---
_id: '11055'
abstract:
- lang: eng
  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.
article_number: e54383
article_processing_charge: No
article_type: original
author:
- first_name: Simone
  full_name: Bersini, Simone
  last_name: Bersini
- first_name: Roberta
  full_name: Schulte, Roberta
  last_name: Schulte
- first_name: Ling
  full_name: Huang, Ling
  last_name: Huang
- first_name: Hannah
  full_name: Tsai, Hannah
  last_name: Tsai
- first_name: Martin W
  full_name: HETZER, Martin W
  id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
  last_name: HETZER
  orcid: 0000-0002-2111-992X
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>
  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>
  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>.
  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.
  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>.
  short: S. Bersini, R. Schulte, L. Huang, H. Tsai, M. Hetzer, ELife 9 (2020).
date_created: 2022-04-07T07:43:48Z
date_published: 2020-09-08T00:00:00Z
date_updated: 2024-10-14T11:17:02Z
day: '08'
ddc:
- '570'
doi: 10.7554/elife.54383
extern: '1'
external_id:
  pmid:
  - '32896271'
file:
- access_level: open_access
  checksum: f8b3821349a194050be02570d8fe7d4b
  content_type: application/pdf
  creator: dernst
  date_created: 2022-04-08T06:53:10Z
  date_updated: 2022-04-08T06:53:10Z
  file_id: '11132'
  file_name: 2020_eLife_Bersini.pdf
  file_size: 4399825
  relation: main_file
  success: 1
file_date_updated: 2022-04-08T06:53:10Z
has_accepted_license: '1'
intvolume: '         9'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
  issn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Direct reprogramming of human smooth muscle and vascular endothelial cells
  reveals defects associated with aging and Hutchinson-Gilford progeria syndrome
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2020'
...