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MicroRNA cardiac fibrosis

Juan Xu, Haiqing Wu, Songwen Chen, Baozhen Qi, Genqing Zhou, Lidong Cai, Liqun Zhao, Yong Wei, Shaowen Liu
Atrial fibrosis serves as an important contributor to atrial fibrillation (AF). Recent data have suggested that microRNA-30c (miR-30c) is involved in fibrotic remodelling and cancer development, but the specific role of miR-30c in atrial fibrosis remains unclear. The purpose of this study was to investigate the role of miR-30c in atrial fibrosis and its underlying mechanisms through in vivo and in vitro experiments. Our results indicate that miR-30c is significantly down-regulated in the rat abdominal aortic constriction (AAC) model and in the cellular model of fibrosis induced by transforming growth factor-β1 (TGF-β1)...
March 13, 2018: Journal of Cellular and Molecular Medicine
Hongzhi Li, Yeming Xie, Yunshuang Liu, Yali Qi, Chong Tang, Xuefeng Li, Kuiyang Zuo, Dingce Sun, Yongchao Shen, Daxin Pang, Yanhhui Chu, Binghai Zhao
Heart failure arises from diverse cardiovascular diseases, including hypertension, ischemic disease and atherosclerosis, valvular insufficiency, myocarditis, and contractile protein mutations. MicroRNAs are dysregulated in heart failure, but identification of the specific microRNAs involved remains incomplete. Here, we evaluate miR-25 expression in the peripheral blood from healthy, dilated cardiomyopathy (DCM), remote infarct (OMI), hypertensive heart disease (HHD), and HHD resulting in heart failure (HHDF) using q-PCR...
February 27, 2018: Experimental Cell Research
Lu Zhang, Hongli Yin, Lei Jiao, Tianyi Liu, Yuqiu Gao, Yingchun Shao, Yuanyuan Zhang, Hongli Shan, Ying Zhang, Baofeng Yang
BACKGROUND/AIMS: Cardiac fibrosis is an important cardiac remodeling event that can ultimately lead to the development of severe arrhythmia and heart failure. MicroRNAs (miRNAs) are involved in the pathogenesis of many cardiovascular diseases. Here, we aimed to investigate the effects of caveolin-3 (Cav3) on the pathogenesis of cardiac fibrosis and the underlying molecular mechanisms. METHODS: Cav3 expression was decreased in cardiac fibrosis in vivo and in vitro model...
February 21, 2018: Cellular Physiology and Biochemistry
Wei Huang, Yuliang Feng, Jialiang Liang, Hao Yu, Cheng Wang, Boyu Wang, Mingyang Wang, Lin Jiang, Wei Meng, Wenfeng Cai, Mario Medvedovic, Jenny Chen, Christian Paul, W Sean Davidson, Sakthivel Sadayappan, Peter J Stambrook, Xi-Yong Yu, Yigang Wang
The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by the limited regeneration capacity of adult CMs, partially due to their withdrawal from the cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated in CMs during the postnatal switch from proliferation to terminal differentiation. In neonatal mice, cardiac-specific overexpression of miR-128 impairs CM proliferation and cardiac function, while miR-128 deletion extends proliferation of postnatal CMs by enhancing expression of the chromatin modifier SUZ12, which suppresses p27 (cyclin-dependent kinase inhibitor) expression and activates the positive cell cycle regulators Cyclin E and CDK2...
February 16, 2018: Nature Communications
Guanghong Jia, Michael A Hill, James R Sowers
Heart failure and related morbidity and mortality are increasing at an alarming rate, in large part, because of increases in aging, obesity, and diabetes mellitus. The clinical outcomes associated with heart failure are considerably worse for patients with diabetes mellitus than for those without diabetes mellitus. In people with diabetes mellitus, the presence of myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors, such as hypertension and dyslipidemia, has led to the descriptive terminology, diabetic cardiomyopathy...
February 16, 2018: Circulation Research
Bo Yu, Wei Li, Fen Al, Zhen Chen
Cardiac fibroblasts (CFBs) play pivotal roles in myocardial fibrosis, which is the leading cause of arrhythmia. This study was aimed to investigate the modulation of microRNA (miR)-33a on proliferation, apoptosis and fibrosis of human CFBs. CFBs were respectively transfected with miR-control, miR-33a mimic or miR-33a inhibitor, followed by induction of transforming growth factor-β (TGF-β). Non-treated CFBs acted as control. Cell viability, apoptosis, and fibrosis which reflected by expressions of Col-I, Col-III and α-smooth muscle actin (α-SMA) were evaluated by CCK-8 assay, flow cytometry, qRT-PCR and Western blot analysis...
August 1, 2017: Die Pharmazie
Jia Qiu, An Wang, Yingna Xu, Shigang Qiao, Jianzhong An, Hua Li, Chen Wang
OBJECTIVE: To investigate the role of microRNA-1 (miR-1) in cardiac fibroblasts induced by high glucose in rats. METHODS: The primary fibroblasts were cultured from the apical tissue of 1-3 day-old Sprague-Dawley (SD) rats. The cells which were passaged to generation 3 or 4, were randomly divided into normal glucose+lentivector-vehicle group (CON+Lv-Vehicle group), normal glucose+lentivector-miR-1 group (CON+Lv-miR1 group), high glucose+lentivector-vehicle group (HG+Lv-Vehicle group), high glucose+lentivector-miR-1 group (HG+Lv-miR1 group), high glucose+Lv-Vehicle+inhibitor group (HG+Lv-Vehicle+CC group), and high glucose+lentivector-miR-1+inhibitor group (HG+Lv-miR1+CC group)...
February 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Yue Ji, Ming Qiu, Yejiao Shen, Li Gao, Yaqing Wang, Wei Sun, Xinli Li, Yan Lu, Xiangqing Kong
MicroRNA (miRNA/miR) dysregulation has been reported to be fundamental in the development and progression of cardiac hypertrophy and fibrosis. In the present study, miR-327 levels in fibroblasts were increased in response to cardiac hypertrophy induced by transverse aortic constriction with prominent cardiac fibrosis, particularly when compared with the levels in unstressed cardiomyocytes. In neonatal rat cardiac fibroblasts, induced expression of miR-327 upregulated fibrosis-associated gene expression and activated angiotensin II-induced differentiation into myofibroblasts, as assessed via α-smooth muscle actin staining...
January 25, 2018: International Journal of Molecular Medicine
Scott W Ferguson, Jinli Wang, Christine J Lee, Maixian Liu, Sriram Neelamegham, John M Canty, Juliane Nguyen
Mesenchymal stem cell (MSC)-derived exosomes mediate tissue regeneration in a variety of diseases including ischemic heart injury, liver fibrosis, and cerebrovascular disease. Despite an increasing number of studies reporting the therapeutic effects of MSC exosomes, the underlying molecular mechanisms and their miRNA complement are poorly characterized. Here we microRNA (miRNA)-profiled MSC exosomes and conducted a network analysis to identify the dominant biological processes and pathways modulated by exosomal miRNAs...
January 23, 2018: Scientific Reports
Jingfeng Wang, Jingjing Zhang, Xuefeng Ding, Yanyan Wang, Zhiming Li, Weipeng Zhao, Jianguo Jia, Jingmin Zhou, Junbo Ge
MicroRNAs (miRNAs/miRs) serve a role as important regulators in cardiac hypertrophy. The present study aimed to reveal the differential expression profile of miRNAs between young and aging spontaneously hypertensive rats (SHRs) and studied the functional annotation of predicted targets. Briefly, 3‑month‑old and 12‑month‑old SHRs (n=3/group) were subjected to echocardiography, histopathological analysis and dihydroethidium staining. Subsequently, small RNA sequencing and data processing was conducted to identify the differentially expressed miRNAs between these two groups...
January 9, 2018: International Journal of Molecular Medicine
Renae Waters, Perwez Alam, Settimio Pacelli, Aparna R Chakravarti, Rafeeq P H Ahmed, Arghya Paul
The objective of this study was to develop an injectable and biocompatible hydrogel that can deliver a cocktail of therapeutic biomolecules (secretome) secreted by human adipose-derived stem cells (hASCs) to the peri-infarct myocardium. Gelatin and Laponite® were combined to formulate a shear-thinning, nanocomposite hydrogel (nSi Gel) as an injectable carrier of secretome (nSi Gel+). The growth factor composition and the pro-angiogenic activity of the secretome were tested in vitro by evaluating the proliferation, migration and tube formation of human umbilical endothelial cells...
December 24, 2017: Acta Biomaterialia
Dongtak Jeong, Jimeen Yoo, Philyoung Lee, Sacha V Kepreotis, Ahyoung Lee, Christine Wahlquist, Brian D Brown, Changwon Kho, Mark Mercola, Roger J Hajjar
MicroRNAs are promising therapeutic targets, because their inhibition has the potential to normalize gene expression in diseased states. Recently, our group found that miR-25 is a key SERCA2a regulating microRNA, and we showed that multiple injections of antagomirs against miR-25 enhance cardiac contractility and function through SERCA2a restoration in a murine heart failure model. However, for clinical application, a more stable suppressor of miR-25 would be desirable. Tough Decoy (TuD) inhibitors are emerging as a highly effective method for microRNA inhibition due to their resistance to endonucleolytic degradation, high miRNA binding affinity, and efficient delivery...
November 26, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Hironori Hara, Norifumi Takeda, Issei Komuro
Inflammatory and fibrotic responses to myocardial damage are essential for cardiac repair; however, these responses often result in extensive fibrotic remodeling with impaired systolic function. Recent reports have suggested that such acute phase responses provide a favorable environment for endogenous cardiac regeneration, which is mainly driven by the division of pre-existing cardiomyocytes (CMs). Existing CMs in mammals can re-acquire proliferative activity after substantial cardiac damage, and elements other than CMs in the physiological and/or pathological environment, such as hypoxia, angiogenesis, and the polarity of infiltrating macrophages, have been reported to regulate replication...
2017: Inflammation and Regeneration
Qiancheng Luo, Dongfeng Guo, Guorong Liu, Guo Chen, Min Hang, Mingming Jin
BACKGROUND/AIMS: Recent studies have indicated that exosomes play an important role in adipose-derived stem cell (ADSC) transplant-mediated ischaemic heart disease therapy. However, the treatment effect is not obvious. The aim of this study is to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-126 have a more protective effect on acute myocardial infarction (AMI). METHODS: Exosomes were characterized by transmission electron microscopy, and the exosome particles were further examined using nanoparticle tracking analyses...
2017: Cellular Physiology and Biochemistry
Johanna Heid, Chiara Cencioni, Roberto Ripa, Mario Baumgart, Sandra Atlante, Giuseppina Milano, Alessandro Scopece, Carsten Kuenne, Stefan Guenther, Valerio Azzimato, Antonella Farsetti, Giacomo Rossi, Thomas Braun, Giulio Pompilio, Fabio Martelli, Andreas M Zeiher, Alessandro Cellerino, Carlo Gaetano, Francesco Spallotta
The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5´methyl-cytosine (5mC) level decrease...
December 4, 2017: Scientific Reports
Yassine Sassi, Petros Avramopoulos, Deepak Ramanujam, Laurenz Grüter, Stanislas Werfel, Simon Giosele, Andreas-David Brunner, Dena Esfandyari, Aikaterini S Papadopoulou, Bart De Strooper, Norbert Hübner, Regalla Kumarswamy, Thomas Thum, Xiaoke Yin, Manuel Mayr, Bernhard Laggerbauer, Stefan Engelhardt
Chronic cardiac stress induces pathologic hypertrophy and fibrosis of the myocardium. The microRNA-29 (miR-29) family has been found to prevent excess collagen expression in various organs, particularly through its function in fibroblasts. Here, we show that miR-29 promotes pathologic hypertrophy of cardiac myocytes and overall cardiac dysfunction. In a mouse model of cardiac pressure overload, global genetic deletion of miR-29 or antimiR-29 infusion prevents cardiac hypertrophy and fibrosis and improves cardiac function...
November 20, 2017: Nature Communications
Y Asif, M E Wlodek, M J Black, A P Russell, P F Soeding, G D Wadley
The aim of this study was to investigate if endurance training during juvenile life 'reprograms' the heart and leads to sustained improvements in the structure, function, and morphology of the adult heart. Male Wistar Kyoto rats were exercise trained 5 days/week for four weeks in either juvenile (5-9 weeks of age), adolescent (11-15 weeks of age) or adult life (20-24 weeks of age). Juvenile exercise training, when compared to 24 week old sedentary rats, led to sustained increases in left ventricle (LV) mass (+18%; P < 0...
November 16, 2017: Journal of Physiology
Jinyun Zhu, Kai Lu, Ning Zhang, Yun Zhao, Qunchao Ma, Jian Shen, Yinuo Lin, Pingping Xiang, Yaoliang Tang, Xinyang Hu, Jinghai Chen, Wei Zhu, Keith A Webster, Jian'an Wang, Hong Yu
Hypoxia treatment enhances paracrine effect of mesenchymal stem cells (MSCs). The aim of this study was to investigate whether exosomes from hypoxia-treated MSCs (Exo(H)) are superior to those from normoxia-treated MSCs (Exo(N)) for myocardial repair. Mouse bone marrow-derived MSCs were cultured under hypoxia or normoxia for 24 h, and exosomes from conditioned media were intramyocardially injected into infarcted heart of C57BL/6 mouse. Exo(H) resulted in significantly higher survival, smaller scar size and better cardiac functions recovery...
November 16, 2017: Artificial Cells, Nanomedicine, and Biotechnology
Shuilian Luo, Yuhang Chen, Rui He, Yujun Shi, Li Su
OBJECTIVE: The decreased expression of muscle-specific microRNA-1 (miR-1) has been found in many cardiovascular diseases and is considered to contribute to heart failure (HF). Here we investigated the role of miR-1 in myocardium protection by infusion of miR-1 in a cardiac global miRNA-deficient mouse. METHODS: We generated a cardiac-selective miRNA-deficient mouse by crossing Dicer(flox/flox) mice with mice expressing tamoxifen-inducible Cre recombinase under the control of a mouse αMHC promoter...
November 5, 2017: Biochemical and Biophysical Research Communications
Li Li, Kelsey R Bounds, Piyali Chatterjee, Sudhiranjan Gupta
BACKGROUND: Cardiac fibrosis occurs because of disruption of the extracellular matrix network leading to myocardial dysfunction. Angiotensin II has been implicated in the development of cardiac fibrosis. Recently, microRNAs have been identified as an attractive target for therapeutic intervention in cardiac pathologies; however, the underlying mechanism of microRNAs in cardiac fibrosis remains unclear. MicroRNA-130a (miR-130a) has been shown to participate in angiogenesis and cardiac arrhythmia; however, its role in cardiac fibrosis is unknown...
November 7, 2017: Journal of the American Heart Association
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