Key result
Transgenic HCM mouse hearts show chamber-specific pathological lymphatic alterations, particularly in the right atrium.
Why the study?
Three-dimensional microscopy and quantitative image analysis methods were needed to study cardiac lymphatic vessel morphology and pathological remodeling in familial hypertrophic cardiomyopathy mouse hearts.
A novel 3D lightsheet microscopy workflow enables multi-scale quantitative analysis of pathological changes in cardiac lymphatic vessels in mouse models of hypertrophic cardiomyopathy.
Should not change clinical HCM management; leaves open whether lymphatic alterations contribute to progression in patients.
Objective Three‐dimensional (3D) microscopy and image data analysis are necessary for studying the morphology of cardiac lymphatic vessels (LyVs) and their association with other cell types. We aimed to develop a methodology for 3D multiplexed lightsheet microscopy and highly sensitive and quantitative image analysis to identify pathological remodeling in the 3D morphology of LyVs in young adult mouse hearts with familial hypertrophic cardiomyopathy (HCM). Methods We developed a 3D lightsheet microscopy workflow providing a quick turn‐around (as few as 5–6 days), multiplex fluorescence detection, and preservation of LyV structure and epitope markers. Hearts from non‐transgenic and transgenic (TG) HCM mice were arrested in diastole, retrograde perfused, immunolabeled, optically cleared, and imaged. We built an image‐processing pipeline to quantify LyV morphological parameters at the chamber and branch levels. Results Chamber‐specific pathological alterations of LyVs were identified, and significant changes were seen in the right atrium (RA). TG hearts had a higher volume percent of ER‐TR7 + fibroblasts and reticular fibers. In the RA, we found associations between ER‐TR7 + volume percent and both LyV segment density and median diameter. Conclusions This workflow and study enabled multi‐scale analysis of pathological changes in cardiac LyVs of young adult mice, inviting ideas for research on LyVs in cardiac disease.
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Phillips et al. (2023) studied familial hypertrophic cardiomyopathy (HCM). Transgenic HCM model vs. Non-transgenic mice was evaluated on Lymphatic vessel morphological parameters at the chamber and branch levels. Transgenic hypertrophic cardiomyopathy mouse hearts exhibited chamber-specific pathological alterations of lymphatic vessels, particularly in the right atrium, compared to non-transgenic controls.
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