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Updated: Feb 6, 2026
08:43
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
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Single-Cell Multimodal Profiling Highlights Persistent Aortic Smooth Muscle Cell Changes in Diabetic Mice Despite
Vinay Singh Tanwar1, Vajir Malek1, Jingyi Wang2
1Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute (V.S.T., V.M., Y.L., N.K.M., M.A., L.L., M.A.R., Z.B.C., R.N.), Beckman Research Institute of City of Hope, Duarte, CA.
Arteriosclerosis, Thrombosis, and Vascular Biology
|February 5, 2026
Summary
Type 2 diabetes causes vascular smooth muscle cell (SMC) dysfunction that persists despite glucose control. A drug did not reverse these diabetic changes, highlighting the need for new therapies targeting metabolic memory.
Area of Science:
- Cardiovascular Biology
- Metabolic Diseases
- Epigenetics
Background:
- Type 2 diabetes accelerates vascular complications like hypertension and atherosclerosis.
- Vascular smooth muscle cell (SMC) phenotypic switching is a key driver of these complications and is enhanced in diabetes.
- SMC dysfunction can persist despite glycemic control due to prior hyperglycemia (metabolic memory).
Purpose of the Study:
- To investigate the transcriptomic and epigenomic changes in SMCs during phenotypic transition in type 2 diabetes.
- To examine the effect of glucose normalization on these changes using single-cell multiomics.
Main Methods:
- Type 2 diabetes mice (db/db) were treated with dapagliflozin (DAPA) or vehicle; control mice (db/+) received vehicle.
- Aortas were analyzed using single-cell RNA sequencing, single-cell assay for transposase-accessible chromatin with sequencing, and spatial transcriptomics.
- SMC subtypes, gene expression, chromatin accessibility, and transcription factor activity were assessed.
Main Results:
- Dapagliflozin effectively controlled blood glucose and HbA1c in diabetic mice.
- Diabetes induced decreased SMC contractile pathways and increased fibrosis, inflammation, and endothelial dysfunction markers.
- These diabetes-associated changes in gene expression were only partly reversed by DAPA, while chromatin accessibility changes were not reversed.
- SMC phenotypic transition from contractile to fibromyocyte-like states was associated with increased transcription factor activity.
Conclusions:
- Type 2 diabetes induces significant gene expression and chromatin accessibility changes in aortic SMCs, promoting phenotypic switching.
- These molecular alterations are not effectively reversed by dapagliflozin, indicating limitations in current therapies.
- Novel therapeutic strategies are needed to address the persistent SMC dysfunction driven by the metabolic memory of hyperglycemia.
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