Role of MicroRNA in Endothelial Dysfunction and Hypertension

Nemecz, Miruna; Alexandru, Nicoleta; Tanko, Gabriela

doi:10.1007/s11906-016-0696-8

Cited by 96 publications

(74 citation statements)

References 160 publications

(187 reference statements)

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“…The mature miRNAs can repress post‐transcriptional level of gene expression by binding to complementary sequences located on the 3′ untranslated region (3′UTR) of their target specific messenger RNAs (mRNAs) 3. Increasing evidence suggest a significant role of miRNAs as mediators in vascular ageing and inflammatory process in animal models and human studies 4, 5. To date, several miRNAs have been identified to regulate the process of endothelial senescence and inflammation, such as miR‐217,6 miR‐34a,7 miR‐146a8, 9 and miR‐181b 10.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐216a induces endothelial senescence and inflammation via Smad3/IκBα pathway

Yang

Chen

et al. 2018

J Cellular Molecular Medi

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Vascular endothelial senescence contributes to atherosclerosis and coronary artery disease (CAD), but the mechanisms are yet to be clarified. We identified that microRNA‐216a (miR‐216a) significantly increased in senescent endothelial cells. The replicative senescence model of human umbilical vein endothelial cells (HUVECs) was established to explore the role of miR‐216a in endothelial ageing and dysfunction. Luciferase assay indicated that Smad3 was a direct target of miR‐216a. Stable expression of miR‐216a induced a premature senescence‐like phenotype in HUVECs with an impairment in proliferation and migration and led to an increased adhesion to monocytes by inhibiting Smad3 expression and thereafter modulating the degradation of NF‐κB inhibitor alpha (IκBα) and activation of adhesion molecules. Conversely, inhibition of endogenous miR‐216a in senescent HUVECs rescued Smad3 and IκBα expression and inhibited monocytes attachment. Plasma miR‐216a was significantly higher in old CAD patients (>50 years) and associated with increased 31% risk for CAD (odds ratio 1.31, 95% confidence interval 1.03‐1.66; P = .03) compared with the matched healthy controls (>50 years). Taken together, our data suggested that miR‐216a promotes endothelial senescence and inflammation as an endogenous inhibitor of Smad3/IκBα pathway, which might serve as a novel target for ageing‐related atherosclerotic diseases.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‐216a induces endothelial senescence and inflammation via Smad3/IκBα pathway

Yang

Chen

et al. 2018

J Cellular Molecular Medi

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“…In addition to ART-associated DNA methylation and chromatin acetylation modifications, the role of noncoding RNAs in regulating gene expression has become a concern in IVF-ET offspring [36]. It is known that multiple microRNAs (miRNAs) are involved in the regulation of hypertension, coronary heart disease, and glycolipid metabolic disorders [37,38]. However, few studies have focused on whether ART affects the expression of miRNAs.…”

Section: Introductionmentioning

confidence: 99%

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Wang

Zhang

Fang

et al. 2018

Biology of Reproduction

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Epidemiological studies have revealed that offspring conceived by in vitro fertilization (IVF) have an elevated risk of cardiovascular malformations at birth, and are more predisposed to cardiovascular diseases. The renin-angiotensin system (RAS) plays an essential role in both the pathogenesis of congenital heart disease in fetuses and cardiovascular dysfunction in adults. This study aimed to assess the relative expression levels of genes in the RAS pathway in mice conceived using IVF, compared to natural mating with superovulation. Results demonstrated that expression of the angiotensin II receptor type 1 (AGTR1), connective tissue growth factor (CTGF), and collagen 3 (COL3), in the myocardial tissue of IVF-conceived mice, was elevated at 3 weeks, 10 weeks, and 1.5 years of age, when compared to their non-IVF counterparts. These data were supported by microRNA microarray analysis of the myocardial tissue of aged IVF-conceived mice, where miR-100, miR-297, and miR-758, which interact with COL3, AGTR1, and COL1 respectively, were upregulated when compared to naturally mated mice of the same age. Interestingly, bisulfite sequencing data indicated that IVF-conceived mice exhibited decreased methylation of CpG sites in Col1. In support of our in vivo investigations, miR-297 overexpression was shown to upregulate AGTR1 and CTGF, Effects of in vitro fertilization on myocardium, 2018, Vol. 99, No. 6 1277 and increased cell proliferation in cultured H9c2 cardiomyocytes. These findings indicate that the altered expression of RAS in myocardial tissue might contribute to cardiovascular malformation and/or dysfunction in IVF-conceived offspring. Furthermore, these cardiovascular abnormalities might be the result of altered DNA methylation and abnormal regulation of microRNAs. Summary SentenceAltered expression of the renin-angiotensin system in myocardial tissue might contribute to an increased risk of cardiovascular malformations and dysfunction in IVF offspring, and is involved in abnormal regulations of DNA methylation and microRNAs.

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“…Clinically, patients with systemic diseases are common, and some studies have pointed out that some miRNA also play an important role in the development of some systemic diseases. [44][45][46] In addition, this study did not include studies on African ethnicity alone, and the included studies were all positive, which may bias the interpretation of the results, so more large-scale research and better four or more miRNA combination are needed in the use of validating our conclusions for early LC and even high-risk populations of LC.…”

Section: Discussionmentioning

confidence: 99%

Could microRNA be used as a diagnostic tool for lung cancer?

Wang

Guan

Wang

2019

J of Cellular Biochemistry

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Objectives Current methods for diagnosing lung cancer (LC) have varying degrees of risks and complications. MicroRNA (miRNA) is a small molecule noncoding RNA with gene regulation functions. Many studies have shown that miRNA can be used for the diagnosis of LC, but there are differences in diagnostic accuracy. Therefore, we aim to systematically review and meta‐analyze published articles to comprehensively evaluate the diagnostic value of miRNA for LC. Materials and methods We searched the PubMed, Embase, and Cochrane databases, and calculated the area under the curve (AUC) by plotting the summary receiver operator characteristic curve using the sensitivity and specificity of each included study. The AUC was calculated and the likelihood ratio was plotted to assess the diagnostic accuracy of miRNA. We used QUADAS‐2 in Review Manager 5.3 to evaluate the quality of all the articles. The other analyses were performed using the STATA 12.0 software. Results We included a total of 29 articles, 98 studies, and the qualities of all the articles were satisfactory. The overall pooled parameters calculated from all studies were as follows: sensitivity = 0.77, specificity = 0.83, positive likelihood ratio (PLR) = 4.6, negative likelihood ratio (NLR) = 0.28, and AUC = 0.87 for miRNA diagnosis. It had significant advantages over other biomarkers. Subgroup analysis showed that when combined four or more miRNA for the diagnosis of LC, the parameters were as follows: sensitivity = 0.90, specificity = 0.93, PLR = 13.2, NLR = 0.11, and AUC = 0.97. Conclusion Four or more miRNA combination could be used for the diagnosis of LC. Besides this, we also found that miRNA showed a greater advantage in distinguishing LC from benign lung diseases than distinguishing between LC and normal people. Our findings provided a new way of thinking about the clinical diagnosis of LC from a nonmorphological aspect.

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Role of MicroRNA in Endothelial Dysfunction and Hypertension

Cited by 96 publications

References 160 publications

MicroRNA‐216a induces endothelial senescence and inflammation via Smad3/IκBα pathway

MicroRNA‐216a induces endothelial senescence and inflammation via Smad3/IκBα pathway

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Could microRNA be used as a diagnostic tool for lung cancer?

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