MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells

Liu, Dong; Yang, Pengyuan; Xiong, Qinghui; Song, Xuhui; Yang, Xiangqun; Liu, Lin; Yuan, Wenjing; Rui, Yao-Cheng

doi:10.1097/hjh.0b013e32833a4922

Cited by 121 publications

(101 citation statements)

References 49 publications

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“…Of note, both miR-125b and miR-320b are expressed in VECs, and their expressions were regulated as a result of cellular signals or environmental cues. 35,36 The preliminary functional study suggested that the 2 miRNAs could influence several critical signal transduction pathways (Table 3), including the TGF-β pathway and apoptosis. The TGF-β pathway is commonly disrupted in atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

Huang

Lü

et al. 2014

Circ Cardiovasc Genet

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A cute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. 1 Multiple conventional risk factors and serum atherosclerotic biomarkers have been established for coronary heart disease (CHD). 2 However, advances in genomics and proteomics, especially gene-expression profiling using microarray and quantitative real-time polymerase chain reaction (qPCR), have promoted the generation of many novel molecular biomarkers for AMI with potential clinical values. 3,4 Recently, microRNAs (miRNAs) have attracted extensive interest in the field of cardiovascular diseases. 5 Clinical Perspective on p 198MiRNAs are short, endogenous, noncoding RNAs that regulate gene expressions at the posttranscriptional level by binding to the 3′-untranslated regions of their target mRNAs. 6,7 MiRNAs have now emerged as key regulators of cardiac growth, vascular development, and angiogenesis. 8,9 Recent studies demonstrated that miRNAs can be detected in circulating blood and may be useful as disease biomarkers. 10,11 The levels and identities of circulating miRNAs in cardiovascular diseases have been evaluated in a series of studies. For instance, levels of some vascular and inflammation-associated miRNAs were found to be significantly lower in the plasma of 67 patients with CHD when compared with controls, 12 and the cardiac-specific miRNA, miR-208a, was only detectable in 33 patients with AMI and not Background-Circulating microRNAs ( miRNAs) are emerging as novel disease biomarkers. We aimed to explore the association between circulating miRNAs and the occurrence of acute myocardial infarction (AMI) in Chinese populations. Methods and Results-In the discovery stage, the plasma of 20 patients with AMI and 20 controls were pooled respectively and profiled by massively parallel sequencing. Seventy-seven miRNAs showed differential expression. Selected miRNAs were validated in 178 patients with AMI and 198 controls using quantitative reverse transcriptase polymerase chain reaction assays and further replicated in 150 patients with AMI and 150 controls. Results suggest that miR-320b and miR-125b levels were significantly lower in patients with AMI than in controls in both validation populations (P<0.0001). Lower levels of miR-320b and miR-125b were associated with increased occurrence of AMI (adjusted odds ratio, 4.71; 95% confidence interval, 2.96-7.48 and odds ratio, 4.27; 95% confidence interval, 2.84-6.41, respectively). Addition of the 2 miRNAs to traditional risk factors led to a significant improvement in the area under the curve from 0.822 (95% confidence interval, 0.787-0.856) to 0.871 (95% confidence interval, 0.842-0.900), with a net reclassification improvement of 20.45% (P<0.0001) and an integrated discrimination improvement of 0.16 (P<0.0001) for patients with AMI. A functional study showed that miR-320b and miR-125b could regulate the expression profiles of genes enriched in several signal transduction pathways critical for coronary heart disease in human vascular endothelial cells. Conclusions-The...

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Section: Discussionmentioning

confidence: 99%

Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

Huang

Lü

et al. 2014

Circ Cardiovasc Genet

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“…MiRNA'ların ekspresyon seviyelerini takip etmek için Custom miScript miRNA PCR Array (Qiagen) kullanıldı. Daha önce yapılan çalışma-larda, hipertansiyon ile ilişkisi saptanmış miR-125a (14) ve miR-155 (15) çalışıldı. MiRNA'ların ekspresyon düzeylerini normalize etmek için RNU6B kullanıldı.…”

Section: Cdna Sentezi Ve Kantitatif Real-time Pcrunclassified

“…Yüksek derecede esnek olan damarlar artmış volüme fazla basınç değişikliği olmadan uyum sağlarken, yarı sertleşmiş damarlarda ise damar hacmindeki küçük artışlar basınçta büyük artışlara neden olur. Vasküler mekanizmalardaki bu değişimlerin HT etyopatogenezindeki rolü ile ilişkili birtakım miRNA'larla (miR-143, miR-21, miR-221 ve miR-222) yapılmış çalışmalar da mevcuttur (14,20) .…”

Section: İstatistiksel Hesapunclassified

“…Li ve arkadaşları-nın sıçanlarda yaptığı bir çalışmada, hipertansiyonu olan sıçanlarda miR-125a ekspresiyonunun azaldığı ve endotelin-1 ekspresyonuyla ters ilişkili olduğunu göstermiştir (14) . Pulmoner hipertansiyon üzerine yapılan bir çalışmada hipoksik pulmoner hipertansiyonlu sıçanların akciğer dokusunda hipoksik olmayan sıçanlardakilere kıyasla miR-125a ekspresyon seviyelerinin daha yüksek olduğu bulunmuş.…”

Section: İstatistiksel Hesapunclassified

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The Investigation of MiR-125a and MiR-155 Levels in White Coat Hypertension and Essential Hypertension

Yavuzer¹,

Ali²,

Yeşilova³

et al. 2017

Okmeydani Medical Journal

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“…1B (miR-648, miR-517B, and miR-934). In addition, we included miR-125a-3p, miR-125a-5p, and miR-125b, since these miRNAs are reported to be involved in oxidized lowdensity lipoprotein-mediated regulation of ET-1 mRNA in vascular endothelial cells (33). Lastly, we included miR-199a since the stability of HIF-1␣ mRNA is affected by miR-199a in response to ethanol (34).…”

Section: Quantitation Of Transcripts By Semiquantitative Reverse Tranmentioning

confidence: 99%

MicroRNA 648 Targets ET-1 mRNA and Is Cotranscriptionally Regulated with MICAL3 by PAX5

Gonsalves

Mpollo

et al. 2015

Molecular and Cellular Biology

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c Pulmonary hypertension (PHT) is associated with high mortality in sickle cell anemia (SCA). Previously, we showed that elevated levels of placenta growth factor (PlGF) in SCA patients correlate with increased levels of the potent vasoconstrictor endothelin-1 (ET-1) and PHT. Moreover, PlGF induced the expression of ET-1 via hypoxia-inducible factor 1␣. Here, we show a novel example of ET-1 posttranscriptional regulation by PlGF via action of microRNA 648 (miR-648), which is subject to transcriptional coregulation with its host gene, MICAL3 (microtubule-associated monooxygenase, calponin, and LIM domain containing 3gene). PlGF repressed expression of miR-648 in endothelial cells. Luciferase reporter assays using wild-type and mutant ET-1 3= untranslated region (UTR) constructs, and transfection of miR-648 mimics showed that miR-648 targets the 3= UTR of ET-1 mRNA. Since miR-648 is located in a 5=-proximal intron of MICAL3, we examined which of three potential promoters was responsible for its expression. The MICAL3 distal promoter (P1) was the predominant promoter used for transcription of premiR-648, and it was under positive control by PAX5 (paired box protein 5) transcription factor, as demonstrated by the loss and gain of function of PAX5 activity, and chromatin immunoprecipitation analysis. These studies provide a novel link wherein PlGF-mediated downregulation of PAX5 attenuates miR-648 expression leading to increased ET-1 levels that are known to induce PHT in SCA. Endothelin-1 (ET-1), a 21-amino-acid peptide hormone primarily synthesized and secreted by endothelium in vivo, is involved in proliferation of smooth muscle cells and vascular tone (1-4). In the vasculature, the endothelin system, comprising endothelin ligands (ET-1, ET-2, and ET-3), endothelin receptors (ET-AR and ET-BR), and two activating peptidases, has a basal vasoconstricting role; dysfunction contributes to the development of diseases such as hypertension and other cardiovascular diseases (3). Hypoxia is a potent inducer of ET-1 gene expression in endothelial cells via activation of hypoxia-inducible factor 1␣ (HIF-1␣) (5, 6).Pulmonary hypertension (PHT), occurs in ca. 10% of adults with sickle cell anemia (SCA), and its diagnosis is associated with a 38 to 40% mortality at 2 to 6 years (7,8). Sickle mice develop PHT with increasing age, manifested as high pulmonary artery pressures and right ventricular hypertrophy (9). Physiological factors implicated in PHT in SCA include endothelial dysfunction, pulmonary vasoconstriction, and vascular remodeling, all of which are associated with chronic hemolysis, hypoxia, hemostatic activation, and inflammation (8, 10-12). ET-1 and nitric oxide (NO) are mutually opposing pulmonary vasoactive factors that regulate pulmonary vascular tone. It is postulated that hemolysis leads to quenching of NO by extracellular/cell-free hemoglobin, thereby reducing NO bioavailability (11, 13), which in turn leads to the clinical manifestations of sickle PHT (13-15). Numerous studies in SCA and other hemolytic anem...

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MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells

Abstract: Our finding demonstrated that endothelial miR-125a/b-5p inhibits ET-1 expression in VECs, which revealed a novel miRNA-mediated mechanism in vasomotor homeostasis.

Cited by 121 publications

References 49 publications

Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

The Investigation of MiR-125a and MiR-155 Levels in White Coat Hypertension and Essential Hypertension

MicroRNA 648 Targets ET-1 mRNA and Is Cotranscriptionally Regulated with MICAL3 by PAX5

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