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

摘要

Abstract 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 control PVAT(+), EMP miR19b PVAT(+) and EMP miR19b PVAT(-), 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. 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.