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 sequencing to evaluate the cellular dynamic features at 3-, 7-, 21-, and 42- days post-MI. Our results showed that Icam1 deletion increased inflammation and fibrosis, indicating aggravated cardiac damage. Our findings indicate that LEC Icam1 might be a potential therapeutic target for improving post-MI outcomes. We generated lymphatic-specific Icam1 conditional knockout (Icam1cko) model by crossing Icam1flox/flox with Prox1CreERT2 mice, and induced recombination by tamoxifen administration one week prior to MI. The cardiac tissue at 3-, 7-, 21-, and 42-days post-MI (dpMI) were harvested, and cell suspension was stained with PE Rat anti mouse CD31 (BD Pharmingen, 553373) or APC Rat anti mouse CD45 (BD Pharmingen, 559864), then followed incubated with anti-PE microbeads (MACS,130-105-639) or Anti-APC microbeads (MACS,130-090-855). Single cells from CD31+ or CD45+ cell populations were collected by FACS sorting for further analysis using single-cell RNA sequencing.