Single-cell RNA sequencing of Versican (Vcan) knockout mice after cardiac ischemia.
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB61792 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Renal ischemia reperfusion in conditional HDAC2 knockout mice
| PRJNA543120 | ENA
Project description:Calpain 1 and 2 (CPN1/2) are calcium-dependent cysteine proteases that exist in cytosol and mitochondria. Pharmacologic inhibition of CPN1/2 decreases cardiac injury during ischemia (ISC) – reperfusion (REP) by improving mitochondrial function. However, the protein targets of CPN1/2 activation during ISC-REP are unclear. CPN1/2 include a large subunit and a small regulatory subunit 1 (CPNS1). Genetic deletion of the CPNS1 eliminates the activities of both CPN1 and CPN2. Conditional, cardiomyocyte specific CPNS1 knockout (KO) mice were used in the present study to clarify the role of CPN1/2 activation in mitochondrial damage during ISC-REP with an emphasis on identifying the potential protein targets of CPN1/2. Isolated hearts from wild type (WT) or CPNS1 KO mice underwent 25 min in vitro global ISC and 30 min REP. LDH activity in coronary effluent was measured to reflect cardiac injury. Mitochondria were isolated from the hearts. Cardiac injury was decreased in CPNS1 KO mice following ISC-REP compared to WT. ISC-REP decreased the rate of oxidative phosphorylation in WT but not in CPNS1 KO mice when glutamate + malate was used as complex I substrate. KO of CPNS1 led to a smaller decrease in CRC (calcium retention capacity) following REP compared to WT. The H2O2 generation was decreased in KO mitochondria following ISC-REP compared to WT. KO of CPNS1 also resulted in less cytochrome c release from mitochondria. Proteomic analysis of the isolated mitochondria showed that KO of CPNS1 increased the abundance of ribosomal proteins and mitochondrial biogenesis proteins. These results show that activation of CPN1/2 increases cardiac injury during ischemia-reperfusion by damaging mitochondria.
2021-12-21 | PXD022689 | Pride
Project description:Single-cell RNA sequencing of Hyaluronan Mediated Motility Receptor (Hmmr) overexpressing mice after cardiac ischemia.
| PRJEB61287 | ENA
Project description:This RNA-sequencing was performed to determine the differentially expressed mRNA after inhibition of Hmbox1 in cardiac ischemia/reperfusion injury
2024-05-17 | GSE241079 | GEO
Project description:The purpose of this study was to investigate the hypothesis that cardiomyocyte-specific loss of the electrogenic NBCe1 Na+-HCO3- cotransporter is cardioprotective during in vivo ischemia-reperfusion (IR) injury. An NBCe1 (Slc4a4 gene) cardiac conditional knockout mouse (KO) model was prepared by gene targeting. Cardiovascular performance of wild-type (WT) and cardiac-specific NBCe1 KO mice was analyzed by intraventricular pressure measurements, and changes in cardiac gene expression were determined by RNA Seq analysis. Response to in vivo I/R injury was analyzed after 30 minutes occlusion of the left anterior descending artery followed by 3 hours of reperfusion. Loss of NBCe1 in cardiac myocytes did not impair cardiac contractility or relaxation and caused only limited changes in gene expression patterns, such as those for electrical excitability. However, following ischemia and reperfusion, KO heart sections exhibited significantly fewer apoptotic nuclei than WT sections. These studies indicate that cardiac-specific loss of NBCe1 does not impair cardiovascular performance, causes only minimal changes in gene expression patterns, and protects against I/R injury in vivo.
2018-06-12 | GSE115579 | GEO
Project description:Immune cell infiltration in response to myocyte death contributes to extracellular matrix (ECM) remodeling and scar formation after myocardial infarction (MI). Caspase-recruitment domain protein 9 (CARD9) which belongs to CARD family acts as an adapter that mediate the transduction of proinflammatory signaling cascades in innate immunity. To investigate the role of CARD9 in cardiac injury and repair post ischemia, we subjected Card9 knockout mice to myocardial infarction (MI) , and then performed RNA-seq and gene expression profiling analysis using the ischemic cardiac tissues at 3 days post-MI, to identify key genes and pathways regulated by CARD9.
2023-10-25 | GSE235257 | GEO
Project description:Background: Extracellular matrix remodeling mechanisms are understudied in cardiac development and congenital heart defects. Two similar matrix-degrading metalloproteases, ADAMTS1 and ADAMTS5, are extensively co-expressed during mouse cardiac development. The mouse mutants of each have mild cardiac anomalies, but their combined genetic inactivation is precluded by tight linkage. We coupled Adamts1 inactivation with pharmacologic ADAMTS5 blockade to uncover stage-specific cooperative roles and mechanisms in mouse cardiac development. Methods: ADAMTS5 blockade was achieved in Adamts1 null mouse embryos using an activity-blocking monoclonal antibody during distinct developmental windows covering myocardial compaction or cardiac septation and outflow tract rotation. Synchrotron imaging, RNA in situ hybridization, immunofluorescence microscopy and electron microscopy were used to determine the impact on cardiac development and compared to Gpc6 and ADAMTS-cleavage resistant mouse mutants. Mass spectrometry-based N-terminomics was used to identify relevant substrates. Results: Combined inactivation of ADAMTS1 and ADAMTS5 prior to 12.5 days of gestation led to dramatic accumulation of versican-rich cardiac jelly and inhibited formation of compact and trabecular myocardium, which we also observed in mice with ADAMTS cleavage-resistant versican. Subsequently, combined knockout impaired outflow tract development and ventricular septal closure, generating a tetralogy of Fallot-like defect independently of versican proteolysis. N-terminomics of combined ADAMTS knockout and wild-type hearts identified a cleaved glypican-6 peptide only in the wild-type and showed that ADAMTS1 and ADAMTS5 each cleaved glypican-6. Paradoxically, ADAMTS1 and ADAMTS5 inactivated hearts lacked glypican-6 despite unaltered Gpc6 transcription. Gpc6-/- mice demonstrated similar rotational defects as the combined ADAMTS knockout and both had reduced Hedgehog signaling. Conclusions: ADAMTS1 and ADAMTS5 ensure proper cardiac development via cleavage of distinct proteoglycans, each with independent roles in cardiac development. Whereas versican clearance in cardiac jelly is required for proper ventricular cardiomyogenesis, glypican-6 cleavage may activate/stabilize this cell-surface proteoglycan which is required for Hedgehog signaling during outflow tract development.
2025-05-06 | PXD045706 | Pride
Project description:This study was a part of a larger study assessing the response of young pigs to cardiac ischemia/reperfusion (IR) injury. A mild cardiac injury approach (IR) was used in post-weaned pigs (1-month), to assess regenerative repair in young large mammals after transient ischemic injury. Female and male postnatal day (P)30 pigs were subjected to cardiac ischemia (1-hour) by occlusion of the left anterior descending artery followed by reperfusion (IR), or to sham operation. In pigs subjected to IR, myocardial damage occurred, indicated by increased circulating cardiac troponin I 2-hours post-ischemia. In addition, cardiac ejection fraction (EF) was significantly decreased 2-hours post-ischemia and reduced EF was maintained to the 4-week study end-point. Histology demonstrated evidence of CM cell cycling at 2-months of age in multinucleated CMs in both sham-operated and IR pigs. Following IR, regional scar formation and inflammation in the epicardial region proximal to injury were observed 4-weeks post-IR. Sex differences in cardiac function and collagen deposition were found, highlighting the importance of representing both sexes in cardiac injury studies. Together, our results describe an effective novel cardiac injury model in 1-month old swine, at a time when CM are still cycling. However, pigs subjected to IR show a prolonged decrease in cardiac function, and the formation of a small, regional scar with increased inflammation. Together, these data demonstrate that 1-month old pigs do not regenerate myocardium, but form a scar, after transient IR injury.
2020-04-27 | GSE137293 | GEO
Project description:Background: Extracellular matrix remodeling mechanisms are understudied in cardiac development and congenital heart defects. Two similar matrix-degrading metalloproteases, ADAMTS1 and ADAMTS5, are extensively co-expressed during mouse cardiac development. The mouse mutants of each have mild cardiac anomalies, but their combined genetic inactivation is precluded by tight linkage. We coupled Adamts1 inactivation with pharmacologic ADAMTS5 blockade to uncover stage-specific cooperative roles and mechanisms in mouse cardiac development. Methods: ADAMTS5 blockade was achieved in Adamts1 null mouse embryos using an activity-blocking monoclonal antibody during distinct developmental windows covering myocardial compaction or cardiac septation and outflow tract rotation. Synchrotron imaging, RNA in situ hybridization, immunofluorescence microscopy and electron microscopy were used to determine the impact on cardiac development and compared to Gpc6 and ADAMTS-cleavage resistant mouse mutants. Mass spectrometry-based N-terminomics was used to identify relevant substrates. Results: Combined inactivation of ADAMTS1 and ADAMTS5 prior to 12.5 days of gestation led to dramatic accumulation of versican-rich cardiac jelly and inhibited formation of compact and trabecular myocardium, which we also observed in mice with ADAMTS cleavage-resistant versican. Subsequently, combined knockout impaired outflow tract development and ventricular septal closure, generating a tetralogy of Fallot-like defect independently of versican proteolysis. N-terminomics of combined ADAMTS knockout and wild-type hearts identified a cleaved glypican-6 peptide only in the wild-type and showed that ADAMTS1 and ADAMTS5 each cleaved glypican-6. Paradoxically, ADAMTS1 and ADAMTS5 inactivated hearts lacked glypican-6 despite unaltered Gpc6 transcription. Gpc6-/- mice demonstrated similar rotational defects as the combined ADAMTS knockout and both had reduced Hedgehog signaling. Conclusions: ADAMTS1 and ADAMTS5 ensure proper cardiac development via cleavage of distinct proteoglycans, each with independent roles in cardiac development. Whereas versican clearance in cardiac jelly is required for proper ventricular cardiomyogenesis, glypican-6 cleavage may activate/stabilize this cell-surface proteoglycan which is required for Hedgehog signaling during outflow tract development.
2025-05-06 | PXD045868 | Pride
Project description:Data used in the publication: Analysis of cardiac ischemia-reperfusion injury using DIA proteomics and N-terminomics reveals alterations in mitochondrial function and metabolism
| MSV000092906 | MassIVE