Single-nucleus transcriptomic atlas of human pericoronary epicardial adipose tissue across different stages of coronary artery disease: a study on recurrent in-stent restenosis
Z F Song, M Yu, Z Yang, X L Zhou, J Yuan, W Feng, W YangAbstract
Background and Aims
Despite the widespread clinical application of second-generation stent balloons, recurrent in-stent restenosis (RISR) remains one of the major adverse events following percutaneous coronary intervention. Pericoronary epicardial adipose tissue (PCAT) surrounds the coronary arteries without any anatomic barrier. However, the cellular and molecular mechanisms between PCAT and recurrent restenosis in coronary arteries still remains unclear.
Method
We performed single-nucleus RNA sequencing on PCAT samples collected from 3 groups: 1) controls (patients with valvular disease requiring surgery, n=4), 2) stable coronary artery disease (CCS, patients undergoing coronary artery bypass grafting, CABG, n=5), and 3) recurrent in-stent restenosis (RISR, n=5) Comparative analyses were performed including cellular compositional analysis, cell-type resolved transcriptomic changes, gene coexpression network analysis, and intercellular communication analysis.
Results
Clustering of 165,329 nuclei revealed 12 distinct clusters, with adipocytes, monocytes/macrophages, preadipocytes, and T cells as the predominant cell types across all groups. BCL11Bhigh T cells were significantly expanded in the RISR group. Subpopulation analysis of smooth muscle cell (SMC) identified a SKAP1high SMC subset.Gene Ontology (GO) analysis indicated that this subset is involved in immune regulation and T cell activation, while KEGG pathway analysis suggested its role in signaling pathways related to T cell differentiation.
Conclusion
This study presents the first comprehensive transcriptomics map of PCAT in patients. SKAP1high VSMCs within PCAT may play an immunoregulatory role in modulating T cell activation and expansion. Targeting these cells might present promising novel strategies for RISR.Transcriptomic landscape in RISRFor image description, please refer to the figure legend and surrounding text.