Silencing of STE20-type kinase STK25 in human aortic endothelial and smooth muscle cells is atheroprotective
Journal article, 2022
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.
Author
Emmelie Cansby
University of Gothenburg
Sima Kumari
University of Gothenburg
Mara Caputo
University of Gothenburg
Ying Xia
University of Gothenburg
Rando Porosk
University of Tartu
Jonathan Robinson
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Hao Wang
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Britt Marie Olsson
University of Gothenburg
Josefine Vallin
University of Gothenburg
Julie Grantham
University of Gothenburg
Ursel Soomets
University of Tartu
Thomas Svensson
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
C. Sihlbom
University of Gothenburg
H. U. Marschall
Wallenberg Lab.
Andreas Edsfeldt
Lund University
Skåne University Hospital
Isabel Goncalves
Skåne University Hospital
Lund University
Margit Mahlapuu
University of Gothenburg
Communications Biology
23993642 (eISSN)
Vol. 5 1 379Subject Categories
Cell Biology
Cell and Molecular Biology
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
DOI
10.1038/s42003-022-03309-9
PubMed
35440683