{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Toyohara T"],"funding":["NIDDK NIH HHS","National Institute of Diabetes and Digestive and Kidney Diseases","Harvard Stem Cell Institute","National Heart, Lung, and Blood Institute","NHLBI NIH HHS","National Institutes of Health"],"pagination":["147-157.e7"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8530449"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(1)"],"pubmed_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."],"journal":["Cell stem cell"],"pubmed_title":["Patient hiPSCs Identify Vascular Smooth Muscle Arylacetamide Deacetylase as Protective against Atherosclerosis."],"pmcid":["PMC8530449"],"funding_grant_id":["U01HL100408","R01 DK097768","R01HL126901","U01 HL100408","R01 HL126901","R01DK097768"],"pubmed_authors":["Katsuki S","Roudnicky F","Toyohara T","Florido MHC","Nakano T","Lee M","Meissner T","Friesen M","Aikawa M","Davidow LS","Yu H","Rubin LL","Abe T","Cowan CA","Pereira AC","Ptaszek L"],"additional_accession":[]},"is_claimable":false,"name":"Patient hiPSCs Identify Vascular Smooth Muscle Arylacetamide Deacetylase as Protective against Atherosclerosis.","description":"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.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jul","modification":"2026-05-09T09:33:57.333Z","creation":"2025-02-18T23:35:38.515Z"},"accession":"S-EPMC8530449","cross_references":{"pubmed":["32413331"],"doi":["10.1016/j.stem.2020.04.018"]}}