Similar Datasets
Project description:Role of Endothelial and Mesenchymal cell transitions in heart failure and recovery thereafter
| PRJNA676178 | ENA
Project description:Recovery from Heart Failure: Microvascular Mechanisms
| PRJNA1066226 | ENA
Project description: Not available
| S-EPMC7874124 | biostudies-literature
Project description:Background: Heart failure (HF) is a significant global health problem. Left-ventricular assist device (LVAD) implantation serves as a bridge for patients awaiting heart transplantation. Intriguingly, LVAD support often improves cardiac histology and function, sometimes enough to avoid transplantation after LVAD removal. However, the cellular programs underlying this recovery remain unclear. Methods: Myocardial tissues were obtained from patients with HF at the time of LVAD implantation (pre-LVAD) and explantation (post-LVAD) for histological analysis and single-nucleus RNA sequencing (snRNA-seq). A murine model of HF recovery, combined with lineage tracing studies, was employed to define cellular sources of vascular repair. Cardiac function, fibrosis, and vascular density were assessed using echocardiography, histology, and fluorescent microsphere perfusion. A patient-derived cardiac non-myocyte culture system was established to interrogate mechanisms of cell-fate regulation. Results: Post-LVAD myocardial tissues exhibited reduced fibrosis and increased capillary density compared to pre-LVAD samples. Across samples, fibroblast abundance inversely correlated with endothelial cell abundance, consistent with enhanced angiogenesis during recovery. SnRNA-seq identified a fibroblast subset predisposed to undergo mesenchymal-to-endothelial transition, acquiring an endothelial cell identity. Additionally, non-myocytes from pre-LVAD hearts proliferated poorly and failed to form vascular structures, whereas non-myocytes from post-LVAD hearts displayed greater proliferative and angiogenic capacity, forming vessel-like structures, reinforcing the association of HF recovery with angiogenic reprogramming. Mechanistically, knockdown of c-Myc by siRNA shifted post-LVAD non-myocytes to a pre-LVAD-like state, while c-Myc overexpression by mRNA in pre-LVAD cells induced a post-LVAD-like phenotype, implicating c-Myc as one contributor to this fate switch. A model of heart failure recovery in mice mimicked the histological and functional changes in patients, with physiological evidence of increased microvascular perfusion, associated with a fibroblast-to-endothelial transition documented by lineage tracing. Conclusions: HF recovery involves reduced fibrosis and enhanced microvascularization, partly driven by fibroblast-to-endothelial cell fate transition. c-Myc functions as one regulator of this transition, offering a mechanistic entry point to develop regenerative therapies in HF.
2026-03-25 | GSE253535 | GEO
Project description:Recovery of cardiac function is the ultimate goal of heart failure therapy yet is infrequently observed and remains poorly understood. Here we characterize the cellular landscape and predictors of cardiac recovery by performing single nucleus RNA-sequencing (snRNA-seq) from 40 heart failure patients who recovered LV systolic function following left ventricular assist device (LVAD) implantation and patients who did not recover and non-diseased donors. We identify cell type specific transcriptional signatures of recovery in all cell types, most prominently in macrophages and fibroblasts. Pro-inflammatory macrophages and inflammatory signalling in fibroblasts were negative predictors of recovery, while downregulation of RUNX1 transcriptional activity in macrophages and fibroblasts was associated with recovery. In silico perturbation of RUNX1 in macrophages and fibroblasts recapitulated the transcriptional state of recovery. In a mouse model of cardiac recovery mediated by BRD4 inhibition, we observed a decrease in macrophage and fibroblast Runx1 expression, diminished chromatin accessibility within a Runx1 intronic peak, and acquisition of human recovery signatures. These findings suggest that cardiac recovery is a unique biological state and identify RUNX1 as a possible therapeutic target to facilitate cardiac recovery.
2023-02-28 | GSE226314 | GEO
Project description:Defining cardiac functional recovery in end-stage heart failure at single cell resolution
| PRJNA939636 | ENA
Project description:This experiment was designed to study the alteration in expression of mRNA is kidney following recovery from transient acute renal failure. The model used was a 52 min. bilateral renal artery clamping, followed by reperfusion, which resulted in a transient loss of renal function, followed by a functional recovery. All tissue in this study was harvested 35 days post-surgery, when renal function was restored, and renal structure largelyy normal. For controls, sham-operated animals were used. An N of 6 post-ischemia reperfusion animals were used with 6 sham-operated controls. For hybridization studies, RNA from one of six post-ischemic acute renal failure animals were compared with with RNA from kidney of six sham-operated control animals. Each ARF vs. sham-operated comparison was performed twice, alternating the cy3 and cy5 label between the two hybridizations for each pair. A second set of hybridizations was carried out using sham vs. sham hybridizations. This was done to get a quantitative analysis of the variation of the biological and microarry platform.
2010-06-10 | E-GEOD-1714 | biostudies-arrayexpress
Project description: Not available
| S-EPMC9852013 | biostudies-literature
Project description:This experiment was designed to study the alteration in expression of mRNA is kidney following recovery from transient acute renal failure. The model used was a 52 min. bilateral renal artery clamping, followed by reperfusion, which resulted in a transient loss of renal function, followed by a functional recovery. All tissue in this study was harvested 35 days post-surgery, when renal function was restored, and renal structure largelyy normal. For controls, sham-operated animals were used. An N of 6 post-ischemia reperfusion animals were used with 6 sham-operated controls. For hybridization studies, RNA from one of six post-ischemic acute renal failure animals were compared with with RNA from kidney of six sham-operated control animals. Each ARF vs. sham-operated comparison was performed twice, alternating the cy3 and cy5 label between the two hybridizations for each pair. A second set of hybridizations was carried out using sham vs. sham hybridizations. This was done to get a quantitative analysis of the variation of the biological and microarry platform. Keywords: parallel sample
2005-01-26 | GSE1714 | GEO