CDK1 inhibition reduces osteogenesis in endothelial cells in vascular calcification.

Yan Zhao, Yang Yang, Xiuju Wu, Li Zhang, Xinjiang Cai, Jaden Ji, Sydney Chen, Abigail Vera, Kristina I Boström, Yucheng Yao

JCI insight 2024 Mar 08

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Vascular calcification is a severe complication of cardiovascular diseases. Previous studies demonstrated that endothelial lineage cells transitioned into osteoblast-like cells and contributed to vascular calcification. Here, we found that inhibition of cyclin-dependent kinase (CDK) prevented endothelial lineage cells from transitioning to osteoblast-like cells and reduced vascular calcification. We identified a robust induction of CDK1 in endothelial cells (ECs) in calcified arteries and showed that EC-specific gene deletion of CDK1 decreased the calcification. We found that limiting CDK1 induced E-twenty-six specific sequence variant 2 (ETV2), which was responsible for blocking endothelial lineage cells from undergoing osteoblast differentiation. We also found that inhibition of CDK1 reduced vascular calcification in a diabetic mouse model. Together, the results highlight the importance of CDK1 suppression and suggest CDK1 inhibition as a potential option for treating vascular calcification.

Citation

Yan Zhao, Yang Yang, Xiuju Wu, Li Zhang, Xinjiang Cai, Jaden Ji, Sydney Chen, Abigail Vera, Kristina I Boström, Yucheng Yao. CDK1 inhibition reduces osteogenesis in endothelial cells in vascular calcification. JCI insight. 2024 Mar 08;9(5)