Myocardial infarction-induced hippocampal microtubule damage by cardiac originating microRNA-1 in mice

被引：35

作者：

Sun, Lin-Lin ^{[1
]}

Duan, Ming-Jing ^{[1
]}

Ma, Ji-Chao ^{[1
]}

Xu, Ling ^{[1
]}

Mao, Meng ^{[1
]}

Biddyut, Das ^{[1
]}

Wang, Qin ^{[1
]}

Yang, Chao ^{[1
]}

Zhang, Shuai ^{[1
]}

Xu, Yi ^{[1
]}

Yang, Lin ^{[1
]}

Tian, You ^{[1
]}

Liu, Ying ^{[1
]}

Xia, Sheng-Nan ^{[1
]}

Li, Ke-Xin ^{[1
]}

Jin, Zhuo ^{[1
]}

Xiong, Qiaojie ^{[2
]}

Ai, Jing ^{[1
]}

机构：

[1] Harbin Med Univ, Dept Pharmacol, State Prov Key Labs Biomed Pharmaceut China, Coll Pharm, Harbin 150086, Heilongjiang, Peoples R China

[2] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA

来源：

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY | 2018年 / 120卷

基金：

中国国家自然科学基金;

关键词：

MicroRNA-1; Myocardial infarction; Brain; Neuronal microtubule; TPPP/p25; Exosome; CHRONIC BRAIN HYPOPERFUSION; MUSCLE-SPECIFIC MICRORNA; HEART-FAILURE; ALZHEIMERS-DISEASE; CELLS; EXOSOMES; DISORDERS; TPPP/P25; DEMENTIA; RATS;

D O I：

10.1016/j.yjmcc.2018.05.009

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Cardiovascular diseases are risk factors for dementia, but the mechanisms remain elusive. Here, we report that myocardial infarction (MI) generated by the ligation of the left coronary artery (LCA) could lead to increased miR-1 levels in the hippocampus and blood with neuronal microtubule damage and decreased TPPP/p25 protein expression in the hippocampus. These changes could be prevented by a knockdown of miR-1 using hippocampal stereotaxic injections of anti-miR-1 oligonucleotide fragments carried by a lentivirus vector (lenti-pre-AMO-miR-1). TPPP/p25 protein was downregulated by miR-1 overexpression, upregulated by miR-1 inhibition, and unchanged by binding-site mutations or miR-masks, indicating that the TPPP/p25 gene was a potential target for miR-1. Additionally, the pharmacological inhibition of sphingomyelinase by GW4869 to inhibit exosome generation in the heart significantly attenuated the increased miR-1 levels in the hippocampi of transgenic (Tg) and MI mice. Collectively, the present study demonstrates that MI could directly lead to neuronal microtubule damage independent of MI-induced chronic brain hypoperfusion but involving the overexpression of miR-1 in the hippocampus that was transported by exosomes from infarcted hearts. This study reveals a novel insight into the molecular mechanisms of heart-to-brain communication at the miRNA level.

引用

页码：12 / 27

页数：16

共 52 条

[41] MicroRNA-1 Regulates Cardiomyocyte Apoptosis by Targeting Bd-2 [J].