{"publisher":"eLife Sciences Publications","article_type":"original","article_number":"e54383","file":[{"access_level":"open_access","success":1,"file_id":"11132","relation":"main_file","file_name":"2020_eLife_Bersini.pdf","content_type":"application/pdf","date_created":"2022-04-08T06:53:10Z","file_size":4399825,"date_updated":"2022-04-08T06:53:10Z","checksum":"f8b3821349a194050be02570d8fe7d4b","creator":"dernst"}],"type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa_version":"Published Version","date_published":"2020-09-08T00:00:00Z","pmid":1,"abstract":[{"text":"Vascular dysfunctions are a common feature of multiple age-related diseases. However, modeling healthy and pathological aging of the human vasculature represents an unresolved experimental challenge. Here, we generated induced vascular endothelial cells (iVECs) and smooth muscle cells (iSMCs) by direct reprogramming of healthy human fibroblasts from donors of different ages and Hutchinson-Gilford Progeria Syndrome (HGPS) patients. iVECs induced from old donors revealed upregulation of GSTM1 and PALD1, genes linked to oxidative stress, inflammation and endothelial junction stability, as vascular aging markers. A functional assay performed on PALD1 KD VECs demonstrated a recovery in vascular permeability. We found that iSMCs from HGPS donors overexpressed bone morphogenetic protein (BMP)−4, which plays a key role in both vascular calcification and endothelial barrier damage observed in HGPS. Strikingly, BMP4 concentrations are higher in serum from HGPS vs. age-matched mice. Furthermore, targeting BMP4 with blocking antibody recovered the functionality of the vascular barrier in vitro, hence representing a potential future therapeutic strategy to limit cardiovascular dysfunction in HGPS. These results show that iVECs and iSMCs retain disease-related signatures, allowing modeling of vascular aging and HGPS in vitro.","lang":"eng"}],"oa":1,"title":"Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome","article_processing_charge":"No","language":[{"iso":"eng"}],"date_created":"2022-04-07T07:43:48Z","publication_identifier":{"issn":["2050-084X"]},"file_date_updated":"2022-04-08T06:53:10Z","intvolume":"         9","day":"08","citation":{"ama":"Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/elife.54383\">10.7554/elife.54383</a>","chicago":"Bersini, Simone, Roberta Schulte, Ling Huang, Hannah Tsai, and Martin Hetzer. “Direct Reprogramming of Human Smooth Muscle and Vascular Endothelial Cells Reveals Defects Associated with Aging and Hutchinson-Gilford Progeria Syndrome.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/elife.54383\">https://doi.org/10.7554/elife.54383</a>.","apa":"Bersini, S., Schulte, R., Huang, L., Tsai, H., &#38; Hetzer, M. (2020). Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.54383\">https://doi.org/10.7554/elife.54383</a>","ieee":"S. Bersini, R. Schulte, L. Huang, H. Tsai, and M. Hetzer, “Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","short":"S. Bersini, R. Schulte, L. Huang, H. Tsai, M. Hetzer, ELife 9 (2020).","ista":"Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. 2020. Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. eLife. 9, e54383.","mla":"Bersini, Simone, et al. “Direct Reprogramming of Human Smooth Muscle and Vascular Endothelial Cells Reveals Defects Associated with Aging and Hutchinson-Gilford Progeria Syndrome.” <i>ELife</i>, vol. 9, e54383, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/elife.54383\">10.7554/elife.54383</a>."},"publication":"eLife","month":"09","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"scopus_import":"1","volume":9,"ddc":["570"],"extern":"1","publication_status":"published","status":"public","user_id":"72615eeb-f1f3-11ec-aa25-d4573ddc34fd","date_updated":"2022-07-18T08:30:37Z","has_accepted_license":"1","author":[{"first_name":"Simone","last_name":"Bersini","full_name":"Bersini, Simone"},{"full_name":"Schulte, Roberta","first_name":"Roberta","last_name":"Schulte"},{"full_name":"Huang, Ling","last_name":"Huang","first_name":"Ling"},{"full_name":"Tsai, Hannah","last_name":"Tsai","first_name":"Hannah"},{"orcid":"0000-0002-2111-992X","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"HETZER","first_name":"Martin W","full_name":"HETZER, Martin W"}],"external_id":{"pmid":["32896271"]},"quality_controlled":"1","doi":"10.7554/elife.54383","_id":"11055","year":"2020"}