Endothelial microparticles-mediated transfer of microRNA-19b promotes atherosclerosis via activating perivascular adipose tissue inflammation in apoE-/- mice
Endothelial microparticles-mediated transfer of microRNA-19b promotes atherosclerosis via activating perivascular adipose tissue inflammation in apoE-/- mice
复制标题
内皮微粒介导的 microRNA-19b 转移通过激活 apoE(-/-) 小鼠血管周围脂肪组织炎症促进动脉粥样硬化
DOI:
10.1016/j.bbrc.2017.11.195
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发表时间:
2018-01-08
影响因子:
3.1
通讯作者:
Chen, Hong
中科院分区:
文献类型:
--
作者:
Li, Changlong;Li, Sufang;Chen, Hong
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 EMPm1R19b significantly accelerated carotid artery atherosclerosis progression by increasing lipid, macrophages and smooth muscle cells and decreasing collagen content in atherosclerotic plaque. Fluorescence-labelled EMPm1R19b injection proved that miR-19b could be transported into perivascular adipose tissue(PVAT) by EMPs. EMPm1R19b 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(m1R19b)PVAT(+) and EMP(m1R19b)PVAT(-), based on removing or keeping pericarotid adipose tissue and injected with EMPcontrol or EMP(m1R19b)Loss of PVAT attenuated EMPm1R19b-mediated effects on increasing carotid atherosclerosis formation and inflammatory cytokines level in plaque. EMPm1R19b 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. (C) 2017 Elsevier Inc. All rights reserved.