Delving into unique MASH-endothelial cells through a single-cell lens: From mechanisms to novel therapeutic targets

We read with great interest the recent article published in your journal, entitled "Delineating unique MASH-endothelial cells in metabolic dysfunction-associated steatotic liver disease using single-cell lensing" [ 1 ].This study precisely defines unique endothelial cell subpopulations in metabolic dysfunction-associated steatohepatitis(MASH) using single-cell technology, providing valuable data for understanding the heterogeneity and functional shifts of liver endothelial cells during disease progression.It represents a significant advancement in the field of liver vascular biology.The authors successfully elucidated the transformation of liver sinusoidal endothelial cells (LSECs) towards a pro-inflammatory phenotype (i.e., endothelial dysfunction) in the context of MASH.We particularly commend the researchers' integrated pathway analysis of the LSEC transcriptome and proteome, which clearly identified leukocyte transendothelial migration and focal adhesion formation as core pathways affected in MASH.This finding aligns closely with current focus in the field on the initial stages of hepatic inflammation.Based on the outstanding results of this study, we wish to extend the discussion concerning the underlying mechanisms and potential therapeutic targets involved, with a specific focus on whether a particular subtype of endothelial cells (ENDOs) may actively promote liver disease progression.What are the core drivers of the "unique MASH endothelial cell" phenotype identified in the study?Recent multi-omics research