当前位置： SCI文献检索 > CIRCULATION RESEARCH期刊下所有文献 > miR33 inhibition overcomes deleterious effects of diabetes mellitus on atherosclerosis plaque regression in mice.

miR33 inhibition overcomes deleterious effects of diabetes mellitus on atherosclerosis plaque regression in mice.

Abstract：

RATIONALE:Diabetes mellitus increases cardiovascular disease risk in humans and remains elevated despite cholesterol-lowering therapy with statins. Consistent with this, in mouse models, diabetes mellitus impairs atherosclerosis plaque regression after aggressive cholesterol lowering. MicroRNA 33 (miR33) is a key negative regulator of the reverse cholesterol transport factors, ATP-binding cassette transporter A1 and high-density lipoprotein, which suggested that its inhibition may overcome this impairment. OBJECTIVE:To assess the effects of miR33 inhibition on atherosclerosis regression in diabetic mice. METHODS AND RESULTS:Reversa mice, which are deficient in the low-density lipoprotein receptor and in which hypercholesterolemia is reversed by conditional inactivation of the microsomal triglyceride transfer protein gene, were placed on an atherogenic diet for 16 weeks, then either made diabetic by streptozotocin injection or kept normoglycemic. Lipid-lowering was induced by microsomal triglyceride transfer protein gene inactivation, and mice were treated with anti-miR33 or control oligonucleotides. Although regression was impaired in diabetic mice treated with control oligonucleotides, anti-miR33 treatment decreased plaque macrophage content and inflammatory gene expression in these mice. The decreased macrophage content in anti-miR33 treated diabetic mice was associated with a blunting of hyperglycemia-induced monocytosis and reduced monocyte recruitment to the plaque, which was traced to an inhibition of the proliferation of bone marrow monocyte precursors associated with the upregulation of their Abca1. CONCLUSIONS:miR33 inhibition overcomes deleterious effects of diabetes mellitus in atherosclerosis regression in mice, which suggests a therapeutic strategy in diabetic patients, who remain at elevated cardiovascular disease risk, despite plasma cholesterol lowering.

journal_name

Circ Res

journal_title

Circulation research

authors

Distel E,Barrett TJ,Chung K,Girgis NM,Parathath S,Essau CC,Murphy AJ,Moore KJ,Fisher EA

doi

10.1161/CIRCRESAHA.115.304164

subject

Has Abstract

pub_date

2014-10-10 00:00:00

pages

759-69

issue

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.115.304164

journal_volume

115

pub_type

杂志文章

在线工具

miR33 inhibition overcomes deleterious effects of diabetes mellitus on atherosclerosis plaque regression in mice.