Tanshinone IIA Inhibits miR-1 Expression through p38 MAPK Signal Pathway in Post-infarction Rat Cardiomyocytes

Zhang, Yong; Zhang, Li; Chu, Wenfeng; Wang, Bing; Zhang, Jialin; Zhao, Ming; Li, Xuelian; Li, Baoxin; Lu, Yanjie; Yang, Baofeng; Shan, Hongli

doi:10.1159/000324012

Cited by 81 publications

(75 citation statements)

References 33 publications

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“…Moreover, propranolol inhibited the beta-adrenoceptor-cAMP-PKA signaling pathway and suppressed SRF expression and partially produced beneficial effects by down-regulating [40]. Furthermore, Tanshinone IIA could inhibit miR-1 expression by inhibiting activated p38 MAPK and heart special transcription factors, SRF and MEF2, in ischemic and hypoxic cardiomyocytes [41]. Therefore, miR-1 was a key molecule in the development of ventricular arrhythmias, which was emphasized in the current study.…”

Section: Discussionmentioning

confidence: 59%

Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

Sun

Zhao

et al. 2017

Cell Physiol Biochem

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Background/Aims: High-fat diet (HFD) causes cardiac electrical remodeling and increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an anthraquinone component isolated from rhubarb and has a similar chemical structure with emodin. The protective effect of emodin against cardiac diseases has been reported in the literature. However, the cardioprotective property of AE is still unknown. The present study investigated the effect of AE on HFD-induced QT prolongation in rats. Methods: Adult male Wistar rats were randomly divided into three groups: control, HFD, and AE-treatment groups. Normal diet was given to rats in the control group, high-fat diet was given to rats in HFD and AE-treatment groups for a total of 10 weeks. First, HFD rats and AE-treatment rats were fed with high-fat diet for 4 weeks to establish the HFD model. Serum total cholesterol and triglyceride levels were measured to validate the HFD model. Afterward, AE-treatment rats were intragastrically administered with 100 mg/kg AE each day for 6 weeks. Electrocardiogram monitoring and whole-cell patch-clamp technique were applied to examine cardiac electrical activity, action potential and inward rectifier K + current (I K1 ), respectively. Neonatal rat ventricular myocytes (NRVMs) were subjected to cholesterol and/or AE. Protein expression of Kir2.1 was detected by Western blot and miR-1 level was examined by real-time PCR in vivo and in vitro, respectively. Results: In vivo, AE significantly shortened the QT interval, action potential duration at 90% repolarization (APD 90 ) and resting membrane potential (RMP), which were markedly elongated by HFD. AE increased I K1 current and Kir2.1 protein expression which were reduced in HFD rats. Furthermore, AE significantly inhibited pro-arrhythmic miR-1 in the hearts of HFD rats. In vitro, AE decreased miR-1 expression levels resulting in an increase of Kir2.1 protein levels in cholesterol-enriched NRVMs. Conclusions: AE prevents HFD-induced QT prolongation by repressing miR-1 and upregulating its target Kir2.1. These findings suggest a novel pharmacological role of AE in HFD-induced cardiac electrical remodeling.

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Section: Discussionmentioning

confidence: 59%

Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

Sun

Zhao

et al. 2017

Cell Physiol Biochem

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“…Undoubtedly all these data supported that the structural and functional protection of LBPs on Tg mouse hearts was due largely to the down‐regulation of miR‐1 level and subsequent restoration of target proteins essential for cardiac contractile function. Other studies found that tanshinone IIA, an active component of a traditional Chinese medicine based on Salvia Miltiorrhiza, protected against arrhythmogenesis after myocardial infarction and cardiac sudden death induced by lethal arrhythmias via repression of miR‐1,8, 13 and Propranolol exerted ischaemic cardioprotection related to down‐regulation of miR‐1,7 providing powerful supports for our cardioprotective result of LBPs on HF by down‐regulation of miR‐1. These findings not only help us understand the mechanisms underlying the beneficial effects of LBPs on HF, but also conceptually advance our view regarding miRNAs to serve as potential therapeutic drug targets.…”

Section: Discussionmentioning

confidence: 71%

Lycium barbarum polysaccharides restore adverse structural remodelling and cardiac contractile dysfunction induced by overexpression of microRNA‐1

Zhang

Niu

et al. 2018

J Cellular Molecular Medi

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MicroRNA‐1 (miR‐1) stands out as the most prominent microRNA (miRNA) in regulating cardiac function and has been perceived as a new potential therapeutic target. Lycium barbarum polysaccharides (LBPs) are major active constituents of the traditional Chinese medicine based on L. barbarum. The purpose of this study was to exploit the cardioprotective effect and molecular mechanism of LBPs underlying heart failure. We found that LBPs significantly reduced the expression of myocardial miR‐1. LBPs improved the abnormal ECG and indexes of cardiac functions in P‐V loop detection in transgenic (Tg) mice with miR‐1 overexpression. LBPs recovered morphological changes in sarcomeric assembly, intercalated disc and gap junction. LBPs reversed the reductions of CaM and cMLCK, the proteins targeted by miR‐1. Similar trends were also obtained in their downstream effectors including the phosphorylation of MLC2v and both total level and phosphorylation of CaMKII and cMyBP‐C. Collectively, LBPs restored adverse structural remodelling and improved cardiac contractile dysfunction induced by overexpression of miR‐1. One of the plausible mechanisms was that LBPs down‐regulated miR‐1 expression and consequently reversed miR‐1‐induced repression of target proteins relevant to myocardial contractibility. LBPs could serve as a new, at least a very useful adjunctive, candidate for prevention and therapy of heart failure.

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“…Tanshinone ⅡA was shown to relieve ischemia-induced injury, decrease the elevated miR-1 levels in ischemic and hypoxic cardiomyocytes, and consequently restored the normal level of the miR-1 target Cx43. In ischemic and hypoxic cardiomyocytes, tanshinone ⅡA also inhibited activated p38 MAPK, SRF and MEF2 [92] .…”

Section: Therapeutic Opportunitiesmentioning

confidence: 92%

miRNome in myocardial infarction: Future directions and perspective

Boštjančič

Glavač

2014

WJC

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MicroRNAs (miRNAs), which are small and non-coding RNAs, are genome encoded from viruses to humans. They contribute to various developmental, physiological and pathological processes in living organisms. A huge amount of research results revealed that miRNAs regulate these processes also in the heart. miRNAs may have cell-type-specific or tissue-specific expression patterns or may be expressed ubiquitously. Primary studies of miRNA involvement in hypertrophy, heart failure and myocardial infarction analyzed miRNAs that are enriched in or specific for cardiomyocytes; however, growing evidence suggest that other miRNAs, not cardiac or muscle-specific, play a significant role in cardiovascular disease. Abnormal miRNA regulation has been shown to be involved in cardiac diseases, suggesting that miRNAs might affect cardiac structure and function. In this review, we focus on miRNAs that have been found to contribute to the pathogenesis of myocardial infarction (MI) and the response post-MI and characterized as diagnostic, prognostic and therapeutic targets. The majority of these studies were performed using mouse and rat models of MI, with a focus on the identification of basic cellular and molecular pathways involved in MI and in the response post-MI. Much research has also been performed on animal and human plasma samples from MI individuals to identify miRNAs that are possible prognostic and/or diagnostic targets of MI and other MI-related diseases. A large proportion of research is focused on miRNAs as promising therapeutic targets and biomarkers of drug responses and/or stem cell treatment approaches. However, only a few studies have described miRNA expression in human heart tissue following MI.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: MicroRNAs; Myocardial infarction; Human; Animal models; Biomarkers and targets Core tip: MicroRNAs (miRNAs) contribute to various developmental, physiological and pathological processes in the heart. Cardiac diseases show abnormal miRNA regulation. Primary studies of miRNA involvement in cardiac disease analyzed mainly miRNAs that enriched in or specific for cardiomyocytes; however, growing evidence suggests that other cell-type-specific or ubiquitously expressed miRNAs are also involved in cardiovascular disease. miRNAs were found to contribute to the pathogenesis of myocardial infarction (MI) and post-MI. The majority of studies focused on miRNAs in animal models of MI, in human and animal plasma samples of MI (prognostic and diagnostic targets), and on miRNAs as promising therapeutic targets.Boštjančič E, Glavač D. miRNome in myocardial infarction: Future directions and perspective. World J Cardiol 2014; 6(9): 939-958 Available from:

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Tanshinone IIA Inhibits miR-1 Expression through p38 MAPK Signal Pathway in Post-infarction Rat Cardiomyocytes

Cited by 81 publications

References 33 publications

Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

Lycium barbarum polysaccharides restore adverse structural remodelling and cardiac contractile dysfunction induced by overexpression of microRNA‐1

miRNome in myocardial infarction: Future directions and perspective

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