Cellular Heterogeneity of the Heart

Michel, Nathaly Anto; Ljubojević-Holzer, Senka; Bugger, Heiko; Zirlik, Andreas

doi:10.3389/fcvm.2022.868466

Cited by 15 publications

(8 citation statements)

References 117 publications

(149 reference statements)

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“…However, while cells of the PNS are mononucleated, a large proportion of murine cardiomyocytes are binucleated [34]. Therefore, (i) the fraction of cardiac SC may be higher than reflected by our nucleus staining [35], and (ii) this scaling may differ between mice of different age if the share of multi-nucleated CM increases between the ages of 2-3 and 20-24 months. Additionally, due to the large intra-individual variability in cardiac nerve thickness (as opposed to sciatic nerves), we were unable to provide a quantification of cardiac aging-related dynamics in iCNS nerve cross-sectional area.…”

Section: Discussionmentioning

confidence: 99%

Age-related structural and functional changes of the intracardiac nervous system

Sassu,

Tumlinson,

Stefanovska

et al. 2023

Preprint

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BackgroundAlthough aging is known to be associated with an increased incidence of both atrial and ventricular arrhythmias, there is limited knowledge about how Schwann cells (SC) and the intracardiac nervous system (iCNS) remodel with age. Here we investigate the differences in cardiac SC, parasympathetic nerve fibers, and muscarinic acetylcholine receptor M2 (M2R) expression in young and old mice. Additionally, we examine age-related changes in cardiac responses to sympathomimetic and parasympathomimetic drugs.Methods and ResultsLower SC density, lower SC proliferation and fewer parasympathetic nerve fibers were observed in cardiac and, as a control sciatic nerves from old (20–24 months) compared to young mice (2–3 months). In old mice, CSPG4 was increased in sciatic but not cardiac nerves. Expression of M2R was lower in ventricular myocardium and ventricular conduction system from old mice compared to young mice, while no significant difference was seen in M2R expression in sino-atrial or atrio-ventricular node pacemaker tissue. Heart rate was slower and PQ intervals were longer in Langendorff-perfused hearts from old mice. Ventricular tachycardia and fibrillation were more frequently observed in response to carbachol administration in hearts from old mice versus those from young mice.ConclusionsOn the background of reduced presence of SC and parasympathetic nerve fibers, and of lower M2R expression in ventricular cardiomyocytes and conduction system of aged hearts, the propensity of ventricular arrhythmogenesis upon parasympathomimetic drug application is increased. Whether this is caused by an increase in heterogeneity of iCNS structure and function remains to be elucidated.Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Age-related structural and functional changes of the intracardiac nervous system

Sassu,

Tumlinson,

Stefanovska

et al. 2023

Preprint

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“…This unique yet overly complex morphology can obstruct many therapies directed specifically to only one cell type. The CMs, for example, that constitute most of the cell mass in reality account for only 30% of the total cell number in the heart [ 25 ]. Therefore, the therapeutic targeting of CMs for correction can be troublesome.…”

Section: Discussionmentioning

confidence: 99%

Selective Delivery to Cardiac Muscle Cells Using Cell-Specific Aptamers

Philippou,

Mastroyiannopoulos,

Tomazou

et al. 2023

Pharmaceuticals

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In vivo SELEX is an advanced adaptation of Systematic Evolution of Ligands by Exponential Enrichment (SELEX) that allows the development of aptamers capable of recognizing targets directly within their natural microenvironment. While this methodology ensures a higher translation potential for the selected aptamer, it does not select for aptamers that recognize specific cell types within a tissue. Such aptamers could potentially improve the development of drugs for several diseases, including neuromuscular disorders, by targeting solely the proteins involved in their pathogenesis. Here, we describe our attempt to utilize in vivo SELEX with a modification in the methodology that drives the selection of intravenously injected aptamers towards a specific cell type of interest. Our data suggest that the incorporation of a cell enrichment step can direct the in vivo localization of RNA aptamers into cardiomyocytes, the cardiac muscle cells, more readily over other cardiac cells. Given the crucial role of cardiomyocytes in the disease pathology in DMD cardiomyopathy and therapy, these aptamers hold great potential as drug delivery vehicles with cardiomyocyte selectivity.

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“…Cardiac progenitor/stromal cells (CPCs) represent a rare population with relevant potential to contribute to cardiogenesis during embryonic development, which becomes almost completely quiescent in adulthood. While the role of CPCs in actively contributing to cardiovascular lineages postnatally and following injury is currently a matter of debate [ 89 , 90 , 91 ], several lines of investigation have highlighted their relevant trophic paracrine effects [ 92 , 93 ]. Epicardium-derived progenitor cells (EPDCs) can release EVs enhancing the proliferation of neonatal murine cardiomyocytes in vitro.…”

Section: Defining the Optimal Source Of Evs For Future Cardiac Paracr...mentioning

confidence: 99%

Evolving Strategies for Extracellular Vesicles as Future Cardiac Therapeutics: From Macro- to Nano-Applications

Guerricchio,

Barile,

Bollini

2024

IJMS

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Cardiovascular disease represents the foremost cause of mortality and morbidity worldwide, with a steadily increasing incidence due to the growth of the ageing population. Cardiac dysfunction leading to heart failure may arise from acute myocardial infarction (MI) as well as inflammatory- and cancer-related chronic cardiomyopathy. Despite pharmacological progress, effective cardiac repair represents an unmet clinical need, with heart transplantation being the only option for end-stage heart failure. The functional profiling of the biological activity of extracellular vesicles (EVs) has recently attracted increasing interest in the field of translational research for cardiac regenerative medicine. The cardioprotective and cardioactive potential of human progenitor stem/cell-derived EVs has been reported in several preclinical studies, and EVs have been suggested as promising paracrine therapy candidates for future clinical translation. Nevertheless, some compelling aspects must be properly addressed, including optimizing delivery strategies to meet patient needs and enhancing targeting specificity to the cardiac tissue. Therefore, in this review, we will discuss the most relevant aspects of the therapeutic potential of EVs released by human progenitors for cardiovascular disease, with a specific focus on the strategies that have been recently implemented to improve myocardial targeting and administration routes.

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Cellular Heterogeneity of the Heart

Cited by 15 publications

References 117 publications

Age-related structural and functional changes of the intracardiac nervous system

Age-related structural and functional changes of the intracardiac nervous system

Selective Delivery to Cardiac Muscle Cells Using Cell-Specific Aptamers

Evolving Strategies for Extracellular Vesicles as Future Cardiac Therapeutics: From Macro- to Nano-Applications

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