Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USA.
The Molecular Biology Institute at UCLA, Los Angeles, CA 90095-1570, USA.
Int J Mol Sci. 2023 Jul 19;24(14):11638. doi: 10.3390/ijms241411638.
Endothelial-mesenchymal transition (EndMT) drives endothelium to contribute to atherosclerotic calcification. In a previous study, we showed that glycogen synthase kinase-3β (GSK3β) inhibition induced β-catenin and reduced mothers against DPP homolog 1 (SMAD1) in order to redirect osteoblast-like cells towards endothelial lineage, thereby reducing vascular calcification in deficiency and diabetic mice. Here, we report that GSK3β inhibition or endothelial-specific deletion of GSK3β reduces atherosclerotic calcification. We also find that alterations in β-catenin and SMAD1 induced by GSK3β inhibition in the aortas of mice are similar to mice. Together, our results suggest that GSK3β inhibition reduces vascular calcification in atherosclerotic lesions through a similar mechanism to that in mice.
内皮-间充质转化（EndMT）促使内皮细胞参与动脉粥样硬化钙化。在之前的研究中，我们发现糖原合酶激酶 3β（GSK3β）抑制诱导β-连环蛋白并减少母系抗 DPP 同源物 1（SMAD1），以使成骨样细胞向内皮谱系重定向，从而减少 缺乏症和糖尿病 小鼠的血管钙化。在这里，我们报告 GSK3β 抑制或内皮特异性 GSK3β 缺失可减少动脉粥样硬化钙化。我们还发现，GSK3β 抑制在 小鼠主动脉中诱导的β-连环蛋白和 SMAD1 的改变与 小鼠相似。总之，我们的研究结果表明，GSK3β 抑制通过与 小鼠相似的机制减少动脉粥样硬化病变中的血管钙化。
