Cationic proteins from eosinophils bind bone morphogenetic protein receptors promoting vascular calcification and atherogenesis
Authors' conclusion
Eosinophils release cationic proteins that can promote SMC calcification and atherogenesis using the BMPR-1A/1B-Smad-1/5/8-Runx2 signalling pathway.
Study context
- Population
- Human and mouse atherosclerotic lesions, vascular smooth muscle cell (SMC); men from the Danish Cardiovascular Screening trialsubpopulation of 394
- Participants
- 5,864 participants
Main finding
As reported in the abstract
- Eosinophil accumulation in human and mouse atherosclerotic lesions
- Eosinophil deficiency (ΔdblGATA mice) slowed atherogenesis, increased lesion SMC content and reduced calcification; protection muted by donor eosinophils (wild-type (WT), Il4-/-, Il13-/-) or mEar1
- Eosinophils or mEar1, but not IL4 or IL13, increased calcification of WT SMC but not Runx2 knockout SMC
- Eosinophils and mEar1 activated Smad-1/5/8, without affecting Smad-2/3 activation or BMPR-1A/1B/2 or TGFBR1/2 expression
- mEar1 formed immune complexes with BMPR-1A/1B but not TGFBR1/2, and bound BMPR-1A and BMPR-1B with similar affinity
- Human eosinophil cationic protein (ECP) and EDN bound BMPR-1A/1B on human vascular SMC and promoted SMC osteogenic differentiation
- Blood eosinophil counts and ECP levels correlated with calcification scores of arterial segments from coronary to iliac arteries
Original publication
Cationic proteins from eosinophils bind bone morphogenetic protein receptors promoting vascular calcification and atherogenesis. Eur Heart J. Published 3 June 2023. doi:10.
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