Modulation of post-ischemic remodeling by an acellular hydrogel injection
Ontology highlight
ABSTRACT:
ORGANISM(S): Ovis aries
PROVIDER: GSE164245 | GEO | 2021/01/05
REPOSITORIES: GEO
Similar Datasets
Project description:Modulation of post-ischemic remodeling by an acellular hydrogel injection
| PRJNA689617 | ENA
Project description:Adverse mechanical cues promote pathological remodeling of ischemic left ventricle, which leads to heart failure and mortality in ischemic cardiomyopathy (ICM) patients. Intramyocardial injection of hydrogels reduces the mechanical stress in left ventricular (LV) wall, thus preserves cardiac function and geometry. The therapeutic concept has been tested in clinical trials and presented exciting potential. However, the theory of intramyocardial hydrogel injection still needs to be improved as the molecular biological connection between the mechanical effect and therapeutic outcomes is weak, and it is difficult to clearly separate the contribution of hydrogel mechanical support from physiological reaction to hydrogel chemistry and combinational surgical procedures in previous clinical translation studies. In this study, we transendocardially injected alginate hydrogel via a percutaneous coronary intervention in 10 ICM patients with end-stage heart failure. Thirty days after injection, cardiac function was improved, and LV size was reduced. Stress in the myocardium decreased as evaluated by finite element analysis. Similar mechanical and functional effects by hydrogel injections were observed in rat myocardial infarction (MI) model. Bulk and single-cell RNA sequencing revealed restoration in transcription levels of mechanosensing, cardiac contraction genes and other important pathways, which was mainly attributed to changes in cardiomyocytes. Such effects were not observed in rats receiving diluted hydrogel, confirming that mechanical effect instead of material chemistry is the main contributor. The resemblance in transcriptomic profile and the effect of hydrogel injection on mechanical stress and remodeling of LV wall between ICM patients and diseased rats indicated the applicability of the major mechanistic conclusions in rat model to human.
2024-08-01 | GSE253767 | GEO
Project description:Adverse mechanical cues promote pathological remodeling of ischemic left ventricle, which leads to heart failure and mortality in ischemic cardiomyopathy (ICM) patients. Intramyocardial injection of hydrogels reduces the mechanical stress in left ventricular (LV) wall, thus preserves cardiac function and geometry. The therapeutic concept has been tested in clinical trials and presented exciting potential. However, the theory of intramyocardial hydrogel injection still needs to be improved as the molecular biological connection between the mechanical effect and therapeutic outcomes is weak, and it is difficult to clearly separate the contribution of hydrogel mechanical support from physiological reaction to hydrogel chemistry and combinational surgical procedures in previous clinical translation studies. In this study, we transendocardially injected alginate hydrogel via a percutaneous coronary intervention in 10 ICM patients with end-stage heart failure. Thirty days after injection, cardiac function was improved, and LV size was reduced. Stress in the myocardium decreased as evaluated by finite element analysis. Similar mechanical and functional effects by hydrogel injections were observed in rat myocardial infarction (MI) model. Bulk and single-cell RNA sequencing revealed restoration in transcription levels of mechanosensing, cardiac contraction genes and other important pathways, which was mainly attributed to changes in cardiomyocytes. Such effects were not observed in rats receiving diluted hydrogel, confirming that mechanical effect instead of material chemistry is the main contributor. The resemblance in transcriptomic profile and the effect of hydrogel injection on mechanical stress and remodeling of LV wall between ICM patients and diseased rats indicated the applicability of the major mechanistic conclusions in rat model to human.
2024-08-01 | GSE253763 | GEO
Project description:Background MicroRNAs are potent regulators of biology and disease. The miR-15 family has been shown to regulate cardiomyocyte proliferation and antimiR-based inhibition induces a cardioprotective effect after myocardial infarction in mice. However, systemic delivery of antimiRs leads to accumulation in kidneys and liver, with relatively poor cardiac exposure. pH-responsive injectable hydrogels serve as a sustained-release drug delivery depot and could potentially be used to improve cardiac efficacy of antimiR therapeutics. Objective Examine whether hydrogel can improve local delivery of antimiR-195 in ischemic hearts to increase cardiac efficacy and limit off-target effects. Methods Study the effect of intramyocardial injections of hydrogel-formulated antimiR-195 under both baseline conditions and after ischemic injury. Results Intracardiac injections of UPy-PEG induced a transient inflammatory response that was no longer present 7 days post-injection. In vitro experiments showed that antimiR-195 was released from the gel, and induced microRNA inhibition leading to downstream cardiomyocyte proliferation. In vivo, intramyocardial delivery of antimiR-195 in UPy-PEG enhanced cardiac target de-repression compared to PBS-dissolved antimiR-195, despite a low cardiac retention. After ischemic injury, this translated into a greater therapeutic effect by increasing both target de-repression and cardiomyocyte proliferation. Conclusions UPy-PEG can be used as a cardiac delivery vehicle of antimiRs and intramyocardial injection of UPy-PEG formulated antimiR-195 is sufficient to improve cardiac efficacy of antimiR-195. Follow up experiments in large animals will enable us to assess the true added value of using UPy-PEG to increase cardiac exposure of antimiR therapies.
2022-11-19 | GSE140644 | GEO
Project description:This project deals with the characterisation and establishment of the baseline circulating acellular proteome of sheep serum using generic methods. Serum is a readily available substrate for most experimental and clinical applications as evidenced in recent sheep studies. It involves sample preparation for the optimisation of proteomic profiling of sheep serum. The chapter therefore represents the first step in the development of a proteomics pipeline for the detection protein alterations by first establishing the normal proteomic profile of sheep serum.
2017-06-19 | PXD004989 | Pride
Project description:Background MicroRNAs are potent regulators of biology and disease. The miR-15 family has been shown to regulate cardiomyocyte proliferation and antimiR-based inhibition induces a cardioprotective effect after myocardial infarction in mice. However, systemic delivery of antimiRs leads to accumulation in kidneys and liver, with relatively poor cardiac exposure. pH-responsive injectable hydrogels serve as a sustained-release drug delivery depot and could potentially be used to improve cardiac efficacy of antimiR therapeutics. Objective Examine whether hydrogel can improve local delivery of antimiR-195 in ischemic hearts to increase cardiac efficacy and limit off-target effects. Methods Study the effect of intramyocardial injections of hydrogel-formulated antimiR-195 under both baseline conditions and after ischemic injury. Results Intracardiac injections of UPy-PEG induced a transient inflammatory response that was no longer present 7 days post-injection. In vitro experiments showed that antimiR-195 was released from the gel, and induced microRNA inhibition leading to downstream cardiomyocyte proliferation. In vivo, intramyocardial delivery of antimiR-195 in UPy-PEG enhanced cardiac target de-repression compared to PBS-dissolved antimiR-195, despite a low cardiac retention. After ischemic injury, this translated into a greater therapeutic effect by increasing both target de-repression and cardiomyocyte proliferation. Conclusions UPy-PEG can be used as a cardiac delivery vehicle of antimiRs and intramyocardial injection of UPy-PEG formulated antimiR-195 is sufficient to improve cardiac efficacy of antimiR-195. Follow up experiments in large animals will enable us to assess the true added value of using UPy-PEG to increase cardiac exposure of antimiR therapies.
2022-11-19 | GSE140660 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-08-01 | GSE253768 | GEO
Project description:Purpose: rHCI hydrogel injection improves cardiac function within 2 days of treatment in a mouse model of myocardial infarction. The goal of this study was to determine the differences in gene expression with rHCI hydrogel injection post-myocardial infarction. Methods: Total RNA was isolated from left ventricle tissue of samples and mRNA stranded libraries were prepared and sequenced in Illumina NovaSeq 6000 with a depth of 50 million reads per sample. Differential expression analysis of aligned reads was done to compared gene expression between PBS vs. rHCI, PBS vs. sham, and rHCI vs. sham comparisons. Results: Differentially expressed genes between sham and PBS as well as rHCI and PBS showed known gene signatures of myocardial infarction. Seven differentially expressed genes were detected with rHCI hydrogel injection compared to PBS. Conclusions: The target gene ERDR1 that is downregulated with rHCI injection led to discovery of changes in cardiomyocyte apoptosis and reduction of oxidative stress adducts with rHCI injection post-myocardial infarction.
2023-08-31 | GSE182205 | GEO
Project description:DNA barcodes can be used to identify single cells in a sequencing data space while optical codes can be used to track single live cells in an image data space. We have developed dual image and DNA (ID)-coding, which identifies individual single cells in both live image and sequencing data spaces. Samples provided here are relevant to proof-of-concept studies of ID-coding presented in the associated publication. DNA barcoded micro-particles were encapsulated in hydrogel droplets with or without single cells. The hydrogel droplets were then subjected to “single-droplet sequencing” where whole polyA-bearing nucleic acid components within a hydrogel droplet (i.e. mRNA from cells and synthetic DNA on beads) were concatenated by the same cell barcodes.
2023-12-11 | E-MTAB-12988 | biostudies-arrayexpress
Project description:This dataset presents the results of protein sample preparation strategies for enriching a novel encyclopaedic peptide spectral library using the liquid fraction of sheep blood. The method used showed the capability of simultaneously detecting hundreds of key proteins in the liquid fraction of blood (circulating acellular proteome) using sheep as a model by: a) Prototyping of the circulating acellular proteome of healthy sheep using serum b) A comprehensive analysis of fractions of acetone precipitated sheep serum and plasma; c) A comprehensive analysis of fractions of partial organic precipitation of sheep serum and plasma proteins using acetonitrile; d) Combinatorial peptide ligand library protein enrichment of sheep serum and plasma; e) Off-gel fractionation of serum proteins; f) Extraction of protein data from ex-diagnostic sheep serum; g) Derivation of peptide data from serum and plasma of endotoxin treated sheep.
2022-11-15 | PXD005002 | Pride