miRNA 146b-5p protects against atherosclerosis by inhibiting vascular smooth muscle cell proliferation and migration

被引：19

作者：

Sun, Dating ^{[1
]}

Xiang, Gui ^{[2
]}

Wang, Jing ^{[1
]}

Li, Yuanyuan ^{[1
]}

Mei, Shuai ^{[1
]}

Ding, Hu ^{[1
]}

Yan, Jiangtao ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Div Cardiol, Wuhan, Peoples R China

[2] Fujian Med Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Fuzhou, Peoples R China

来源：

EPIGENOMICS | 2020年 / 12卷 / 24期

关键词：

atherosclerosis; epigenetics; inflammation; migration; miR-146b; neointima formation; proliferation; vascular smooth muscle cells; SIGNALING PATHWAY; INFLAMMATION; DISEASE; EXPRESSION; PATHOGENESIS; MIR-146B-5P; INVASION;

D O I：

10.2217/epi-2020-0155

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Aim:To explore the potentially important role of miRNA 146b-5p (miR-146b) during the development of atherosclerosis.Materials & methods:Proliferation, migration and luciferase assays and mouse models were used to determine the functions of miR-146b.Results:miR-146b was identified as substantially upregulated in the aortic plaques ofApoE-/- mice as well as in response to inflammatory cytokines. Overexpression of miR-146b repressed proliferation and migration of vascular smooth muscle cells by downregulatingBag1andMmp16, respectively. Adeno-associated virus-mediated miR-146b overexpression inhibited neointima formation after carotid injury and suppressed atherosclerotic plaque formation in western diet-inducedApoE-/- mice.Conclusion:miR-146b is a novel regulator of vascular smooth muscle cell function induced by inflammatory response, specifically in neointima formation, and offers a novel therapeutic strategy for treating atherosclerosis.

引用

页码：2189 / 2204

页数：16

共 37 条

[1] Knockout of Adamts7, a Novel Coronary Artery Disease Locus in Humans, Reduces Atherosclerosis in Mice [J].

Bauer, Robert C. ;

Tohyama, Junichiro ;

Cui, Jian ;

Cheng, Lan ;

Yang, Jifu ;

Zhang, Xuan ;

Ou, Kristy ;

Paschos, Georgios K. ;

Zheng, X. Long ;

Parmacek, Michael S. ;

Rader, Daniel J. ;

Reilly, Muredach P. .

CIRCULATION, 2015, 131 (13) :1202-+

[2] MicroRNA-221/222 expression in atherosclerotic coronary artery plaque versus internal mammarian artery and in peripheral blood samples [J].

Bildirici, Aslihan Esra ;

Arslan, Serdal ;

Sahin, Nil Ozbilum ;

Berkan, Ocal ;

Beton, Osman ;

Yilmaz, Mehmet Birhan .

BIOMARKERS, 2018, 23 (07) :670-675

[3] Paradoxical Suppression of Atherosclerosis in the Absence of microRNA-146a [J].

Cheng, Henry S. ;

Besla, Rickvinder ;

Li, Angela ;

Chen, Zhiqi ;

Shikatani, Eric A. ;

Nazari-Jahantigh, Maliheh ;

Hammoutene, Adel ;

My-Anh Nguyen ;

Geoffrion, Michele ;

Cai, Lei ;

Khyzha, Nadiya ;

Li, Tong ;

MacParland, Sonya A. ;

Husain, Mansoor ;

Cybulsky, Myron I. ;

Boulanger, Chantal M. ;

Temel, Ryan E. ;

Schober, Andreas ;

Rayner, Katey J. ;

Robbins, Clinton S. ;

Fish, Jason E. .

CIRCULATION RESEARCH, 2017, 121 (04) :354-+

[4] MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways [J].

Cheng, Henry S. ;

Sivachandran, Nirojini ;

Lau, Andrew ;

Boudreau, Emilie ;

Zhao, Jimmy L. ;

Baltimore, David ;

Delgado-Olguin, Paul ;

Cybulsky, Myron I. ;

Fish, Jason E. .

EMBO MOLECULAR MEDICINE, 2013, 5 (07) :1017-1034

[5] MicroRNA-146a and microRNA-146b expression and anti-inflammatory function in human airway smooth muscle [J].

Comer, Brian S. ;

Camoretti-Mercado, Blanca ;

Kogut, Paul C. ;

Halayko, Andrew J. ;

Solway, Julian ;

Gerthoffer, William T. .

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2014, 307 (09) :L727-L734

[6] Metformin and Vascular Diseases: A Focused Review on Smooth Muscle Cell Function [J].

Deng, Mingying ;

Su, Dan ;

Xu, Suowen ;

Little, Peter J. ;

Feng, Xiaojun ;

Tang, Liqin ;

Shen, Aizong .

FRONTIERS IN PHARMACOLOGY, 2020, 11

[7] Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies [J].

Dzau, VJ ;

Braun-Dullaeus, RC ;

Sedding, DG .

NATURE MEDICINE, 2002, 8 (11) :1249-1256

[8] MicroRNA Regulation of Atherosclerosis [J].

Feinberg, Mark W. ;

Moore, Kathryn J. .

CIRCULATION RESEARCH, 2016, 118 (04) :703-720

[9] Noncoding RNAs in Cardiovascular Disease: Pathological Relevance and Emerging Role as Biomarkers and Therapeutics [J].

Gangwar, Roopesh S. ;

Rajagopalan, Sanjay ;

Natarajan, Rama ;

Deiuliis, Jeffrey A. .

AMERICAN JOURNAL OF HYPERTENSION, 2018, 31 (02) :150-165

[10] Smooth muscle cell phenotypic switching in atherosclerosis [J].

Gomez, Delphine ;

Owens, Gary K. .

CARDIOVASCULAR RESEARCH, 2012, 95 (02) :156-164

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