Epicardial Placement of Human Placental Membrane Protects from Heart Injury in a Swine Model of Myocardial Infarction
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ABSTRACT:
PROVIDER: PRJNA948031 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23956037_1.fastq.gz | Fastqsanger.gz | |||
| SRR23956037_2.fastq.gz | Fastqsanger.gz | |||
| SRR23956038_1.fastq.gz | Fastqsanger.gz | |||
| SRR23956038_2.fastq.gz | Fastqsanger.gz | |||
| SRR23956039_1.fastq.gz | Fastqsanger.gz |
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Project description: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.
2023-05-30 | GSE228096 | GEO
Project description:Cardiac ischemic reperfusion injury (IRI) is paradoxically instigated by reestablishing 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. Using a clinically relevant model of IRI, swine were subjected to 45 min 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 nonischemic, ischemic, and border zone biopsies. Our results established HPAC limited the extent of cardiac injury by 50% (11.0 ± 2.0% vs. 22.0 ± 3.0%, 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 antiapoptotic and anti-inflammatory responses were measured in HPAC-treated biopsies. We provide quantitative evidence HPAC reduced cardiac injury from MI in a preclinical swine model, establishing a potential new therapeutic strategy for IRI. Minimizing the impact of MI remains a central clinical challenge. We present a new strategy to attenuate post-MI cardiac injury using HPAC in a swine model of IRI. Placement of HPAC membrane on the heart following MI minimizes ischemic damage, preserves cardiac function, and promotes anti-inflammatory signaling pathways.
| S-EPMC10582231 | biostudies-literature
Project description:Ischemic heart disease remains the leading cause of mortality and morbidity worldwide despite improved possibilities in medical care. Alongside interventional therapies, such as coronary artery bypass grafting (CABG), adjuvant tissue-engineered and cell-based treatments can provide regenerative improvement. Unfortunately, most of these advanced approaches require multiple lengthy and costly preparation stages without in turn delivering significant clinical benefit.
Here, we investigated the effect of epicardial matrix patch-encased atrial appendage micrografts (AAMs) in a mouse model of myocardial infarction. The matrix-covered AAM patches salvaged the myocardium from infarction-induced functional tissue loss. Fibrosis was attenuated, and site-targeted proteomics revealed AAM patch-activated pathways for angiogenesis and cardiogenesis. The matrix component of the graft further supports functional myocardial recovery by ventricular unloading.
The composite epicardial matrix graft encasing AAM micrografts delivers effects desirable for adjuvant cardiac therapy preserving functional cardiac tissue and restricting fibrosis after myocardial infarction.
2019-07-23 | MSV000084120 | MassIVE
Project description:The epicardium has a vital role in cardiac development, regeneration, injury, repair, and clinical prognosis, but it is unclear how the epicardium initiates the repair process during an acute myocardial infarction (MI). The objective of this study was to collect epicardial exudate in the early stages of acute MI by optimizing the active hydraulic ventricular through attaching a support system (ASD) and performing a proteomic analysis (proteomics). In order to develop a new pathological method, we need to monitor the real-time molecular changes associated with the epicardium in cardiac diseases and identify new potential therapeutic targets. The results showed the Microporous suction cup-like ASD system as a "second body chamber" that could better collect epicardial exudate from acute MI in rats, and the analysis of differentially expressed proteins (DEPs) in the samples showed that the DEPs within 6 hours of acute MI were mainly involved in the production of precursor metabolites and energy regulation of intracellular proteins, regulation of neuronal projection development, hippocampal signaling pathway, and other processes. In addition, we also found that the levels of acute inflammatory response and complement response in epicardial exudate were decreased, which may be related to the negative regulation of inflammation. In conclusion, the Microporous suction cup-like ASD system provides a new and precise means to study the molecular pathology of cardiovascular diseases (CVD): a collection of samples from the epicardium in situ and their analysis by multiple means in vitro. Through this process, we monitored the progress of the molecular pathology of CVD in real-time, elucidated the regulatory network of epicardial repair, and achieved cardiac repair by regulating the regenerative potential of the epicardium.
2022-03-05 | PXD032091 |
Project description:[Candida] sp. (uncertain placement) Genome sequencing
| PRJNA860074 | ENA
Project description:The epicardium is a mesothelial layer covering the myocardium and contributes to different cardiac lineage descendants during cardiogenesis. Fine-tuned balanced signaling defines epicardial specification and regulates cell plasticity and cell-fate decisions of epicardial-derived cells (EPCDs) by epicardial-to-mesenchymal transition (EMT). However, powerful tools to investigate epicardial cell function, including markers with pivotal roles in developmental signaling, are still lacking. Here, we recapitulated embryonic epicardiogenesis using human induced pluripotent stem cells (hiPSCs) and identified type II classical cadherin CDH18 as a novel biomarker defining lineage specification in human developing epicardium. The loss of CDH18 led to the onset of EMT and specific differentiation towards cardiac smooth muscle cells. Furthermore, GATA4 regulated epicardial CDH18 expression. These results demonstrate the production and enrichment of hiPSC-derived epicardial cells via the tracing of CDH18 expression, providing a model for investigating epicardial function in human development and disease and enabling new possibilities for regenerative medicine.
2022-02-18 | GSE165450 | GEO
Project description:Rationale: Epicardium-derived cells (EPDC) are formed in response to myocardial infarction and recapitulate an embryonic program that is likely to participate in cardiac regeneration and remodeling. The existence of atrial counterparts that are potentially involved in atrial remodeling is still elusive. Objective: We have elaborated and validated techniques for the robust isolation and cultivation of atrial and ventricular EPDC from the rat heart and compared their molecular phenotype with human atrial stromal cells obtained from tissue biopsies. Methods and Results: In vitro culture revealed that rat and human cells display a similar morphology, are highly enriched for the epicardial markers WT-1 and Tbx18 throughout in vitro expansion, strongly express the stem/progenitor cell markers CD73, CD90 and, surprisingly the early and late cardiac markers Gata4, Tbx5 and troponin T. In general, these cells display a similar molecular signature - which is different from human MSC - when analyzed by FACS, immunohistochemistry and real time PCR. We also examined the cell surface proteome of human and rat EPDC using cell surface biotinylation combined with nano-liquid chromatography - mass spectrometry. Proteome analysis revealed the presence of 149 overlapping proteins and >200 species specific proteins. These proteins are preferentially involved in cardiac repair and regeneration. Conclusions: This study demonstrates that atrial stromal cells are EPDC suggesting a common epicardial precursor. Cell surface proteome analysis suggests that atrial and ventricular EPDC are likely to play an important role during atrial and ventricular remodeling.
2018-10-19 | PXD005013 | Pride
Project description:Single cell RNA sequencing (scRNA-Seq) is applied to charaterize the pro-epicardial cells (proEpiCs) in mouse pro-epicardial organ (PEO).
2020-04-04 | GSE148040 | GEO
Project description:Background: Genome-wide detection of single feature polymorphisms (SFP) in swine using transcriptome profiling of day 25 placental RNA by contrasting probe intensities from either Meishan or an occidental composite breed with Affymetrix porcine microarrays is presented. A linear mixed model analysis was used to identify significant breed-by-probe interactions. Results: Gene specific linear mixed models were fit to each of the log2 transformed probe intensities on these arrays, using fixed effects for breed, probe, breed-by-probe interaction, and a random effect for array. After surveying the day 25 placental transcriptome, 789 probes with a q-value ≤ 0.05 and |fold change| ≥ 2 for the breed-by-probe interaction were identified as candidates containing SFP. To address the quality of the bioinformatics approach, universal pyrosequencing assays were designed from Affymetrix exemplar sequences to independently assess polymorphisms within a subset of probes. Of those probes sampled from high-, medium-, and low-ranking categories, 20 of 27 were confirmed by pyrosequencing to contain SFPs. In most cases, the 25-mer probe sequence printed on the microarray diverged from Meishan, not occidental crosses. This analysis was used to define a set of highly reliable predicted SFPs according to their probability scores. Conclusions: By this method we detected transition and transversion single nucleotide polymorphisms, as well as insertions/deletions. These results demonstrate that this approach can identify polymorphisms between two breeds and/or lines of any species for which a short oligonucleotide array is available, and can be used to rapidly develop markers for genetic mapping and association analysis in species where high density genotyping platforms are otherwise unavailable. SNPs and INDELS discovered by this approach have been publicly deposited in NCBI’s SNP repository dbSNP. This method is an attractive bioinformatics tool for uncovering breed-by-probe interactions, for rapidly identifying expressed SNPs, for investigating potential functional correlations between gene expression and breed polymorphisms, and is robust enough to be used on any Affymetrix gene expression platform. Keywords: Transcriptional profiling of Day 25 porcine placentas 30 samples: Breed (Meishan, Occidental) Placental Tissue, Days (25, 45, 65, 85, 105)
2009-02-05 | E-GEOD-10441 | biostudies-arrayexpress
Project description:Identification of epicardium-enriched genes in the embryonic heart. The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential for cardiac development and repair. Injury of the adult heart results in re-activation of a developmental gene program in the epicardium, but the transcriptional basis of epicardial gene expression has not been delineated. We established a mouse embryonic heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered on CCAAT/enhancer binding protein (C/EBP) transcription factors. Disruption of C/EBP signaling in the adult epicardium reduced injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial activation and heart injury, providing a platform for enhancing cardiac regeneration. Total RNA obtained from lacZ-positive epicardial cells isolated from the E11.5 Tcf21lacZ hearts compared to total dissociated heart cells
2012-11-01 | E-GEOD-41959 | biostudies-arrayexpress