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MicroRNA cardiac fibrosis

Jiaxin Li, Yingnan Dai, Zhendong Su, Guoqian Wei
To investigate the effects of miR-9 on high glucose (HG)-induced cardiac fibrosis in human cardiac fibroblasts (HCFs), and to establish the mechanism underlying these effects. HCFs were transfected with miR-9 inhibitor or mimic, and then treated with normal or high glucose. Cell viability and proliferation were detected by using the Cell Counting Kit-8 (CCK-8) assay and Brdu-ELISA assay. Cell differentiation and collagen accumulation of HCFs were detected by qRT-PCR and Western blot assays, respectively...
October 18, 2016: Bioscience Reports
Lichan Tao, Yihua Bei, Ping Chen, Zhiyong Lei, Siyi Fu, Haifeng Zhang, Jiahong Xu, Lin Che, Xiongwen Chen, Joost Pg Sluijter, Saumya Das, Dragos Cretoiu, Bin Xu, Jiuchang Zhong, Junjie Xiao, Xinli Li
Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, α-SMA staining, and expression levels of fibrosis-associated genes...
2016: Theranostics
Lingqian Chang, Daniel Gallego-Perez, Chi-Ling Chiang, Paul Bertani, Tairong Kuang, Yan Sheng, Feng Chen, Zhou Chen, Junfeng Shi, Hao Yang, Xiaomeng Huang, Veysi Malkoc, Wu Lu, Ly James Lee
While electroporation has been widely used as a physical method for gene transfection in vitro and in vivo, its application in gene therapy of cardiovascular cells remains challenging. Due to the high concentration of ion-transport proteins in the sarcolemma, conventional electroporation of primary cardiomyocytes tends to cause ion-channel activation and abnormal ion flux, resulting in low transfection efficiency and high mortality. In this work, a high-throughput nanoelectroporation technique based on a nanochannel array platform is reported, which enables massively parallel delivery of genetic cargo (microRNA, plasmids) into mouse primary cardiomyocytes in a controllable, highly efficient, and benign manner...
September 20, 2016: Small
Zi-Dong Bie, Li-Ye Sun, Chuan-Liang Geng, Qing-Guo Meng, Xiao-Jing Lin, Yu-Feng Wang, Xue-Ban Wang, Jun Yang
Myocardial fibrosis (MF), which typically occurs after a myocardial infarction (MI), is a major factor involved in the process of ventricular remodeling and subsequent progression to heart failure. Current studies have found that various microRNAs (miRNAs), such as miR-125b, play an important role in this process. However, few studies have investigated the specific mechanism of miR-125b. Transfection of miR-125b mimics into cardiac fibroblasts (CFs) resulted in significantly increased expression of the myofibroblast marker alpha-smooth muscle actin (α-SMA) and vinculin by Western blot analysis, while transfection of miR-125b inhibitors resulted in the opposite effect...
November 2016: Cell Biology International
Klara Piletič, Tanja Kunej
MicroRNAs (miRNAs) are short non-coding RNAs that act as important regulators of gene expression as part of the epigenetic machinery. In addition to posttranscriptional gene silencing by miRNAs, the epigenetic mechanisms also include DNA methylation, histone modifications and their crosstalk. Epigenetic modifications were reported to play an important role in many disease onsets and progressions and can be used to explain several features of complex diseases, such as late onset and fluctuation of symptoms. However, miRNAs not only function as a part of epigenetic machinery, but are also epigenetically modified by DNA methylation and histone modification like any other protein-coding gene...
October 2016: Archives of Toxicology
Li-Ye Sun, Zi-Dong Bie, Chuan-Huan Zhang, Hua Li, Liu-Dong Li, Jun Yang
Excessive proliferation of cardiac fibroblasts (CFs) and their transdifferentiation into myofibroblasts leads to expression of α-smooth muscle actin (α-SMA), as well as excessive synthesis and secretion of collagens. This process represents an important pathological basis for myocardial fibrosis (MF). MicroRNA (miR)-154 and the Wnt signaling pathway play key roles in the above process, although their specific interactions are poorly understood. After transfecting CFs with miR-154 mimics or inhibitors, miR-154 was found to inhibit the expression of Dickkopf-related protein 2 (DKK2), while miR-154 inhibitors upregulated DKK2 expression in a western blot analysis...
August 20, 2016: Cell Biology International
Qiuyun Wu, Lei Han, Weiwen Yan, Xiaoming Ji, Ruhui Han, Jingjin Yang, Jiali Yuan, Chunhui Ni
Silicosis is an incurable occupational disease associated with inflammation, fibroblast proliferation and the accumulation of extracellular matrix in lung tissues. The dysregulation of lncRNAs and miRNAs has been implicated in many complex diseases; however, the current understanding of their roles in fibrotic lung diseases, especially silicosis, remains limited. Our previous microRNA (miRNA, miR) microarray data have indicated decreased expression levels of miR-489 in lung tissues of silica-induced pulmonary fibrosis...
2016: Scientific Reports
Weijie Du, Haihai Liang, Xu Gao, Xiaoxue Li, Yue Zhang, Zhenwei Pan, Cui Li, Yuying Wang, Yanxin Liu, Wei Yuan, Ning Ma, Wenfeng Chu, Hongli Shan, Yanjie Lu
BACKGROUND/AIMS: Deregulated myocardial fibrosis is associated with a wide spectrum of cardiac conditions, being considered one of the major causes for heart disease. Our study was designed to investigate the role of microRNA-328 (miR-328) in regulating cardiac fibrosis. METHODS: We induced cardiac fibrosis following MI by occlusion of the left coronary artery in C57BL/6 mice. Real-time PCR was employed to evaluate the level of miR-328. Masson's Trichrome stain was used to evaluate the development of fibrosis...
2016: Cellular Physiology and Biochemistry
Xiaoxin Zheng, Xiaoyan Li, Yongnan Lyu, Yiyu He, Weiguo Wan, Xuejun Jiang
BACKGROUND The role of renal sympathetic denervation (RSD) in ameliorating post-myocardial infarction (MI) left ventricular (LV) fibrosis via microRNA-dependent regulation of connective tissue growth factor (CTGF) remains unknown. MATERIAL AND METHODS MI and RSD were induced in Sprague-Dawley rats by ligating the left coronary artery and denervating the bilateral renal nerves, respectively. Norepinephrine, renin, angiotensin II and aldosterone in plasma, collagen, microRNA21, microRNA 101a, microRNA 133a and CTGF in heart tissue, as well as cardiac function were evaluated six weeks post-MI...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Vassilios J Bezzerides, Colin Platt, Carolin Lerchenmüller, Kaavya Paruchuri, Nul Loren Oh, Chunyang Xiao, Yunshan Cao, Nina Mann, Bruce M Spiegelman, Anthony Rosenzweig
The mechanisms by which exercise mediates its multiple cardiac benefits are only partly understood. Prior comprehensive analyses of the cardiac transcriptional components and microRNAs dynamically regulated by exercise suggest that the CBP/p300-interacting protein CITED4 is a downstream effector in both networks. While CITED4 has documented functional consequences in neonatal cardiomyocytes in vitro, nothing is known about its effects in the adult heart. To investigate the impact of cardiac CITED4 expression in adult animals, we generated transgenic mice with regulated, cardiomyocyte-specific CITED4 expression...
June 16, 2016: JCI Insight
Cécile Oury, Laurence Servais, Nassim Bouznad, Alexandre Hego, Alain Nchimi, Patrizio Lancellotti
miRNAs are a class of over 5000 noncoding RNAs that regulate more than half of the protein-encoding genes by provoking their degradation or preventing their translation. miRNAs are key regulators of complex biological processes underlying several cardiovascular disorders, including left ventricular hypertrophy, ischemic heart disease, heart failure, hypertension and arrhythmias. Moreover, circulating miRNAs herald promise as biomarkers in acute myocardial infarction and heart failure. In this context, this review gives an overview of studies that suggest that miRNAs could also play a role in valvular heart diseases...
2016: International Journal of Molecular Sciences
Zhengrong Huang, Xiao-Jun Chen, Cheng Qian, Qian Dong, Dan Ding, Qiong-Feng Wu, Jing Li, Hong-Fei Wang, Wei-Hua Li, Qiang Xie, Xiang Cheng, Ning Zhao, Yi-Mei Du, Yu-Hua Liao
BACKGROUND: Postoperative atrial fibrillation is a frequent complication in cardiac surgery. The aberrant activation of signal transducer and activator of transcription 3 (STAT3) contributes to the pathogenesis of atrial fibrillation. MicroRNA-21 (miR-21) promotes atrial fibrosis. Recent studies support the existence of reciprocal regulation between STAT3 and miR-21. Here, we test the hypothesis that these 2 molecules might form a feedback loop that contributes to postoperative atrial fibrillation by promoting atrial fibrosis...
July 2016: Circulation. Arrhythmia and Electrophysiology
Rui Li, Hai-Hua Geng, Jie Xiao, Xiao-Teng Qin, Fu Wang, Jun-Hui Xing, Yan-Fei Xia, Yang Mao, Jing-Wen Liang, Xiao-Ping Ji
miRs (microRNAs, miRNAs) intricately regulate physiological and pathological processes. Although miR-7a/b protects against cardiomyocyte injury in ischemia/reperfusion injury, the function of miR-7a/b in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Here, we sought to investigate the function of miR-7a/b in post-MI remodeling in a mouse model and to determine the underlying mechanisms involved. miR-7a/b overexpression improved cardiac function, attenuated cardiac remodeling and reduced fibrosis and apoptosis, whereas miR-7a/b silencing caused the opposite effects...
2016: Scientific Reports
Hua Dong, Shimin Dong, Lisi Zhang, Xueping Gao, Guangwei Lv, Wei Chen, Suxia Shao
The miRNAs play important roles in regulating myocardial fibrosis. The purpose of this study was to determine the potential roles of microRNA-214 (miR-214) in cardiac fibrosis in vitro and in vivo. In vitro experiment, Ang II-induced cardiac fibroblasts (CFBs) are transfected with pre-miR-214, anti-miR-214 and their oligo controls. Gene expression was checked by Quantitative realtime-PCR (qRT-PCR) and western blotting. In the present experiment, compared with controls, expressions of collagen type I (COL I), collagen type III (COL III), transforming growth factor (TGF)-β1, and tissue inhibitors of metalloproteinase (TIMP)-1 were all increased, but matrix metalloproteinase (MMP)-1 was reduced in CFB by Ang II treatment at both mRNA and protein levels, and these alterations were found reversed by miR-214 transfection...
October 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Christian Besler, Daniel Urban, Stefan Watzka, David Lang, Karl-Philipp Rommel, Reinhard Kandolf, Karin Klingel, Holger Thiele, Axel Linke, Gerhard Schuler, Volker Adams, Philipp Lurz
AIMS: Inflammatory heart disease represents an important cause of chronic dilated cardiomyopathy (DCM). Predicting the clinical course of patients with inflammatory cardiomyopathy (iCMP) is difficult, and the prognostic value of current biological markers remains controversial. We tested whether expression of selected microRNAs in endomyocardial biopsies (EMBs) is related to LV functional recovery and clinical events in iCMP patients. METHODS AND RESULTS: EMBs were obtained from patients with iCMP (n = 76) and non-inflammatory DCM (n = 22)...
June 13, 2016: European Journal of Heart Failure
Bianca C Bernardo, Jenny Y Y Ooi, Aya Matsumoto, Yow Keat Tham, Saloni Singla, Helen Kiriazis, Natalie L Patterson, Junichi Sadoshima, Susanna Obad, Ruby C Y Lin, Julie R McMullen
microRNA-34a (miR-34a) is elevated in the diseased heart in mice and humans. Previous studies have shown that inhibiting miR-34a in male mice in settings of pathological cardiac hypertrophy or ischemia protects the heart against progression to heart failure. Whether inhibition of miR-34a protects the female heart is unknown. Furthermore, the therapeutic potential of silencing miR-34a in settings of dilated cardiomyopathy (DCM) and atrial fibrillation (AF) had not previously been assessed. In the present study, we examined the effect of silencing miR-34a in males and females in 1) a model of moderate DCM and 2) a model of severe DCM with AF...
June 8, 2016: Journal of Physiology
Juan Wang, Oi Wah Liew, Arthur Mark Richards, Yei-Tsung Chen
MicroRNAs (miRNAs) are non-coding RNAs that play essential roles in modulating the gene expression in almost all biological events. In the past decade, the involvement of miRNAs in various cardiovascular disorders has been explored in numerous in vitro and in vivo studies. In this paper, studies focused upon the discovery of miRNAs, their target genes, and functionality are reviewed. The selected miRNAs discussed herein have regulatory effects on target gene expression as demonstrated by miRNA/3' end untranslated region (3'UTR) interaction assay and/or gain/loss-of-function approaches...
2016: International Journal of Molecular Sciences
Xiaoping Lin, Steven Steinberg, Suresh K Kandasamy, Junaid Afzal, Blaid Mbiyangandu, Susan E Liao, Yufan Guan, Celia P Corona-Villalobos, Scot J Matkovich, Neal Epstein, Dotti Tripodi, Zhaoxia Huo, Garry Cutting, Theodore P Abraham, Ryuya Fukunaga, M Roselle Abraham
MicroRNAs (miRNAs) are recognized as important regulators of cardiac development, hypertrophy and fibrosis. Recent studies have demonstrated that genetic variations which cause alterations in miRNA:target interactions can lead to disease. We hypothesized that genetic variations in miRNAs that regulate cardiac hypertrophy/fibrosis might be involved in generation of the cardiac phenotype in patients diagnosed with hypertrophic cardiomyopathy (HCM). To investigate this question, we Sanger sequenced 18 miRNA genes previously implicated in myocyte hypertrophy/fibrosis and apoptosis, using genomic DNA isolated from the leukocytes of 199 HCM patients...
2016: PloS One
Peng Deng, Ling Chen, Zheng Liu, Ping Ye, Sihua Wang, Jie Wu, Yufeng Yao, Yuan Sun, Xiaofan Huang, Linyun Ren, Anchen Zhang, Ke Wang, Chuangyan Wu, Zhang Yue, Xuezeng Xu, Manhua Chen
BACKGROUND/AIMS: Cardiac fibrosis is the primary cause of deteriorated cardiac function in various cardiovascular diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are critical regulators of myocardial fibrosis. Specifically, many studies have reported that miR-150 is downregulated in cardiovascular diseases, such as acute myocardial infarction (AMI), myocardial hypertrophy and myocardial fibrosis. However, the exact role of miR-150 in these pathological processes remains unknown...
2016: Cellular Physiology and Biochemistry
Mian Cheng, Gang Wu, Yue Song, Lin Wang, Ling Tu, Lizhi Zhang, Cuntai Zhang
UNLABELLED: Backgroud: Myocardial fibrosis results in myocardial remodelling and dysfunction. Celastrol, a traditional oriental medicine, has been suggested to have cardioprotective effects. However, its underlying mechanism is unknown. This study investigated the ability of celastrol to prevent cardiac fibrosis and dysfunction and explored the underlying mechanisms. METHODS: Animal and cell models of cardiac fibrosis were used in this study. Myocardial fibrosis was induced by transverse aortic constriction (TAC) in mice...
2016: Cellular Physiology and Biochemistry
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