Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes. Other studies suggest that new cardiomyocytes are born at a very low rate, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches--genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry--that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinucleation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548046 | PMC |
| http://dx.doi.org/10.1038/nature11682 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Growth Differentiation Factor 15 as a Marker for Chronic Ventricular Pacing.
J Clin Med
December 2024
Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria.
Right ventricular pacing is an effective and safe treatment option for patients experiencing symptomatic bradycardia. However, some individuals may develop left ventricular dysfunction as a consequence. Growth differentiation factor 15 (GDF-15), which is not present in a healthy adult heart, is upregulated in cardiomyocytes in response to various stress stimuli.
View Article and Find Full Text PDFInteractions between the developing heart and the embryonic immune system are essential for proper cardiac development and maintaining homeostasis, with disruptions linked to various diseases. While human pluripotent stem cell (hPSC)-derived organoids are valuable models for studying human organ function, they often lack critical tissue-resident immune cells. Here, we introduce an advanced human heart assembloid model, termed hHMA (human heart-macrophage assembloid), which fully integrates autologous cardiac tissue- resident macrophages (MPs) with pre-existing human heart organoids (hHOs).
View Article and Find Full Text PDFMetabolic engineering improves transduction efficiency and downstream vector isolation by altering the lipid composition of extracellular vesicle-enclosed AAV.
Metab Eng
December 2024
Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA. Electronic address:
Article Synopsis
- Adeno-associated viruses (AAV) are effective for gene therapy, but face challenges like pre-existing immunity in patients and low efficiency in certain cell types.
- This study uses a metabolic engineering method to enhance the production of extracellular vesicle-enclosed AAV (EV-AAV) by knocking out the PTDSS1 enzyme, resulting in a significantly higher yield and easier purification process.
- The engineered EV-AAV9 showed improved cell entry and successful gene delivery in mouse brains, indicating that lipid metabolic engineering could enhance gene therapy vectors' effectiveness and development.
Role of NLRP3 Inflammasome in Heart Failure Patients Undergoing Cardiac Surgery as a Potential Determinant of Postoperative Atrial Fibrillation and Remodeling: Is SGLT2 Cotransporter Inhibition an Alternative for Cardioprotection?
Antioxidants (Basel)
November 2024
Departamento de Cardiología, Clínica Alemana de Santiago, Santiago 7500922, Chile.
In heart failure (HF) patients undergoing cardiac surgery, an increased activity of mechanisms related to cardiac remodeling may determine a higher risk of postoperative atrial fibrillation (POAF). Given that atrial fibrillation (AF) has a negative impact on the course and management of HF, including the need for anticoagulation therapy, identifying the factors associated with AF occurrence after cardiac surgery is crucial for the prognosis of these patients. POAF is thought to occur when various clinical and biochemical triggers act on susceptible cardiac tissue (first hit), with oxidative stress and inflammation during cardiopulmonary bypass (CPB) surgery being potential contributing factors (second hit).
View Article and Find Full Text PDFQuantitative label-free digital holographic imaging of cardiomyocyte optical volume, nucleation, and cell division.
J Mol Cell Cardiol
November 2024
Department of Biological Sciences, San Jose State University, San Jose, CA 95192, USA. Electronic address:
Cardiac regeneration in newborn rodents depends on the ability of pre-existing cardiomyocytes to proliferate and divide. This capacity is lost within the first week of postnatal development when these cells rapidly switch from hyperplasia to hypertrophy, withdraw from the cell cycle, become binucleated, and increase in size. How these dynamic changes in cell size and nucleation impact cardiomyocyte proliferative potential is not well understood.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!