Inhibition of microRNA-17-5p reduces the inflammation and lipid accumulation, and up-regulates ATP-binding cassette transporterA1 in atherosclerosis
Atherosclerosis (AS) is a chronic inflammatory disease of the arterial wall. Macrophages are considered to be closely associated with the development and progression of AS. However, the precise mechanism of miR-17-5p in the macrophages under AS remains incompletely clarified. This study investigated...
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doaj-59cc5826276b4a2ba6219dfa1a9cec912020-11-25T00:34:52ZengElsevierJournal of Pharmacological Sciences1347-86132019-04-011394280288Inhibition of microRNA-17-5p reduces the inflammation and lipid accumulation, and up-regulates ATP-binding cassette transporterA1 in atherosclerosisLili Tan0Limin Liu1Zhenyu Jiang2Xiaojiao Hao3Department of Cardiology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang 110035, People's Republic of ChinaCorresponding author. Department of Cardiology, The Second Affiliated Hospital of Shenyang Medical College, 64 West Qishan Road, Shenyang 110035, People's Republic of China.; Department of Cardiology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang 110035, People's Republic of ChinaDepartment of Cardiology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang 110035, People's Republic of ChinaDepartment of Cardiology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang 110035, People's Republic of ChinaAtherosclerosis (AS) is a chronic inflammatory disease of the arterial wall. Macrophages are considered to be closely associated with the development and progression of AS. However, the precise mechanism of miR-17-5p in the macrophages under AS remains incompletely clarified. This study investigated the regulatory effect of miR-17-5p on the inflammation and lipid accumulation in mouse macrophages both in vivo and in vitro. It was found that miR-17-5p was highly expressed with lowered ATP-binding cassette transporterA1 (ABCA1) level in the peripheral blood leucocytes (PBLs) of AS patients. Moreover, the level of miR-17-5p was up-regulated in the macrophages of ApoE−/− mice fed with a high-cholesterol diet. Furthermore, we injected miR-17-5p antagomir into AS mice or transfected miR-17-5p inhibitors into mouse macrophage RAW264.7 cells. Results showed that downregulation of miR-17-5p significantly reduced the production of inflammatory cytokines, inhibited the lipid accumulation and up-regulated ABCA1, and activated peroxisome proliferator-activated receptor (PPAR) γ/Liver X receptor (LXR) α signaling pathway. Additionally, ABCA1 was found to be a target of miR-17-5p by directly binding to 3′-untranslated region (3′-UTR) of its mRNA. Our study indicates a novel regulatory mechanism for miR-17-5p by interacting with ABCA1, which could be a therapy-target for the treatment of AS. Keywords: Atherosclerosis, microRNA-17-5p, ATP-Binding cassette transporterA1, Macrophagehttp://www.sciencedirect.com/science/article/pii/S1347861318302172 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lili Tan Limin Liu Zhenyu Jiang Xiaojiao Hao |
spellingShingle |
Lili Tan Limin Liu Zhenyu Jiang Xiaojiao Hao Inhibition of microRNA-17-5p reduces the inflammation and lipid accumulation, and up-regulates ATP-binding cassette transporterA1 in atherosclerosis Journal of Pharmacological Sciences |
author_facet |
Lili Tan Limin Liu Zhenyu Jiang Xiaojiao Hao |
author_sort |
Lili Tan |
title |
Inhibition of microRNA-17-5p reduces the inflammation and lipid accumulation, and up-regulates ATP-binding cassette transporterA1 in atherosclerosis |
title_short |
Inhibition of microRNA-17-5p reduces the inflammation and lipid accumulation, and up-regulates ATP-binding cassette transporterA1 in atherosclerosis |
title_full |
Inhibition of microRNA-17-5p reduces the inflammation and lipid accumulation, and up-regulates ATP-binding cassette transporterA1 in atherosclerosis |
title_fullStr |
Inhibition of microRNA-17-5p reduces the inflammation and lipid accumulation, and up-regulates ATP-binding cassette transporterA1 in atherosclerosis |
title_full_unstemmed |
Inhibition of microRNA-17-5p reduces the inflammation and lipid accumulation, and up-regulates ATP-binding cassette transporterA1 in atherosclerosis |
title_sort |
inhibition of microrna-17-5p reduces the inflammation and lipid accumulation, and up-regulates atp-binding cassette transportera1 in atherosclerosis |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2019-04-01 |
description |
Atherosclerosis (AS) is a chronic inflammatory disease of the arterial wall. Macrophages are considered to be closely associated with the development and progression of AS. However, the precise mechanism of miR-17-5p in the macrophages under AS remains incompletely clarified. This study investigated the regulatory effect of miR-17-5p on the inflammation and lipid accumulation in mouse macrophages both in vivo and in vitro. It was found that miR-17-5p was highly expressed with lowered ATP-binding cassette transporterA1 (ABCA1) level in the peripheral blood leucocytes (PBLs) of AS patients. Moreover, the level of miR-17-5p was up-regulated in the macrophages of ApoE−/− mice fed with a high-cholesterol diet. Furthermore, we injected miR-17-5p antagomir into AS mice or transfected miR-17-5p inhibitors into mouse macrophage RAW264.7 cells. Results showed that downregulation of miR-17-5p significantly reduced the production of inflammatory cytokines, inhibited the lipid accumulation and up-regulated ABCA1, and activated peroxisome proliferator-activated receptor (PPAR) γ/Liver X receptor (LXR) α signaling pathway. Additionally, ABCA1 was found to be a target of miR-17-5p by directly binding to 3′-untranslated region (3′-UTR) of its mRNA. Our study indicates a novel regulatory mechanism for miR-17-5p by interacting with ABCA1, which could be a therapy-target for the treatment of AS. Keywords: Atherosclerosis, microRNA-17-5p, ATP-Binding cassette transporterA1, Macrophage |
url |
http://www.sciencedirect.com/science/article/pii/S1347861318302172 |
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