSM7113879 |
Pig 6, Myocardial infarction only_IZ |
| GSM7113880 |
Pig 6, Myocardial infarction only_RZ |
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| Relations |
| BioProject |
PRJNA948031 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE228096_processed_data_files.tar.gz |
89.1 Mb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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