Silencing of STE20-type kinase STK25 in human aortic endothelial and smooth muscle cells is atheroprotective.
Emmelie CansbySima KumariMara CaputoYing XiaRando PoroskJonathan RobinsonHao WangBritt-Marie OlssonJosefine VallinJulie GranthamUrsel SoometsL Thomas SvenssonCarina SihlbomHanns-Ulrich MarschallAndreas EdsfeldtIsabel GoncalvesMargit MahlapuuPublished in: Communications biology (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.
Keyphrases
- endothelial cells
- endoplasmic reticulum stress
- induced apoptosis
- aortic valve
- single cell
- cell therapy
- left ventricular
- pulmonary artery
- induced pluripotent stem cells
- oxidative stress
- pluripotent stem cells
- aortic dissection
- protein kinase
- skeletal muscle
- systemic sclerosis
- pulmonary arterial hypertension
- pulmonary hypertension
- fatty acid
- cell proliferation