Diabetes-induced TREM2–endothelial cell signaling impairs ischemic vascular repair
MPs exhibited foam cell-like features but acquired a proinflammatory gene profile in DM. Functionally, TREM2 inhibition in vitro attenuated proinflammatory responses in MPs and ECs and enhanced EC migration. In streptozotocin- and high-fat high-sucrose diet-induced mouse models of diabetes with hindlimb ischemia (a model of PAD), TREM2 blockade using a neutralizing antibody improved perfusion recovery, whereas TREM2 activation with an agonist exacerbated ischemic injury. Analysis of clinical samples confirmed elevated EC-TREM2 signaling in human PAD, particularly in the setting of DM, highlighting its translational relevance. Collectively, our study presents an atlas of human diabetic vessels with single-cell and spatial resolution, identifying TREM2-EC interaction as a driver of diabetic vasculopathy and a potential therapeutic target in DM-associated PAD.
Authors
- Esak Lee (ORCID: https://orcid.org/0000-0002-5328-6677)
- Alonso Tapia (ORCID: https://orcid.org/0000-0002-3123-9159)
- Yingjun Luo (ORCID: https://orcid.org/0000-0003-2271-3725)
- 汤小芳
- Meirigeng Qi (ORCID: https://orcid.org/0000-0002-8531-8733)
- Shufan Yin
- John P. Cooke (ORCID: https://orcid.org/0000-0003-0033-9138)
- Rama Natarajan (ORCID: https://orcid.org/0000-0003-4494-1788)
- Dongqiang Yuan
- James Otto (ORCID: https://orcid.org/0000-0002-4552-1171)
- Rahuljeet Chadha (ORCID: https://orcid.org/0000-0002-3805-6144)
- Naseeb Kaur Malhi (ORCID: https://orcid.org/0000-0002-8981-2974)
- Kevin W. Southerland (ORCID: https://orcid.org/0000-0002-0306-2130)
- Marpadga A. Reddy (ORCID: https://orcid.org/0000-0001-9259-7243)
- Lu Wei (ORCID: https://orcid.org/0000-0001-9170-2283)
- M. Chen
- Zhen Bouman Chen
- Xuejing Liu (ORCID: https://orcid.org/0000-0002-3931-0191)
- Jiawei Sun
Institutions
- California Institute of Technology (US)
- Houston Methodist (US)
- Duke University (US)
- Cornell University (US)
- City of Hope (US)
- Duke Medical Center (US)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2026-04-22
- DOI
- https://doi.org/10.1126/scitranslmed.adu3761
- Citations
- 1
- Primary Topic
- Inflammation biomarkers and pathways
- Type
- article
- Field-Weighted Citation Impact
- 13.41
Funders
- American Heart Association
- National Institutes of Health
- Institut Kanser Negara