Biology subjects

Zgierski-Johnston, C. M.

Publications and source records attributed to Zgierski-Johnston, C. M..

2 recordsLinked to original sources

bioRxiv2023

3D structure of fibroblasts and macrophages in the healthy and cryo-ablated heart

IntroductionCardiac non-myocytes (NM) play important roles in heart development, homeostasis, and lesion repair. To assess the relevance of different NM populations for cardiac (patho)physiology, a quantitative assessment of their abundance and structure in the different heart chambers is an essential prerequisite. We here present an experimental approach to determine the distribution, dimensions, and 3D morphology of fibroblasts (FB) and macrophages (M{Phi}) in healthy and pathologically remodelled hearts. Methods and resultsWe used Cre-loxP recombination to selectively target channelrhopsin-2 (ChR2)-eYFP to either FB or M{Phi} in healthy and cryo-ablated mouse hearts. Hearts were optically cleared using X-CLARITY and membrane-bound eYFP fluorescence was recorded by confocal microscopy. The resulting image stacks were segmented to generate 3D reconstructions of labelled cell populations in near native tissue. In doing so, we show that FB and M{Phi} have similar surface areas, volumes and morphologies, but that FB occupy larger fractional volumes than M{Phi} in all chambers of healthy murine hearts. Furthermore, M{Phi} appear primarily as single cells, whereas FB form extended networks of interconnected cells. In left-ventricular tissue following cryo-ablation, we observed large disordered networks of FB in the scar area with an increased volume occupied by FB both in the scar and remotely. In cryo-ablated ventricles, M{Phi} form comparatively small, but dense networks in the scar without changing their abundance in remote myocardium. ConclusionsOur study assesses the 3D distribution and structure of fluorescently labelled FB and M{Phi} in healthy and lesioned murine hearts. Based on 3D reconstructions of FB and M{Phi} networks, we quantified the surface areas and volumes of individual non-myocytes in the different chambers of the heart and in ventricular scar tissue, thus providing important quantitative data serving as basis for computational modelling of non-myocyte contributions to cardiac structure and physiology.

cell biology↗

bioRxiv2023

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

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 O_FIG O_LINKSMALLFIG WIDTH=192 HEIGHT=200 SRC="FIGDIR/small/568538v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@11dbccdorg.highwire.dtl.DTLVardef@1563d75org.highwire.dtl.DTLVardef@dcda58org.highwire.dtl.DTLVardef@182e598_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗