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Updated: Aug 5, 2025
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
GSK3β Inhibition Reduced Vascular Calcification in Ins2 Mice
Kristina I Boström1,2, Xiaojing Qiao1, Yan Zhao1
1Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USA.
Abstract:
Endothelial-mesenchymal transition (EndMT) drives the endothelium to contribute to vascular calcification in diabetes mellitus. In our previous study, we showed that glycogen synthase kinase-3β (GSK3β) inhibition induces β-catenin and reduces mothers against DPP homolog 1 (SMAD1) to direct osteoblast-like cells toward endothelial lineage, thereby reducing vascular calcification in Matrix Gla Protein (Mgp) deficiency. Here, we report that GSK3β inhibition reduces vascular calcification in diabetic Ins2 mice. Cell lineage tracing reveals that GSK3β inhibition redirects endothelial cell (EC)-derived osteoblast-like cells back to endothelial lineage in the diabetic endothelium of Ins2 mice. We also find that the alterations in β-catenin and SMAD1 by GSK3β inhibition in the aortic endothelium of diabetic Ins2 mice are similar to Mgp mice. Together, our results suggest that GSK3β inhibition reduces vascular calcification in diabetic arteries through a similar mechanism to that in Mgp mice.
Insights
Glycogen synthase kinase-3β (GSK3β) inhibition reduces vascular calcification in diabetic arteries by redirecting endothelial cells. This approach mirrors mechanisms observed in Matrix Gla Protein deficient mice.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Cell Biology
Background:
- Endothelial-mesenchymal transition (EndMT) contributes to vascular calcification in diabetes mellitus.
- Glycogen synthase kinase-3β (GSK3β) inhibition previously showed potential in reducing vascular calcification by modulating cell lineage in Matrix Gla Protein (Mgp) deficiency.
Purpose of the Study:
- To investigate the effect of GSK3β inhibition on vascular calcification in diabetic mice.
- To elucidate the underlying cellular mechanisms, specifically endothelial cell lineage redirection.
Main Methods:
- Utilized diabetic Ins2 mouse model.
- Administered GSK3β inhibition.
- Employed cell lineage tracing techniques.
- Analyzed β-catenin and SMAD1 signaling pathways in aortic endothelium.
Main Results:
- GSK3β inhibition significantly reduced vascular calcification in diabetic Ins2 mice.
- Cell lineage tracing confirmed redirection of endothelial cell-derived osteoblast-like cells back to endothelial lineage.
- Observed similar alterations in β-catenin and SMAD1 signaling as in Mgp-deficient mice.
Conclusions:
- GSK3β inhibition effectively reduces vascular calcification in diabetic arteries.
- The mechanism involves redirecting endothelial cells away from an osteoblast-like phenotype.
- This therapeutic strategy shows promise and shares similarities with previously studied models.
