Endothelial microparticles-mediated transfer of microRNA-19b promotes atherosclerosis via activating perivascular adipose tissue inflammation in apoE−/− mice

Highlights: • EMP^miR19b promotes atherosclerosis progression. • EMP^miR19b increases inflammation in perivascular adipose tissue. • EMP can transfer microRNA-19b into perivascular adipose tissue. • SOCS3 is a direct target of microRNA-19b. Microparticles(MPs) are the major carriers of circulating microRNAs. Our previous study has shown that microRNA (miR)-19b in endothelial cell-derived microparticles (EMPs) is significantly increased in patients with unstable angina. However, little is known about the relationship between miR-19b in EMPs and the progression of atherosclerosis. The aim of the present study was to define the role and potential mechanism of miR-19b incorporated in EMPs in the development of atherosclerosis. Western-diet-fed apoE^−/− mice were injected with phosphate buffered solution(PBS), EMP carrying microRNA control(EMP^control) or miR-19b mimic (EMP^miR19b) intravenously. Systemic treatment with EMP^miR19b significantly accelerated carotid artery atherosclerosis progression by increasing lipid, macrophages and smooth muscle cells and decreasing collagen content in atherosclerotic plaque. Fluorescence-labelled EMP^miR19b injection proved that miR-19b could be transported into perivascular adipose tissue(PVAT) by EMPs. EMP^miR19b treatment also promoted inflammatory cytokines secretion and macrophages infiltration in PVAT. In further experiment, apoE^−/− mice were divided into 3 groups: EMP^controlPVAT(+), EMP^miR19bPVAT(+) and EMP^miR19bPVAT(-), based on removing or keeping pericarotid adipose tissue and injected with EMP^control or EMP^miR19b. Loss of PVAT attenuated EMP^miR19b-mediated effects on increasing carotid atherosclerosis formation and inflammatory cytokines level in plaque. EMP^miR19b inhibited suppressor of cytokine signaling 3 (SOCS3) expression in PVAT. Our findings demonstrate that miR-19b in EMPs exaggerates atherosclerosis progression by augmenting PVAT-specific inflammation proceeded by downregulating SOCS3 expression.