Suppression of miR-34a Expression in the Myocardium Protects Against Ischemia-Reperfusion Injury Through SIRT1 Protective Pathway

被引：41

作者：

Fu, Bi-Cheng ^{[1
,2
]}

Lang, Ji-Lu ^{[1
,2
]}

Zhang, Dong-Yang ^{[1
,2
]}

Sun, Lu ^{[1
,2
]}

Chen, Wei ^{[1
,2
]}

Liu, Wei ^{[2
]}

Liu, Kai-Yu ^{[1
,2
]}

Ma, Chong-Yi ^{[1
,2
]}

Jiang, Shu-Lin ^{[1
,2
]}

Li, Ren-Ke ^{[3
,4
]}

Tian, Hai ^{[1
,2
]}

机构：

[1] Harbin Med Univ, Dept Cardiovasc Surg, Affiliated Hosp 2, Harbin 150086, Heilongjiang, Peoples R China

[2] Chinese Minist Educ, Key Labs Myocardial Ischemia, Harbin, Heilongjiang, Peoples R China

[3] Univ Hlth Network, Toronto Gen Res Inst, Div Cardiovasc Surg, Toronto, ON, Canada

[4] Univ Toronto, Div Cardiac Surg, Dept Surg, Toronto, ON, Canada

来源：

STEM CELLS AND DEVELOPMENT | 2017年 / 26卷 / 17期

基金：

黑龙江省自然科学基金; 中国国家自然科学基金;

关键词：

apoptosis; cardiomyocytes; ischemia-reperfusion injury; microRNA-34a; SIRT1; STEM-CELLS; IN-VITRO; CARDIAC FIBROSIS; HEART; ISCHEMIA/REPERFUSION; REGULATOR; APOPTOSIS; DIFFERENTIATION; INHIBITION; INFARCTION;

D O I：

10.1089/scd.2017.0062

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

MicroRNA-34a (miR-34a) is expressed in the myocardium and expression is altered after myocardial injury. We investigated the effects of miR-34a on heart function after ischemia-reperfusion (IR) injury. Cardiomyocytes were isolated from neonatal rat hearts and simulated IR injury was induced in vitro. Following IR injury in rats, infarct size was measured and left ventricular (LV) function was evaluated using echocardiography. Protein expression of silent information regulator 1 (SIRT1), acetylated p53 (ac-p53), Bcl-2 and Bax, and miR-34a and SIRT1 gene levels were analyzed. miR-34a overexpression exacerbated myocardial injury by increasing apoptosis and infarct size and decreasing LV function. Suppression of miR-34a attenuated myocardial IR injury. SIRT1 was negatively regulated by miR-34a and the expression of downstream genes, such as ac-p53, Bcl-2, and Bax were altered correspondingly. Increased expression of miR-34a aggravates injury after IR; miR-34a suppression therapy may represent a new line of treatment for myocardial IR injury.

引用

页码：1270 / 1282

页数：13

共 34 条

[1] SIRT1 modulates MAPK pathways in ischemic-reperfused cardiomyocytes [J].

Becatti, Matteo ;

Taddei, Niccolo ;

Cecchi, Cristina ;

Nassi, Niccolo ;

Nassi, Paolo Antonio ;

Fiorillo, Claudia .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2012, 69 (13) :2245-2260

[2] Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart function [J].

Bernardo, Bianca C. ;

Gao, Xiao-Ming ;

Winbanks, Catherine E. ;

Boey, Esther J. H. ;

Tham, Yow Keat ;

Kiriazis, Helen ;

Gregorevic, Paul ;

Obad, Susanna ;

Kauppinen, Sakari ;

Du, Xiao-Jun ;

Lin, Ruby C. Y. ;

McMullen, Julie R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (43) :17615-17620

[3] A MicroRNA Guide for Clinicians and Basic Scientists: Background and Experimental Techniques [J].

Bernardo, Bianca C. ;

Charchar, Fadi J. ;

Lin, Ruby C. Y. ;

McMullen, Julie R. .

HEART LUNG AND CIRCULATION, 2012, 21 (03) :131-142

[4] MicroRNA-34a regulates cardiac ageing and function [J].

Boon, Reinier A. ;

Iekushi, Kazuma ;

Lechner, Stefanie ;

Seeger, Timon ;

Fischer, Ariane ;

Heydt, Susanne ;

Kaluza, David ;

Treguer, Karine ;

Carmona, Guillaume ;

Bonauer, Angelika ;

Horrevoets, Anton J. G. ;

Didier, Nathalie ;

Girmatsion, Zenawit ;

Biliczki, Peter ;

Ehrlich, Joachim R. ;

Katus, Hugo A. ;

Mueller, Oliver J. ;

Potente, Michael ;

Zeiher, Andreas M. ;

Hermeking, Heiko ;

Dimmeler, Stefanie .

NATURE, 2013, 495 (7439) :107-110

[5] Mesenchymal stem cells overexpressing MiR-126 enhance ischemic angiogenesis via the AKT/ERK-related pathway [J].

Chen, Jian-Jun ;

Zhou, Sheng-Hua .

CARDIOLOGY JOURNAL, 2011, 18 (06) :675-681

[6] Berberine reduces ischemia/reperfusion-induced myocardial apoptosis via activating AMPK and PI3K-Akt signaling in diabetic rats [J].

Chen, Keke ;

Li, Guohua ;

Geng, Fenghao ;

Zhang, Zhao ;

Li, Jiani ;

Yang, Min ;

Dong, Ling ;

Gao, Feng .

APOPTOSIS, 2014, 19 (06) :946-957

[7] Combinatorial polymer matrices enhance in vitro maturation of human induced pluripotent stem cell-derived cardiomyocytes [J].

Chun, Young Wook ;

Balikov, Daniel A. ;

Feaster, Tromondae K. ;

Williams, Charles H. ;

Sheng, Calvin C. ;

Lee, Jung-Bok ;

Boire, Timothy C. ;

Neely, M. Diana ;

Bellan, Leon M. ;

Ess, Kevin C. ;

Bowman, Aaron B. ;

Sung, Hak-Joon ;

Hong, Charles C. .

BIOMATERIALS, 2015, 67 :52-64

[8] Myocardial protection in man - from research concept to clinical practice [J].

Cokkinos, Dennis V. ;

Pantos, Costas .

HEART FAILURE REVIEWS, 2007, 12 (3-4) :345-362

[9]

Fan YC, 2014, MOL VIS, V20, P1557

[10] Stepwise Chemically Induced Cardiomyocyte Specification of Human Embryonic Stem Cells [J].

Gonzalez, Rodolfo ;

Lee, Jae Wook ;

Schultz, Peter G. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2011, 50 (47) :11181-11185

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