Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
The Molecular Biology Institute at UCLA, Los Angeles, California, USA.
JCI Insight. 2024 Mar 8;9(5):e176065. doi: 10.1172/jci.insight.176065.
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.
血管钙化是心血管疾病的严重并发症。先前的研究表明内皮谱系细胞向成骨样细胞转化并促进血管钙化。在这里，我们发现抑制细胞周期蛋白依赖性激酶（CDK）可阻止内皮谱系细胞向成骨样细胞转化并减少血管钙化。我们发现，在钙化动脉中的内皮细胞（EC）中，CDK1 被强烈诱导，并且显示出 EC 特异性基因缺失 CDK1 可减少钙化。我们发现限制 CDK1 诱导 E-二十六特异性序列变体 2（ETV2），这负责阻止内皮谱系细胞进行成骨分化。我们还发现抑制 CDK1 可减少糖尿病小鼠模型中的血管钙化。总之，这些结果强调了抑制 CDK1 的重要性，并表明抑制 CDK1 可能是治疗血管钙化的一种潜在选择。
