Publications by authors named "Ienglam Lei"

Background: New postoperative atrial fibrillation (POAF) occurs in about 40% after cardiac surgery. Mineralocorticoid receptor antagonists (MRA) are known to reduce chronic atrial fibrillation (AF) development and burden. We examined the impact of preoperative MRA use on POAF and also examine the atrial cell type impacted by MRA treatment during cold cardiac preservation.

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  • * Akt1 kinase activates this phosphorylation code, while protein phosphatase 2A inhibits it, suggesting a balance between activation and repression is crucial for iCM formation.
  • * Activation of PC14-3-3 disrupts inhibitory complexes within the nucleus that hinder cardiac gene expression, showcasing how post-translational modifications can influence cell reprogramming.
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  • Scientists found a special code called PC14-3-3 that helps turn regular cells into heart cells, which is super important for heart repair.
  • This code is controlled by two proteins: Akt1, which adds things to the code, and PP2A, which takes things away.
  • When the PC14-3-3 code is activated, it helps the heart cells form better by changing how other proteins are organized inside the cell.
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Cardiovascular disease (CVD) has become a severe threat to human health, with morbidity and mortality increasing yearly and gradually becoming younger. When the disease progresses to the middle and late stages, the loss of a large number of cardiomyocytes is irreparable to the body itself, and clinical drug therapy and mechanical support therapy cannot reverse the development of the disease. To explore the source of regenerated myocardium in model animals with the ability of heart regeneration through lineage tracing and other methods, and develop a new alternative therapy for CVDs, namely cell therapy.

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Ischemic cardiomyopathy (ICM) is a prominent form of heart failure, but the molecular mechanisms underlying ICM remain relatively understudied due to marked phenotypic heterogeneity. Alterations in post-translational modifications (PTMs) and isoform switches in sarcomeric proteins play important roles in cardiac pathophysiology. Thus, it is essential to define sarcomeric proteoform landscape to better understand ICM.

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Preservation quality of donor hearts is a key determinant of transplant success. Preservation duration beyond 4 hours is associated with primary graft dysfunction (PGD). Given transport time constraints, geographical limitations exist for donor-recipient matching, leading to donor heart underutilization.

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Primary graft dysfunction (PGD) remains the leading cause of early death following heart transplantation. Prolonged ischemic time during cold preservation is an important risk factor for PGD, and reliable evaluation of cardiac function is essential to study the functional responses of the donor heart after cold preservation. The accompanying video describes a technique to assess murine right and left ventricular function using ex vivo perfusion based in a Langendorff model after cold preservation for different durations.

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Functional mitral regurgitation (MR) in the setting of heart failure results from progressive dilatation of the left ventricle (LV) and mitral annulus. This leads to leaflet tethering with posterior displacement. Contrary to common assumptions, MR often does not resolve with LVAD decompression of the LV alone.

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Objectives: Unsupervised statistical determination of optimal allograft ischemic time (IT) on heart transplant outcomes among ABO donor heart types.

Methods: We identified 36,145 heart transplants (2000-2018) from the United Network for Organ Sharing database. Continuous and categorical variables were analyzed with parametric and nonparametric testing.

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Myocardial infarction (MI) is accompanied by severe energy deprivation and extensive epigenetic changes. However, how energy metabolism and chromatin modifications are interlinked during MI and heart repair has been poorly explored. Here, we examined the effect of different carbon sources that are involved in the major metabolic pathways of acetyl-CoA synthesis on myocardial infarction and found that elevation of acetyl-CoA by sodium octanoate (8C) significantly improved heart function in ischemia reperfusion (I/R) rats.

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Objectives: We examined for differences in pre-left ventricular assist device (LVAD) implantation myocardial transcriptome signatures among patients with different degrees of mitral regurgitation (MR).

Methods: Between January 2018 and October 2019, we collected left ventricular (LV) cores during durable LVAD implantation (n = 72). A retrospective chart review was performed.

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Aims: Aortic aneurysm and dissection (AAD) are high-risk cardiovascular diseases with no effective cure. Macrophages play an important role in the development of AAD. As succinate triggers inflammatory changes in macrophages, we investigated the significance of succinate in the pathogenesis of AAD and its clinical relevance.

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Background: Dysfunction and inflammation of hearts subjected to cold ischemic preservation may differ between left and right ventricles, suggesting distinct strategies for amelioration.

Methods And Results: Explanted murine hearts subjected to cold ischemia for 0, 4, or 8 h in preservation solution were assessed for function during 60 min of warm perfusion and then analyzed for cell death and inflammation by immunohistochemistry and western blotting and total RNA sequencing. Increased cold ischemic times led to greater left ventricle (LV) dysfunction compared to right ventricle (RV).

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Objective: Implantation of donor hearts with prolonged ischemic times is associated with worse survival. We sought to identify risk factors that modulate the effects of prolonged preservation.

Methods: Retrospective review of the United Network for Organ Sharing database (2000-2018) to identify transplants with >5 (n = 1526) or ≤5 h (n = 35,733) of donor heart preservation.

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Article Synopsis
  • The study investigated how the time an allograft heart is ischemic (not receiving blood) affects transplant outcomes, particularly focusing on different blood types.
  • It analyzed data from over 32,000 heart transplants and found that for hearts with ischemic time of 4 hours or more, those from O blood type donors had worse survival rates compared to other blood types.
  • The results indicated that longer ischemic times were linked to higher risks of death from primary graft dysfunction and chronic rejection, emphasizing the need for caution in choosing O donor hearts with extended ischemic time.
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  • Myocardial infarction, or heart attacks, are a leading cause of death and existing treatments do not effectively address the loss of heart muscle cells (cardiomyocytes) or help regenerate the heart.
  • A new invention involves a special copolymer that forms nanofibrous gelling microspheres (NF-GMS), which mimic the heart's natural extracellular matrix and can be injected to support heart cell transplantation.
  • In studies with rat models, injecting heart cells with NF-GMS significantly improved cell integration and cardiac recovery, demonstrating its potential for enhanced heart regeneration and applications in other biomedical fields.
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Background: Ischemic tolerance of donor hearts has a major impact on the efficiency in utilization and clinical outcomes. Molecular events during storage may influence the severity of ischemic injury.

Methods: RNA sequencing was used to study the transcriptional profile of the human left ventricle (LV, n=4) and right ventricle (RV, n=4) after 0, 4, and 8 hours of cold storage in histidine-tryptophan-ketoglutarate preservation solution.

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Dissecting epigenetic mechanisms controlling early cardiac differentiation will provide insights into heart regeneration and heart disease treatment. SWI/SNF complexes remodel nucleosomes to regulate gene expression and play a key role in organogenesis. Here, we reported a unique function of BAF250a in regulating the physical interaction of OCT4 and β-CATENIN during cardiac lineage differentiation from human ESCs.

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Background: Various solutions are used for donor heart preservation. We examined the outcomes in our heart transplant population where histidine-tryptophan-ketoglutarate (HTK) solution has been used for heart preservation since 2004.

Methods: This was a retrospective review of the United Network for Organ Sharing (UNOS) database (2004-2016) comparing our heart transplant outcomes with other national centers.

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Reprogramming of fibroblasts into induced cardiomyocytes (iCMs) is a potentially promising strategy for regenerating a damaged heart. However, low fibroblast-cardiomyocyte conversion rates remain a major challenge in this reprogramming. To this end, here we conducted a chemical screen and identified four agents, insulin-like growth factor-1, Mll1 inhibitor MM589, transforming growth factor-β inhibitor A83-01, and Bmi1 inhibitor PTC-209, termed IMAP, which coordinately enhanced reprogramming efficiency.

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Precise regulation of chromatin architecture is vital to physiological processes including hematopoiesis. ARID1A is a core component of the mammalian SWI/SNF complex, which is one of the ATP-dependent chromatin remodeling complexes. To uncover the role of ARID1A in hematopoietic development, we utilized hematopoietic cell-specific deletion of Arid1a in mice.

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