GSE140851 Direct comparison of mononucleated and binucleated cardiomyocytes reveals molecular mechanisms underlying distinct proliferative competencies

Contributors : Rebecca Windmueller ; Micheal P Morley ; Edward E MorriseySeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe mammalian heart is incapable of regenerating a sufficient number of cardiomyocytes to ameliorate the loss of contractile muscle after acute myocardial injury, often resulting in heart failure. Several reports have demonstrated that mononucleated (MoNuc) cardiomyocytes are more responsive to pro-proliferative stimuli than are binucleated (BiNuc) cardiomyocytes. However, techniques to isolate and characterize these two different cardiomyocyte populations have been lacking. We have developed a novel fluorescence associated cell sorting method to isolate highly enriched populations of MoNuc and BiNuc cardiomyocytes at various times of development. Transcriptome analysis reveals an underlying biological signature that defines the differences between MoNucs and BiNucs, including a central role for the E2f/Rb transcriptional network in establishing the divergent ability of these two populations to re-enter and complete the cell cycle. Moreover, inducing binucleation by genetically blocking the ability of cardiomyocytes to complete cytokinesis leads to a reduction in E2f target gene expression, linking the E2f pathway with nucleation. These data identify key molecular differences between MoNuc and BiNuc mammalian cardiomyocytes that can be used to leverage cardiomyocyte proliferation for promoting injury repair in the hear...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research

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Following left ventricular assist device (LVAD) mechanical unloading significant improvements in myocardial structure and function have been reported in some advanced heart failure (HF) patients, termed as Responders (R). Our prior work demonstrated a post-LVAD mismatch of glycolysis and oxidative phosphorylation characterized by upregulation of glycolysis without subsequent increase in pyruvate oxidation via the Krebs cycle. We hypothesized that the accumulated glycolytic intermediates are channeled into cardioprotective and repair pathways, such as the pentose phosphate pathway (PPP) and one-carbon metabolism (OCM), whic...
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: (318) Source Type: research
Significant tricuspid regurgitation (TR) in patients undergoing durable left ventricular assist device (LVAD) implantation has been associated with increased incidence of right heart failure (RHF). There is great surgical practice variability related to moderate TR repair at the time of LVAD implantation. In this single-center study, we investigated whether moderate TR repair concurrent with LVAD implantation has impact on late RHF occurrence.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: (1125) Source Type: research
Secondary mitral regurgitation (MR), not amenable to percutaneous or surgical repair, is common in advanced heart failure patients considered for LVAD implantation. Single center analyses have suggested variable frequency of persistent MR after LVAD implantation and consequent pulmonary hypertension, worse right heart function and more readmissions. The contemporary impact of newer devices such as the HeartMate 3 (HM3) on amelioration of MR post-LVAD implant remains uncertain. In this analysis of the MOMENTUM 3 pivotal trial and its Continued Access Protocol (CAP) study, we propose to assess the burden of significant resid...
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: (262) Source Type: research
Publication date: April 2020Source: JACC: Heart Failure, Volume 8, Issue 4Author(s): Wayne Batchelor, JoAnn Lindenfeld
Source: JACC: Heart Failure - Category: Cardiology Source Type: research
Publication date: April 2020Source: JACC: Heart Failure, Volume 8, Issue 4Author(s): Mathias Orban, Karl-Philipp Rommel, Edwin C. Ho, Matthias Unterhuber, Alberto Pozzoli, Kim A. Connelly, Simon Deseive, Christian Besler, Geraldine Ong, Daniel Braun, Jeremy Edwards, Mizuki Miura, Gökhan Gülmez, Lukas Stolz, Mara Gavazzoni, Michel Zuber, Martin Orban, Michael Nabauer, Francesco Maisano, Holger Thiele
Source: JACC: Heart Failure - Category: Cardiology Source Type: research
AbstractAimsThe PREPARE ‐MVR study (PRediction of Early PostoperAtive Right vEntricular failure in Mitral Valve repair (MVR) and to explore the associations between/Repair patients) sought to investigate the alterations of right ventricular (RV) contraction pattern in patients undergoing mitral valve replacement/repair ( MVR) and to explore the associations between pre‐operative RV mechanics and early post‐operative RV dysfunction (RVD).Methods and resultsWe prospectively enrolled 42 patients (63  ± 11 years, 69% men) undergoing open‐heart MVR. Transthoracic three‐dimensional (3D) echocardio...
Source: ESC Heart Failure - Category: Cardiology Authors: Tags: Original Research Article Source Type: research
Abstract Ischemic heart disease is a predominant cause of death worldwide. The loss or death of cardiomyocytes due to restricted blood flow often results in a cardiac injury. These injured cardiomyocytes are replaced by myofibroblasts that preserve structural integrity. However, the depleted cardiomyocytes lead to cardiac dysfunction such as pathological cardiac dilation, reduced cardiac contraction and fibrosis. Repair and regeneration of myocardium are the best possible therapy for the end-stage heart failure patients because the current therapies that can help restore the lost cardiomyocytes are limited to hear...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
Abstract We studied the experience of a 69-year-old woman with acute decompensated heart failure due to post-infarction ventricular septal rupture. She received mechanical hemodynamic support by Impella 2.5 (Abiomed, Danvers, MA, USA), percutaneous axial-flow left ventricular assist device, which improved intra-cardiac pressure, maintaining end-organ function. She was successfully bridged to the scheduled surgical repair of ventricular septal rupture following the 9-day Impella support and discharged on foot on the 32nd day. Impella might be a useful mechanical circulatory support device as a bridge tool to the scheduled...
Source: Journal of Artificial Organs - Category: Transplant Surgery Source Type: research
European Journal of Heart Failure, EarlyView.
Source: European Journal of Heart Failure - Category: Cardiology Authors: Tags: Editorial Comment Source Type: research
Abstract Interest in percutaneous mitral valve repair has increased during recent years. This is mainly driven by the significant number of patients being declined for mitral valve surgery because of a high risk of surgery-related complications or death. In this subset of patients, percutaneous edge-to-edge repair using the MitraClip device (Abbott, Menlo Park, CA, USA) has become an established treatment option, proven to be safe, efficient and associated with improved functional status. In contrast to primary mitral regurgitation (MR), clinical outcomes after mitral valve surgery appear to be less favourabl...
Source: Netherlands Heart Journal - Category: Cardiology Authors: Tags: Neth Heart J Source Type: research
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