What the study found
The study found that diabetes-associated signaling involving TREM2, a receptor on mononuclear phagocytes, and endothelial cells is linked to impaired repair of ischemic blood vessels. The authors describe TREM2-endothelial cell interaction as a driver of diabetic vasculopathy.
Why the authors say this matters
The authors conclude that this interaction may be a potential therapeutic target in diabetes-associated peripheral arterial disease, a condition in which blood flow to the limbs is reduced. They also say their atlas of human diabetic vessels has translational relevance because it confirmed elevated endothelial-TREM2 signaling in human peripheral arterial disease, especially with diabetes.
What the researchers tested
The researchers used single-cell RNA sequencing and spatial transcriptomics to study human mesenteric arteries from non-diabetic donors and donors with type 2 diabetes. They also tested TREM2 inhibition and activation in cell experiments and in mouse models of diabetes with hindlimb ischemia, which is a model of peripheral arterial disease.
What worked and what didn't
The analysis identified TREM2 as one of the top type 2 diabetes-induced genes in mononuclear phagocytes, along with increased TREM2 ligands in endothelial cells. In vitro, TREM2 inhibition reduced proinflammatory responses in mononuclear phagocytes and endothelial cells and improved endothelial cell migration. In diabetic mice with hindlimb ischemia, TREM2 blockade improved perfusion recovery, while TREM2 activation worsened ischemic injury.
What to keep in mind
The abstract does not describe detailed study limitations. The main findings come from human artery profiling, cell experiments, and mouse models, so the results are presented within those studied systems.
Key points
- TREM2 was one of the top type 2 diabetes-induced genes in mononuclear phagocytes.
- Endothelial cells in diabetic vessels showed increased TREM2 ligands.
- TREM2 inhibition reduced proinflammatory responses and improved endothelial cell migration in vitro.
- In diabetic mouse models of hindlimb ischemia, TREM2 blockade improved perfusion recovery.
- TREM2 activation exacerbated ischemic injury in the mouse models.
- Human clinical samples showed elevated endothelial-TREM2 signaling in peripheral arterial disease, especially with diabetes.
Disclosure
- Research title:
- TREM2-endothelial signaling impairs ischemic vascular repair in diabetes
- Authors:
- Naseeb Kaur Malhi, Yingjun Luo, M. Chen, 汤小芳, Dongqiang Yuan, Rahuljeet Chadha, Alonso Tapia, Shufan Yin, Xuejing Liu, Meirigeng Qi, Marpadga A. Reddy, Jiawei Sun, James Otto, Lu Wei, John P. Cooke, Esak Lee, Rama Natarajan, Kevin W. Southerland, Zhen Bouman Chen
- Institutions:
- California Institute of Technology, City of Hope, City of Hope, City of Hope, City of Hope, City of Hope, City of Hope, City of Hope, City of Hope, City of Hope, City of Hope, City of Hope, City of Hope, City of Hope, Cornell University, Cornell University, Duke Medical Center, Duke Medical Center, Duke University, Duke University, Houston Methodist
- Publication date:
- 2026-04-22
- OpenAlex record:
- View
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