Integrated transcriptomic analysis reveals lymphatic Icam1-mediated immune dynamics after myocardial infarction

Area of Science:

• Cardiovascular Biology
• Immunology
• Vascular Biology

Background:

• Cardiac lymphatic vessels regulate immune responses and inflammation resolution post-myocardial injury.
• Intercellular adhesion molecule-1 (ICAM-1) is key in leukocyte trafficking during inflammation.
• The role of ICAM-1 in lymphatic endothelial cells (LECs) post-myocardial infarction (MI) is not well understood.

Purpose of the Study:

• To investigate the function of ICAM-1 in LECs in the context of post-MI cardiac remodeling.
• To elucidate the impact of LEC-specific ICAM-1 deficiency on the cardiac immune microenvironment after MI.

Main Methods:

• Generated an LEC-specific ICAM-1 conditional knockout (cko) mouse model.
• Utilized single-cell RNA sequencing and spatial transcriptomics to analyze cardiac tissue at multiple time points post-MI.
• Performed cell-cell communication analysis to understand immune cell interactions.

Main Results:

• LEC-specific ICAM-1 deletion exacerbated post-MI inflammation and fibrotic remodeling, indicating aggravated cardiac injury.
• Transcriptomic analyses revealed significant alterations in cell composition, with expanded proinflammatory neutrophil and macrophage subsets.
• Deletion of ICAM-1 in LECs disrupted immune cell trafficking via lymphatic vessels, impairing inflammatory cell clearance and amplifying immune imbalance.

Conclusions:

• LEC ICAM-1 plays a critical role in regulating the immune microenvironment and tissue repair after myocardial infarction.
• Targeting LEC ICAM-1 presents a potential therapeutic strategy for improving outcomes following MI.