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

Cardiac lymphatic vessels are active regulators of immune surveillance and inflammatory resolution after myocardial injury. Intercellular adhesion molecule-1 (ICAM-1), a cell-surface glycoprotein broadly expressed in endothelial cells, mediates leukocyte adhesion and trafficking during inflammation; however, how Icam1 in lymphatic endothelial cells (LECs) shapes the post-infarction immune microenvironment remains unclear. In this study, an LEC-specific Icam1 conditional knockout ( Icam1cko) model was generated, and single-cell RNA sequencing and spatial transcriptomics were applied to characterize cellular and molecular remodeling at 3, 7, 21, and 42 days post-myocardial infarction (MI). Results showed that loss of Icam1 in LECs increased post-MI inflammation and fibrotic remodeling, indicating aggravated cardiac injury. Integrated transcriptomic analyses revealed broad alterations in cell composition and cell type-specific molecular signatures in the Icam1cko group, with prominent expansion and activation of proinflammatory neutrophil and macrophage subsets. Cell-cell communication analysis indicated that LEC-specific Icam1 deletion disrupted ICAM-dependent immune cell trafficking through lymphatic vessels, thereby impairing inflammatory cell clearance. Accumulated proinflammatory populations further reinforced leukocyte recruitment through CXCL-mediated crosstalk, amplifying immune imbalance within the infarcted myocardium. Collectively, these findings indicate that LEC Icam1 might be a potential therapeutic target for improving post-MI outcomes.