Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Temporal inhibition of ADAM17 in fibroblasts reduces stiffness and promotes vascularization following myocardial infarction

ABSTRACT: Myocardial infarction (MI) triggers a complex remodelling process that leads to heat failure if uncontrolled. A Disintegrin and metalloproteinase-17 (ADAM17), a transmembrane sheddase, is upregulated in patients with ischemic cardiomyopathy, colocalized to myofibroblasts (myoFB) in the infarct tissues. Fibroblasts are key players in post-MI scar formation and exist in different states with diverse functions. Using mice with inducible Adam17 deletion in homeostatic FBs (Adam17 FB-KD ), or activated FBs (Adam17 myoFB-KD ), we found that ADAM17 loss in homeostatic FBs impaired infarct formation post-MI and increased mortality due to left ventricular (LV) rupture. Conversely, ADAM17 loss in myoFBs limited infarct expansion, LV dilation and dysfunction up to 4 weeks post-MI. Ex vivo and in vitro experiments revealed that the beneficial effects in Adam17 myoFB-KD mice are due to reduced stiffness of the infarct tissue through suppressing activation of EGFR-YAP-pathway, which promoted vascularization and thereby limited infarct expansion. Pharmacological inhibition of ADAM17 prior to MI was ineffective, but short-term ADAM17 inhibition after MI by targeting myoFBs significantly alleviated the adverse LV remodeling and dysfunction with beneficial effects up to 4wks post-MI. Our study identifies a short-term therapeutic window for ADAM17 inhibition to prevent long-term adverse remodeling, dysfunction and heart failure post-MI.

ORGANISM(S): Mus musculus

PROVIDER: GSE306012 | GEO | 2026/07/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Global fibroblast activation in the left ventricle but localized fibrosis after myocardial infarction

Project description:Copper coated stent were implanted into the LAD coronary artery of porcine animal weighing between 20-25 kg, which leads to a severe coronary stenosis and myocardial infarct (MI). After MI, Fb are activated throughout the LV, presumably through TGF-β1 in response to increased wall stress and/or inflammation. Additional regional specific signaling leads to interstitial fibrosis via collagen cross-linking in MIadjacent. Local LOX activity could be stimulated by higher mechanical load imposed by tethering to the infarct or signals could diffuse from the scar.Identifying specific signaling cues to maintain the mature state of MyoFb phenotype in the scar tissue may open new perspectives in targeting the MyoFb reversibility in interstitial fibrosis without damaging existing scar tissue.

2017-10-31 | GSE98504 | GEO

Expression data from C57BL/6J and MRL/MpJ hearts following acute myocardial infarction

Project description:The Murphy Roth Large (MRL) mouse, a strain capable of regenerating right ventricular myocardium, has a high post-myocardial infarction (MI) survival rate compared with C57BL6/J (C57) mice. The biological processes responsible for this survival advantage are unknown. We compared acute post-MI gene expression in C57 and MRL hearts using microarrays and identified promising candidate biological processes underlying increased survival in the MRL. Hearts from both strains were excised at different time points before or after MI for RNA extraction and hybridization to MOE430A arrays. Baseline hearts were excised from healthy mice that had not undergone the MI procedure (day 0). Infarct tissue in this case means tissue taken from the anterior-apical region that would be the infarct region in a post-MI heart. Non-infarct covers the remainder of the LV. Post-MI hearts were excised either 1 or 5 days after MI. We had successful hybridizations for 3 replicates each of C57 day 0 infarct and non-infarct tissue (6 arrays), 4 MRL day 0 infarct and non-infarct tissue (8 arrays), 4 C57 day 1 infarct and non-infarct tissue (8 arrays), 4 MRL day 1 infarct and non-infarct tissue (8 arrays), 4 C57 day 5 infarct and non-infarct tissue (8 arrays), and 4 MRL day 5 infarct and non-infarct tissue (8 arrays).

2010-05-27 | E-GEOD-19322 | biostudies-arrayexpress

Gene expression profiling in porcine chronic myocardial ischemia treated with intramyocardial injections of secretome

Project description:Closed-chest reperfused MI was induced in pigs by 90-min occlusion, followed by reperfusion of the mid LAD (day 0) and by cardiac MRI with late enhancement (LE) at day 3. At day 30 the animals received either porcine APOSEC (n=8) or placebo medium (n=8) in a randomized manner, injected into the border zone of MI using 3D NOGA percutaneous intramyocardial guidance. At day 60, control cardiac MRI with LE and measurements of myocardial viability via diagnostic NOGA were performed. Gene expression profiling of the infarct core, border zone and normal myocardium was performed using microarray analysis, confirmed by quantitative real-time PCR. Percutaneous endomyocardial injections of APOSEC led to a significant (p<0.05) decrease in infarct size and in improvement of cardiac index and myocardial viability compared to medium treatment. Trend towards higher LV ejection fraction was observed in APOSEC vs. the Medium placebo group (45.4M-BM-15.9% vs 37.4M-BM-18.9%, p=0.052). Transcriptome analysis revealed significant downregulation of caspase-1 and other inflammatory genes in the APOSEC-affected areas. PCR showed higher expression of myogenic factor, Mefc2 (p<0.05) gene with downregulated caspase-3 (p<0.05) in the APOSEC-pigs. We have investigated the effects of catheter-based endomyocardial injections of APOSEC (secretome of apoptotic peripheral white blood cells) on porcine chronic post-infarction (MI) left ventricular (LV) dysfunction and gene expression profile. Pigs randomized to receive eithersecretome (n=8) or medium (placebo control, n=8)

2013-12-31 | E-GEOD-47397 | biostudies-arrayexpress

Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial Infarction

Project description:Background. Accumulation of extracellular matrix in the myocardium attenuates cardiac contractile function, and predisposes to arrhythmias and sudden cardiac death. Connective tissue growth factor (CTGF) is a matricellular protein that has been shown to promote development of cardiac fibrosis. Objectives. To investigate for the potential of CTGF monoclonal antibody (CTGF mAb) in protecting from development of cardiac fibrosis following myocardial infarction (MI), and to evaluate its effect during infarct repair and acute cardiac ischemia-reperfusion (I/R) injury. Methods. Mice were subjected to MI or to I/R injury and treated with either control IgG or CTGF mAb. Cultured human cardiac fibroblasts were used to investigate the signalling mechanisms modulated by CTGF mAb. Results. Treatment with CTGF mAb for four days from day three after MI improved survival, attenuated infarct expansion, and resulted in better preserved left ventricular (LV) systolic function. CTGF mAb therapy for six weeks from day seven after MI reduced the MI-induced increase in cardiomyocyte size, heart weight to body weight ratio and remote LV fibrosis. RNA sequencing analysis of LV samples showed that CTGF mAb induced expression of cardiac repair/developmental genes and normalized the MI-induced increase in expression of inflammatory/profibrotic genes. CTGF mAb induced c-Jun N-terminal kinase (JNK) phosphorylation in vivo and in vitro, and inhibition of JNK abrogated the reduced collagen production in CTGF mAb treated fibroblasts. Conclusions. Treatment with CTGF mAb induces expression of cardiac repair/developmental genes and inhibits expression of inflammatory/pro-fibrotic genes in MI hearts providing benefit during post-MI cardiac repair and reducing post-MI cardiac fibrosis.

2019-04-02 | GSE129134 | GEO

Gene expression profiling in porcine chronic myocardial ischemia treated with intramyocardial injections of secretome

Project description:Closed-chest reperfused MI was induced in pigs by 90-min occlusion, followed by reperfusion of the mid LAD (day 0) and by cardiac MRI with late enhancement (LE) at day 3. At day 30 the animals received either porcine APOSEC (n=8) or placebo medium (n=8) in a randomized manner, injected into the border zone of MI using 3D NOGA percutaneous intramyocardial guidance. At day 60, control cardiac MRI with LE and measurements of myocardial viability via diagnostic NOGA were performed. Gene expression profiling of the infarct core, border zone and normal myocardium was performed using microarray analysis, confirmed by quantitative real-time PCR. Percutaneous endomyocardial injections of APOSEC led to a significant (p<0.05) decrease in infarct size and in improvement of cardiac index and myocardial viability compared to medium treatment. Trend towards higher LV ejection fraction was observed in APOSEC vs. the Medium placebo group (45.4±5.9% vs 37.4±8.9%, p=0.052). Transcriptome analysis revealed significant downregulation of caspase-1 and other inflammatory genes in the APOSEC-affected areas. PCR showed higher expression of myogenic factor, Mefc2 (p<0.05) gene with downregulated caspase-3 (p<0.05) in the APOSEC-pigs. We have investigated the effects of catheter-based endomyocardial injections of APOSEC (secretome of apoptotic peripheral white blood cells) on porcine chronic post-infarction (MI) left ventricular (LV) dysfunction and gene expression profile.

2013-12-31 | GSE47397 | GEO

Transcriptomic profiling of chronic infarcted pig hearts

Project description:Myocardial infarction (MI) is the leading cause for hear failure (HF). Following MI, the non-infarcted region of left ventricle (LV) is critical for maintaining heart function, and disruption of the LV contributes greatly to post-MI HF. Transcriptomic profiling by high-throughput sequencing was performed in a chronic HF pig model, to explore the molecular changes in the post-MI LV related to cardiovascular deterioration. Samples were taken from heart tissue of MI-induced pigs and from control pigs not subjected to MI. Regions of the heart where samples were taken included the site of ischemia (LV ischemia), area bordering ischemia (LV border), area remote to ischemia (LV remote) and the right ventricle (RV).

2021-10-04 | E-MTAB-8856 | biostudies-arrayexpress

Transcriptional profiling of left ventricle and peripheral blood cells in rats with post-myocardial infarction

Project description:Myocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. In this study, we performed transcriptional profiling of LVs in rats with a wide range of experimentally induced infarct sizes and of peripheral blood mononuclear cells (PBMCs) in animals that developed HF. We used microarrays to investigate gene expression in the left ventricle (LV) accompanying myocardial infarction and concomitant heart failure (HF) in a well validated model of post-infarcted heart failure and to evaluate their reflection in peripheral blood mononuclear cells (PBMCs) Myocardial infarction (MI) was induced in male Wistar rats by ligation of the proximal left coronary artery. The sham-operated group (control group) was subjected to the same protocol, except that the suture was not tied around the proximal left coronary artery. Sham-operated rats (n=6) and rats with small (n=6), moderate (n=6), and large (n=5) MI size were included into the experiment two months after the operation. Then, left ventricules and blood samples were obtained for RNA extraction and hybridization on Affymetrix microarrays. Microarrays were used to compare the LV and PBMCs transcriptomes of control and experimental animals. The development of heart failure was estimated by echocardiography and catheterization.

2013-11-15 | E-GEOD-47495 | biostudies-arrayexpress

Transcriptional profiling of left ventricle and peripheral blood cells in rats with post-myocardial infarction

2013-11-15 | GSE47495 | GEO

Bone marrow macrophage derived GPNMB protein binds to orphan receptor GPR39 and plays a critical role in cardiac repair

Project description:Levels of Glyco Protein Non-metastatic Melanoma protein B (GPNMB), a type I transmembrane protein, originally identified in non-metastatic melanomas has been shown to be strongly associated with human heart failure. However, the role of GPNMB in modulation of cardiac injury and cardiac function remains unclear. We analyzed human cardiac global gene expression data sets and observed increased GPNMB expression in failing hearts. In murine hearts after myocardial infarction (MI), we showed that GPNMB expression increased by an order of magnitude. Lineage tracing and bone marrow transplantation experiments demonstrated that bone marrow macrophages were the primary source of GPNMB in the injured heart. Using genetic loss of function approaches, we demonstrate that animals deficient in GPNMB exhibited significantly higher mortality, cardiac rupture and developed rapid post infarct LV dysfunction. Conversely gain of function approaches by increasing circulating GPNMB levels by viral delivery led to augmentation of post MI heart function. Single cell transcriptomics demonstrated pleiotropic effects of GPNMB on gene expression of myocytes and non-myocytes leading to enhanced myocyte contraction and decreased fibroblast activation. Using chemical cross-linking studies and immunoprecipitation studies, we identified the orphan receptor GPR39 as a receptor for circulating GPNMB. In animals deficient in GPR39, GPNMB failed to deliver beneficial effects on post infarct heart function. Taken together, these observations demonstrate that bone marrow macrophage derived GPNMB plays a pivotal role in cardiac repair following myocardial infarction, by mediating its pleiotropic effects in part via the orphan receptor GPR39

2024-09-17 | GSE277086 | GEO

Single-nucleus RNA sequencing Resolves Microenvironmental Dynamics in Brown/Beige Adipose Tissue after Bariatric Surgery

Project description:Obesity, a chronic disease marked by pathological adipose expansion, drives systemic comorbidities such as type 2 diabetes, cardiovascular disease, and cancer, severely impairing quality of life. Bariatric surgery remains the most effective intervention for sustained weight loss and metabolic improvement, yet the mechanisms underlying adipose tissue remodeling post-surgery remain poorly understood. Using single-cell RNA sequencing, we generated high-resolution transcriptional maps of murine brown adipose tissue (BAT) and beige adipose tissue pre- and post-bariatric surgery, uncovering dynamic microenvironmental shifts. Following surgery, both BAT and beige adipose tissues displayed a notable expansion of myofibroblast (myoFB) populations and a parallel reduction in adipocytes (AP). Cell communication analysis via CellChat revealed enhanced AP-myoFB crosstalk mediated by IGF1 signaling activation, alongside suppression of VEGF pathway interactions between AP and endothelial cells (EC). Pseudotemporal trajectory analysis identified an AP subpopulation (AP6) enriched in fibrosis-associated genes (Zbtb16, Fkbp5) that progressively upregulated 11 genes during differentiation toward myoFB. Spatial correlation analysis further demonstrated co-localization of these genes with Igf1r in myoFBs. Collectively, this work delineates surgery-induced microenvironmental reprogramming in thermogenic adipose depots and proposes a novel mechanism whereby 11 potential transition regulators synergize with IGF1 signaling to drive AP6-myofibroblast transdifferentiation.

2026-02-18 | GSE307599 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data