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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. Atherosclerosis and Vascular Medicine
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1510082

Single-cell and spatial analysis reveals the interaction between ITLN1 + foam cells and SPP1 + macrophages in atherosclerosis

Provisionally accepted
Ying Li Ying Li 1Shanshan Wang Shanshan Wang 2Ruidan Zhang Ruidan Zhang 1Yingying Gong Yingying Gong 3Yulu Che Yulu Che 4Zongfu Pan Zongfu Pan 3,5*
  • 1 College of Pharmacy, Zhejiang University of Technology, Hangzhou, China
  • 2 School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
  • 3 Center for Clinical Pharmacy, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Hangzhou, Jiangsu, China
  • 4 Hangzhou Medical College, Hangzhou, Zhejiang, China, 杭州市, China
  • 5 Zhejiang Key Laboratory of Head & Neck Cancer Translational Research, Hangzhou, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    Cardiovascular disease (CVD) caused by atherosclerosis (AS) remains the leading cause of mortality in developed countries. Investigation of cellular heterogeneity within the inflammatory microenvironment is crucial for advancing disease management strategies. In this study, we elucidate the regulatory function of distinct cell populations in AS pathogenesis. Correlation analysis identified a strong association between vascular smooth muscle cell (VSMC)-derived ITLN1+ foam cells and SPP1+FABP5+ macrophages. CellChat analysis revealed a robust intercellular communication network between these two populations, mediated primarily by the MIF-(CD74+CD44) and SPP1-CD44 ligand-receptor axis. Spatial transcriptomics further confirmed significant spatial physical interactions between ITLN1+ foam cells and SPP1+ FABP5+ macrophages, highlighting their coordinated role in lipid accumulation within AS plaques. These findings shed light on the mechanisms driving AS onset and progression and propose potential immunotherapeutic strategies targeting this intercellular crosstalk for AS treatment.

    Keywords: Atherosclerosis, macrophage, VSMC, Foam Cells, crosstalk

    Received: 12 Oct 2024; Accepted: 29 Jan 2025.

    Copyright: © 2025 Li, Wang, Zhang, Gong, Che and Pan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zongfu Pan, Center for Clinical Pharmacy, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Hangzhou, 310014, Jiangsu, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.