Mechanism of endothelial microparticle-encapsulated miR-204-3p induced vasculitic injury in Kawasaki disease

AIM To investigate the mechanism of miR-204-3p encapsulated in endothelial microparticles (EMP) mediated vascular inflammatory injury in Kawasaki disease (KD).

METHODS From April 2016 to March 2021, 58 KD patients and 50 control subjects were selected for this study. By echocardiographic score, 18 KD patients were with coronary artery aneurysms (CAA) and 40 KD patients were without coronary artery aneurysm (NCAA). EMP was isolated from serum samples of each group and the whole genome miRNA was sequenced. In vitro experiments, VSMC or VSMC pre-transfected with miR-204-3p mimetic (AgomiR-204-3p) and miR-204-3p inhibitor (AntagomiR-204-3p) were co-cultured with EMP in each group.

RESULTS Whole-genome miRNA sequencing and RT-qPCR analysis confirmed that miR-204-3p was significantly increased in KD EMP and the copy number of miR-204-3p in EMP was significantly reduced dependent on the coronary pathology severity, following the order NCAA>SCAA>MCAA>GCAA. VSMC proliferation was significantly reduced (P<0.05), the expression of VSMC differentiation markers (ACTA2 and CNN1) was significantly increased (P<0.05) and the expression of dedifferentiation markers (OPN and PDGFRβ) was significantly reduced (P<0.05) after 48 hours of incubation with NCAA EMP compared with those of control EMP. Dual luciferase reporter gene detection confirmed that miR-204-3p in EMP functionally targeted PDGFRβ in VSMC. In VSMCs incubated with NCAA EMP, the administration of AntagomiR-204-3p significantly reduced the expression of differentiation markers (ACTA2 and CNN1) and increased the expression of dedifferentiation markers (OPN and PDGFRβ). In VSMC incubated with CAA EMP, the administration of AgomiR-204-3p significantly increased the expression of differentiation markers and reduced the expression of dedifferentiation markers.

CONCLUSION EMP transfers miR-204-3p to VSMC and partially mediates KD vasculitis damage by targeting PDGFRβ. Therefore, targeting the miR-204-3p-PDGFRβ axis may provide a novel therapeutic option for KD-induced vascular pathologies.