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Patient hiPSCs Identify Vascular Smooth Muscle Arylacetamide Deacetylase as Protective against Atherosclerosis
- Source :
- Cell Stem Cell
- Publication Year :
- 2019
-
Abstract
- Although susceptibility to cardiovascular disease (CVD) is different for every patient, why some patients with type 2 diabetes mellitus (T2DM) develop CVD while others are protected has not yet been clarified. Using T2DM-patient-derived human induced pluripotent stem cells (hiPSCs), we found that in patients protected from CVD, there was significantly elevated expression of an esterase, arylacetamide deacetylase (AADAC), in vascular smooth muscle cells (VSMCs). We overexpressed this esterase in human primary VSMCs and VSMCs differentiated from hiPSCs and observed that the number of lipid droplets was significantly diminished. Further metabolomic analyses revealed a marked reduction in storage lipids and an increase in membrane phospholipids, suggesting changes in the Kennedy pathway of lipid bioassembly. Cell migration and proliferation were also significantly decreased in AADAC-overexpressing VSMCs. Moreover, apolipoprotein E (Apoe)-knockout mice overexpressing VSMC-specific Aadac showed amelioration of atherosclerotic lesions. Our findings suggest that higher AADAC expression in VSMCs protects T2DM patients from CVD.
- Subjects :
- Apolipoprotein E
medicine.medical_specialty
Vascular smooth muscle
Cell
Induced Pluripotent Stem Cells
Myocytes, Smooth Muscle
Biology
Article
Muscle, Smooth, Vascular
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Lipid droplet
Internal medicine
Genetics
medicine
Animals
Humans
Cells, Cultured
030304 developmental biology
Cell Proliferation
0303 health sciences
Cholesterol
Cell migration
Lipid metabolism
Cell Biology
musculoskeletal system
Atherosclerosis
Endothelial stem cell
Mice, Inbred C57BL
Endocrinology
medicine.anatomical_structure
chemistry
Diabetes Mellitus, Type 2
cardiovascular system
Cancer research
Molecular Medicine
Stem cell
Arylacetamide deacetylase
biology.gene
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 18759777
- Volume :
- 27
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell stem cell
- Accession number :
- edsair.doi.dedup.....7e16e856cd1623dd514f0d64c6f1b285