@article{ae744e9b574441ab941c62906a6f3e9c,
title = "Patient hiPSCs Identify Vascular Smooth Muscle Arylacetamide Deacetylase as Protective against Atherosclerosis",
abstract = "Why some patients with type 2 diabetes are protected against cardiovascular disease (CVD) has not been clarified. Toyohara et al. reveal that in patients protected from CVD, arylacetamide deacetylase (AADAC) is elevated in vascular smooth muscle cells (VSMCs). AADAC alters lipid metabolism and cellular processes in VSMCs and ameliorates CVD.",
keywords = "cardiovascular disease, diabetes, induced pluripotent stem cell, disease modeling, lipid metabolism, cholesterol, Kennedy pathway, arylacetamide deacetylase, vascular smooth muscle cell, endothelial cell",
author = "Takafumi Toyohara and Filip Roudnicky and Florido, {Mary H.C.} and Toshiaki Nakano and Haojie Yu and Shunsuke Katsuki and Minjin Lee and Torsten Meissner and Max Friesen and Davidow, {Lance S.} and Leon Ptaszek and Takaaki Abe and Rubin, {Lee L.} and Pereira, {Alexandre C.} and Masanori Aikawa and Cowan, {Chad A.}",
note = "Funding Information: We would like to first thank all the members of the Cowan laboratory. We also thank Lin Wu, Zhenjuan Wang, and Sarah Johnson at Harvard University{\textquoteright}s Genome Modification Facility for generating AADAC-Tg mice and AADAC knockout mice; Justus Ackermann and Jens Bruning for the conditional overexpression cassette; and Jorge Plutzky for the protocol of mouse VSMC isolation. In addition, we thank Ying Shao and Laurence Daheron at Harvard Stem Cell Institute{\textquoteright}s iPS Core for generating iPSCs from T2DM patients and Rocky Stroud for assistance in revising the manuscript. Patricia Sheridan and Lisa White at Metabolon assisted with our metabolomic and lipidomic analyses. Barrett Lee at the imaging core and Lay-Hong Ang at the BIDMC confocal core supported our imaging experiments. Vladimir Ghukasyan (Carl Zeiss) assisted with the cholesterol crystal detection. Miki Yoshizawa and Fumiko Date at Biomedical Research Core of Tohoku University Graduate School of Medicine supported our histological analysis. We also thank the Biomedical Research Unit of Tohoku University Hospital for technical support. Chitose Suzuki, Kiyomi Kisu, and Alastair Poole also assisted in our experiments. These studies were supported by Roche Pharmaceuticals (C.A.C., F. Hoffman-LaRoche / A203889 ), the National Institutes of Health (C.A.C., NIDDK / R01DK097768 and NHLBI / U01HL100408 ; M.A., NHLBI / R01HL126901 ), and the Harvard Stem Cell Institute (C.A.C.). Funding Information: We would like to first thank all the members of the Cowan laboratory. We also thank Lin Wu, Zhenjuan Wang, and Sarah Johnson at Harvard University's Genome Modification Facility for generating AADAC-Tg mice and AADAC knockout mice; Justus Ackermann and Jens Bruning for the conditional overexpression cassette; and Jorge Plutzky for the protocol of mouse VSMC isolation. In addition, we thank Ying Shao and Laurence Daheron at Harvard Stem Cell Institute's iPS Core for generating iPSCs from T2DM patients and Rocky Stroud for assistance in revising the manuscript. Patricia Sheridan and Lisa White at Metabolon assisted with our metabolomic and lipidomic analyses. Barrett Lee at the imaging core and Lay-Hong Ang at the BIDMC confocal core supported our imaging experiments. Vladimir Ghukasyan (Carl Zeiss) assisted with the cholesterol crystal detection. Miki Yoshizawa and Fumiko Date at Biomedical Research Core of Tohoku University Graduate School of Medicine supported our histological analysis. We also thank the Biomedical Research Unit of Tohoku University Hospital for technical support. Chitose Suzuki, Kiyomi Kisu, and Alastair Poole also assisted in our experiments. These studies were supported by Roche Pharmaceuticals (C.A.C. F. Hoffman-LaRoche/A203889), the National Institutes of Health (C.A.C. NIDDK/R01DK097768 and NHLBI/U01HL100408; M.A. NHLBI/R01HL126901), and the Harvard Stem Cell Institute (C.A.C.). Conceptualization, T.T. and C.A.C.; Methodology, T.T. F.R. and C.A.C.; Formal Analysis, T.T. F.R. T.N. M.L. L.D. and C.A.C.; Investigation, T.T. F.R. M.H.C.F. T.N. H.Y. S.K. M.L. T.M. M.F. T.A. A.C.P. and C.A.C.; Resources, L.S.D. L.P. and L.R.; Writing ? Original Draft, T.T. F.R. M.H.C.F. and C.A.C.; Writing ? Review & Editing, T.T. and C.A.C.; Visualization, T.T. and C.A.C.; Supervision, T.T. M.A. and C.A.C.; Project Administration, T.T. and C.A.C.; Funding Acquisition, C.A.C. C.A.C is a founder of CRISPR Therapeutics and Sana Biotechnology. F.R. is an employee of F. Hoffmann-La Roche. Neither a reagent nor any funding from F. Hoffmann-La Roche was used in this study. Publisher Copyright: {\textcopyright} 2020",
year = "2020",
month = jul,
day = "2",
doi = "10.1016/j.stem.2020.04.018",
language = "English",
volume = "27",
pages = "147--157.e7",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "1",
}
