Integrated Transcriptomic Analysis Revealed Lymphatic-mediated Immune Dynamics after Myocardial Infarction

Cardiac lymphatic vessels actively regulate immune responses after injury. Intercellular cell adhesion molecule-1 (ICAM-1), a cell surface glycoprotein, extensively expresses in endothelial cells and participates in inflammatory processes by regulating leukocyte recruitment from circulation. However, the specific role of lymphatic endothelial cells (LECs) Icam1 in regulating the immune microenvironment associated with myocardial infarction (MI) remains elusive. In this study, we generated an LEC-specific Icam1 conditional knockout (cko) model and performed single-cell RNA and spatial transcriptome sequencing to evaluate the cellular dynamic features at 3-, 7-, 21-, and 42- days post-MI. Our results showed that the deletion of Icam1 in LECs led to increased inflammation and fibrosis, indicating aggravated cardiac damage. We identified alterations in cell type-specific proportions and molecular signatures in Icam1cko group. Notably, the activation of neutrophil and macrophage subsets with pro-inflammatory properties are key features in Icam1cko group. Cellular interaction analysis revealed that Icam1 knockout might obstruct immune cell drainage via LEC-specific ICAM signaling. Additionally, accumulated pro-inflammatory cell populations further attracted immune cells via CXCL crosstalk, resulting in the further destruction of immune microenvironment in Icam1cko hearts. Collectively, our findings indicate that LEC Icam1 might be a potential therapeutic target for improving post-MI outcomes.