CDK1 inhibition reduces osteogenesis in endothelial cells in vascular calcification

Yan Zhao1, Yang Yang1, Xiuju Wu1

  • 1Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

JCI Insight
|March 8, 2024
PubMed

Insights

Inhibition of cyclin-dependent kinase 1 (CDK1) prevents endothelial cells from becoming bone-like cells, reducing vascular calcification. This discovery offers a potential new treatment for vascular calcification.

Area of Science:

  • Cardiovascular Biology
  • Cell Biology
  • Molecular Medicine

Background:

  • Vascular calcification is a significant complication of cardiovascular diseases.
  • Endothelial lineage cells can transform into osteoblast-like cells, contributing to vascular calcification.

Purpose of the Study:

  • To investigate the role of cyclin-dependent kinase (CDK) in endothelial cell transition and vascular calcification.
  • To explore CDK1 inhibition as a potential therapeutic strategy for vascular calcification.

Main Methods:

  • Examined endothelial cell (EC) to osteoblast-like cell transition.
  • Investigated the effect of CDK inhibition on vascular calcification in vitro and in a diabetic mouse model.
  • Analyzed the role of E-twenty-six specific sequence variant 2 (ETV2) in the process.

Main Results:

  • CDK inhibition prevented endothelial lineage cells from transitioning to osteoblast-like cells, reducing vascular calcification.
  • CDK1 was highly induced in ECs in calcified arteries, and its deletion decreased calcification.
  • Limiting CDK1 increased ETV2, which blocked osteoblast differentiation in endothelial cells.
  • CDK1 inhibition reduced vascular calcification in a diabetic mouse model.

Conclusions:

  • CDK1 plays a critical role in promoting endothelial cell transition and vascular calcification.
  • CDK1 suppression is a promising therapeutic approach for treating vascular calcification.
  • Targeting CDK1 may offer a novel strategy for managing cardiovascular complications associated with vascular calcification.

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