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

Autor: Emmelie Cansby, Sima Kumari, Mara Caputo, Ying Xia, Rando Porosk, Jonathan Robinson, Hao Wang, Britt-Marie Olsson, Josefine Vallin, Julie Grantham, Ursel Soomets, L. Thomas Svensson, Carina Sihlbom, Hanns-Ulrich Marschall, Andreas Edsfeldt, Isabel Goncalves, Margit Mahlapuu
Rok vydání: 2021
Předmět:
Zdroj: Communications biology. 5(1)
ISSN: 2399-3642
Popis: 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.
Databáze: OpenAIRE