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(EMPcontrol) or miR-19b mimic (EMPmiR19b) intravenously. Systemic treatment with EMPmiR19b significantly accelerated carotid artery atherosclerosis progression by increasing lipid, macrophages and smooth muscle cells and decreasing collagen content in atherosclerotic plaque. Fluorescence-labelled EMPmiR19b injection proved that miR-19b could be transported into perivascular adipose tissue(PVAT) by EMPs. EMPmiR19b treatment also promoted inflammatory cytokines secretion and macrophages infiltration in PVAT. In further experiment, apoE−/− mice were divided into 3 groups: EMPcontrolPVAT(+), EMPmiR19bPVAT(+) and EMPmiR19bPVAT(-), based on removing or keeping pericarotid adipose tissue and injected with EMPcontrol or EMPmiR19b. Loss of PVAT attenuated EMPmiR19b-mediated effects on increasing carotid atherosclerosis formation and inflammatory cytokines level in plaque. EMPmiR19b 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.
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More From: Biochemical and Biophysical Research Communications
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