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Silencing of STE20-type kinase STK25 in human aortic endothelial and smooth muscle cells is atheroprotective

Cansby, Emmelie ; Kumari, Sima ; Caputo, Mara ; Xia, Ying ; Porosk, Rando ; Robinson, Jonathan ; Wang, Hao LU ; Olsson, Britt-Marie ; Vallin, Josefine and Grantham, Julie , et al. (2022) In Communications Biology 5. p.1-14
Abstract

Recent studies highlight the importance of lipotoxic damage in aortic cells as the major pathogenetic contributor to atherosclerotic disease. Since the STE20-type kinase STK25 has been shown to exacerbate ectopic lipid storage and associated cell injury in several metabolic organs, we here investigate its role in the main cell types of vasculature. We depleted STK25 by small interfering RNA in human aortic endothelial and smooth muscle cells exposed to oleic acid and oxidized LDL. In both cell types, the silencing of STK25 reduces lipid accumulation and suppresses activation of inflammatory and fibrotic pathways as well as lowering oxidative and endoplasmic reticulum stress. Notably, in smooth muscle cells, STK25 inactivation hinders... (More)

Recent studies highlight the importance of lipotoxic damage in aortic cells as the major pathogenetic contributor to atherosclerotic disease. Since the STE20-type kinase STK25 has been shown to exacerbate ectopic lipid storage and associated cell injury in several metabolic organs, we here investigate its role in the main cell types of vasculature. We depleted STK25 by small interfering RNA in human aortic endothelial and smooth muscle cells exposed to oleic acid and oxidized LDL. In both cell types, the silencing of STK25 reduces lipid accumulation and suppresses activation of inflammatory and fibrotic pathways as well as lowering oxidative and endoplasmic reticulum stress. Notably, in smooth muscle cells, STK25 inactivation hinders the shift from a contractile to a synthetic phenotype. Together, we provide several lines of evidence that antagonizing STK25 signaling in human aortic endothelial and smooth muscle cells is atheroprotective, highlighting this kinase as a new potential therapeutic target for atherosclerotic disease.

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organization
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type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis/genetics, Humans, Intracellular Signaling Peptides and Proteins/metabolism, Lipid Metabolism/genetics, Lipids, Myocytes, Smooth Muscle/metabolism, Protein Serine-Threonine Kinases/genetics
in
Communications Biology
volume
5
article number
379
pages
1 - 14
publisher
Nature Publishing Group
external identifiers
  • pmid:35440683
  • scopus:85128419108
ISSN
2399-3642
DOI
10.1038/s42003-022-03309-9
language
English
LU publication?
yes
additional info
© 2022. The Author(s).
id
e5ba1969-39b0-4c8d-a006-77c9244a2c43
date added to LUP
2022-06-02 11:15:52
date last changed
2024-06-13 17:42:46
@article{e5ba1969-39b0-4c8d-a006-77c9244a2c43,
  abstract     = {{<p>Recent studies highlight the importance of lipotoxic damage in aortic cells as the major pathogenetic contributor to atherosclerotic disease. Since the STE20-type kinase STK25 has been shown to exacerbate ectopic lipid storage and associated cell injury in several metabolic organs, we here investigate its role in the main cell types of vasculature. We depleted STK25 by small interfering RNA in human aortic endothelial and smooth muscle cells exposed to oleic acid and oxidized LDL. In both cell types, the silencing of STK25 reduces lipid accumulation and suppresses activation of inflammatory and fibrotic pathways as well as lowering oxidative and endoplasmic reticulum stress. Notably, in smooth muscle cells, STK25 inactivation hinders the shift from a contractile to a synthetic phenotype. Together, we provide several lines of evidence that antagonizing STK25 signaling in human aortic endothelial and smooth muscle cells is atheroprotective, highlighting this kinase as a new potential therapeutic target for atherosclerotic disease.</p>}},
  author       = {{Cansby, Emmelie and Kumari, Sima and Caputo, Mara and Xia, Ying and Porosk, Rando and Robinson, Jonathan and Wang, Hao and Olsson, Britt-Marie and Vallin, Josefine and Grantham, Julie and Soomets, Ursel and Svensson, L Thomas and Sihlbom, Carina and Marschall, Hanns-Ulrich and Edsfeldt, Andreas and Goncalves, Isabel and Mahlapuu, Margit}},
  issn         = {{2399-3642}},
  keywords     = {{Atherosclerosis/genetics; Humans; Intracellular Signaling Peptides and Proteins/metabolism; Lipid Metabolism/genetics; Lipids; Myocytes, Smooth Muscle/metabolism; Protein Serine-Threonine Kinases/genetics}},
  language     = {{eng}},
  pages        = {{1--14}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Communications Biology}},
  title        = {{Silencing of STE20-type kinase STK25 in human aortic endothelial and smooth muscle cells is atheroprotective}},
  url          = {{http://dx.doi.org/10.1038/s42003-022-03309-9}},
  doi          = {{10.1038/s42003-022-03309-9}},
  volume       = {{5}},
  year         = {{2022}},
}