Silencing of STE20-type kinase STK25 in human aortic endothelial and smooth muscle cells is atheroprotective
Artikel i vetenskaplig tidskrift, 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.
Författare
Emmelie Cansby
Göteborgs universitet
Sima Kumari
Göteborgs universitet
Mara Caputo
Göteborgs universitet
Ying Xia
Göteborgs universitet
Rando Porosk
Tartu Ülikool
Jonathan Robinson
Chalmers, Biologi och bioteknik, Systembiologi
Hao Wang
Chalmers, Biologi och bioteknik, Systembiologi
Britt Marie Olsson
Göteborgs universitet
Josefine Vallin
Göteborgs universitet
Julie Grantham
Göteborgs universitet
Ursel Soomets
Tartu Ülikool
Thomas Svensson
Chalmers, Biologi och bioteknik, Systembiologi
C. Sihlbom
Göteborgs universitet
H. U. Marschall
Wallenberg Lab.
Andreas Edsfeldt
Lunds universitet
Skånes universitetssjukhus (SUS)
Isabel Goncalves
Skånes universitetssjukhus (SUS)
Lunds universitet
Margit Mahlapuu
Göteborgs universitet
Communications Biology
23993642 (eISSN)
Vol. 5 1 379Ämneskategorier
Cellbiologi
Cell- och molekylärbiologi
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
DOI
10.1038/s42003-022-03309-9
PubMed
35440683