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Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery
Published on: August 16, 2019
Single-cell and spatial transcriptomic analyses reveal the dynamic transcript profiles of myocardial
Jiaqi He1,2, Dali Zhang2, Haixu Song2
1Graduate School, Army Medical University, Chongqing 400038, China.
Insights
This study reveals distinct subtypes of cardiac lymphatic endothelial cells (LECs) in infarcted hearts, each with unique roles in inflammation, injury, and edema resolution following myocardial infarction (MI). These findings highlight the functional diversity of LECs in cardiac repair.
Area of Science:
- Cardiovascular Biology
- Lymphatic System Research
- Regenerative Medicine
Background:
- Cardiac lymphatic endothelial cells (LECs) are crucial in myocardial edema and inflammation.
- The heterogeneity and specific functions of cardiac LECs remain largely unexplored.
Purpose of the Study:
- To investigate the heterogeneity and functional roles of cardiac lymphatic endothelial cells (LECs) post-myocardial infarction (MI).
- To map the spatial distribution and functional specialization of different LEC subtypes within the infarcted heart.
Main Methods:
- Integration of single-cell and spatial transcriptome data from mouse hearts after MI.
- Application of clustering, spatial localization, cell trajectory, and Cell-Chat analyses to identify LEC subtypes and functions.
Main Results:
- Identification of four distinct subtypes of cardiac LECs with specific spatial localizations and functions.
- LEC subtypes implicated in metabolic stress (LEC CaIII), immune response (LEC CaII), and edema resolution (LEC CaI, LEC collection).
- LEC-mediated regulation of myocardial edema via Aquaporin 1 and macrophage infiltration via galectin-9 (Gal-9)-CD44 pathway.
Conclusions:
- Cardiac LECs exhibit dynamic transcriptional heterogeneity and regional functional specialization post-MI.
- Distinct LEC functional subgroups contribute differently to myocardial tissue repair and pathology.
- Understanding LEC heterogeneity offers insights into therapeutic strategies for cardiac injury.
Background:
Cardiac lymphatics play an important role in myocardial edema and inflammation, however, the heterogeneity of cardiac lymphatic endothelial cells (LECs) and their biological functions have rarely been investigated.
Methods:
This study integrated single-cell sequencing data and spatial transcriptome data from mouse heart tissue at different time points post-myocardial infarction (MI), and then revealed LECs heterogeneity and biological functions by clustering, spatial localization, cell trajectory, and Cell-Chat analyses.
Results:
Four transcriptionally distinct subtypes of LECs were identified and localized in space. Cardiac LEC subgroups were found to be localized in different zones of infarcted heart related to different functions. LEC capillary III (LEC CaIII) may be involved in the direct regulation of myocardial injuries in an infarcted zone (IZ) from the perspective of metabolic stress, while LEC CaII may be related to the rapid immune inflammatory responses of the border zone (BZ) in the early stage of MI. LEC CaI, as well as LEC collection mainly participate in the regulation of myocardial tissue edema resolution in the middle and late stages post-MI. Cell trajectory and Cell-Chat analyses further identified that LECs may regulate myocardial edema through Aquaporin 1, and might affect the infiltration of macrophages through the galectin-9 (Gal-9)-CD44 pathway.
Conclusion:
This study revealed the dynamic transcriptional heterogeneity distribution of LECs in different regions of the infarcted heart, and these LECs formed different functional subgroups that might exhibit different bioeffects in myocardial tissue post-MI.

