Interleukin‐29 Accelerates Vascular Calcification via JAK2/STAT3/BMP2 Signaling

Abstract

Background Vascular calcification (VC), associated with enhanced cardiovascular morbidity and mortality, is characterized by the osteogenic transdifferentiation of vascular smooth muscle cells. Inflammation promotes VC initiation and progression. Interleukin (IL)‐29, a newly discovered member of type III interferon, has recently been implicated in the pathogenesis of autoimmune diseases. Here we evaluated the role of IL‐29 in the VC process and underlying inflammatory mechanisms. Methods and Results The mRNA expression of IL‐29 was significantly increased and positively associated with an increase in BMP2 (bone morphogenetic protein 2) mRNA level in calcified carotid arteries from patients with coronary artery disease or chronic kidney disease. IL‐29 and BMP2 proteins are colocalized in human calcified arteries. IL‐29 binding to its specific receptor IL‐28Rα (IL‐28 receptor α) (IL‐29/IL‐28Rα) inhibited the proliferation of rat vascular smooth muscle cells without altering cell apoptosis or migration. IL‐29 promoted the calcification of rat vascular smooth muscle cells and their osteogenic transdifferentiation in vitro as well as the rat aortic ring calcification ex vivo, induced by the calcification medium or osteogenic medium. The procalcification effect of IL‐29 was reduced by pharmacological inhibition of IL‐29/IL‐28Rα binding as well as suppression of janus kinase 2/signal transducer and activator of transcription pathway activation, accompanied by decreased BMP2 expression in the cultured rat vascular smooth muscle cells. Conclusions These results suggest an important role of IL‐29 in VC development, at least partly, via activating the janus kinase 2/signal transducer and activator of transcription 3 signaling. Inhibition of IL‐29 or its specific receptor, IL‐28Rα, may provide a novel strategy to reduce VC in patients with vascular diseases.

Keywords

• interleukin‐29
• JAK/STAT pathway
• vascular calcification
• vascular smooth muscle cell