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Updated: Dec 23, 2025

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Published on: January 24, 2025
Diabetes mellitus impairs circulating proangiogenic granulocytes
Roberta Cappellari1,2, Marianna D'Anna1,2, Lisa Menegazzo1,2
1Veneto Institute of Molecular Medicine, Padova, Italy.
Diabetes impairs proangiogenic granulocytes (PAGs), crucial for blood vessel formation. Improving glucose control with dapagliflozin significantly increased PAG levels and function, suggesting a therapeutic target for diabetic cardiovascular risk.
Area of Science:
- Cardiovascular Research
- Immunology
- Endocrinology
Background:
- Cardiovascular disease risk is elevated in diabetes, partly due to impaired blood vessel formation (angiogenesis).
- Diabetes negatively impacts blood cells involved in angiogenesis, including proangiogenic granulocytes (PAGs).
Purpose of the Study:
- To investigate whether diabetes impairs the function and quantity of proangiogenic granulocytes (PAGs).
- To assess the impact of glucose control on PAGs in individuals with diabetes.
Main Methods:
- Characterized and quantified CD49d+ granulocytes (PAGs) in peripheral blood from type 1/2 diabetic and control participants.
- Assessed in vitro angiogenesis assays and PAG antigenic profiles.
- Quantified PAGs before and after treatment with dapagliflozin (SGLT2 inhibitor) and in diabetic mouse models.
Main Results:
- PAGs (eosinophils/neutrophils) express CD49d, CXCR4, and VEGFR1, supporting endothelial cell angiogenesis.
- Diabetic PAGs showed significantly reduced capacity to stimulate endothelial cell tubule formation and were reduced by 30-40%.
- PAG levels increased 1.8-fold after dapagliflozin treatment, correlating inversely with plasma glucose and HbA1c.
Conclusions:
- Diabetes significantly impairs proangiogenic granulocytes (PAGs), with hyperglycemia playing a direct role.
- These findings offer mechanistic insights into defective angiogenesis in diabetes.
- Restoration of PAG function may be a therapeutic strategy for managing diabetic cardiovascular complications.
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