Plasma microRNAs serve as potential biomarkers for abdominal aortic aneurysm

Zhang, Wenwen; Shang, Tao; Huang, Chengdu; Yu, Tong; Liu, Chen; Qiao, Tong; Huang, Dian; Liu, Zhao; Liu, Changjian

doi:10.1016/j.clinbiochem.2015.04.016

Cited by 57 publications

(52 citation statements)

References 21 publications

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“…All samples were carefully selected for full term singleton pregnancies, non-complicated by maternal health conditions such as infection, which was necessary in reducing inter-sample variability. We observed that most of the up-regulated miRs regulated genes relevant to hypoxia responses [35–39], vascular disease [40–44], metabolism [45–49], inflammation [50–51], or were previously reported in pre-eclamptic placentas [52–55]. In contrast, the down-regulated miRs were for the most part relevant for genes with a role in obesity or cancers [56–58], though several had also been reported in association with pregnancy disorders involving placental insufficiency [52, 55,59–61].…”

Section: Resultsmentioning

confidence: 99%

Differential microRNA expression in human placentas of term intra-uterine growth restriction that regulates target genes mediating angiogenesis and amino acid transport

et al. 2017

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Placental insufficiency leading to intrauterine growth restriction (IUGR) demonstrates perturbed gene expression affecting placental angiogenesis and nutrient transfer from mother to fetus. To understand the post-transcriptional mechanisms underlying such placental gene expression changes, our objective was to identify key non-coding microRNAs that express biological function. To this end, we initially undertook microarrays targeting microRNAs in a small sub-set of placentas of appropriate (AGA) versus small for gestational age (SGA) weight infants, and observed up-regulation of 97 miRs and down-regulation of 44 miRs in SGA versus AGA. In a larger cohort of samples (AGA, n = 21; SGA, n = 11; IUGR subset, n = 5), we validated by qRT-PCR differential expression of three specific microRNAs (miR-10b, -363 and -149) that target genes mediating angiogenesis and nutrient transfer. Validation yielded an increase in miR-10b and -363 expression of ~2.5-fold (p<0.02 each) in SGA versus AGA, and of ~3-fold (p<0.005) in IUGR versus AGA, with no significant change despite a trending increase in miR-149. To further establish a cause-and-effect paradigm, employing human HTR8 trophoblast cells, we assessed the effect of nutrient deprivation on miR expression and inhibition of endogenous miRs on target gene expression. In-vitro nutrient deprivation (~50%) increased the expression of miR-10b and miR-149 by 1.5-fold (p<0.02) while decreasing miR-363 (p<0.0001). Inhibition of endogenous miRs employing antisense sequences against miR-10b, -363 and -149 revealed an increase respectively in the expression of the target genes KLF-4 (transcription factor which regulates angiogenesis), SNAT1 and 2 (sodium coupled neutral amino acid transporters) and LAT2 (leucine amino acid transporter), which translated into a similar change in the corresponding proteins. Finally to establish functional significance we performed dual-luciferase reporter assays with 3’-insertion of miR-10b alone and observed a ~10% reduction in the 5’-luciferase activity versus the control. Lastly, we further validated by microarray and employing MirWalk software that the pathways and target genes identified by differentially expressed miRs in SGA/IUGR compared to AGA are consistent in a larger cohort. We have established the biological significance of various miRs that target common transcripts mediating pathways of importance, which are perturbed in the human IUGR placenta.

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Section: Resultsmentioning

confidence: 99%

Differential microRNA expression in human placentas of term intra-uterine growth restriction that regulates target genes mediating angiogenesis and amino acid transport

et al. 2017

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“…[24–25] MiRNA-let-7b was also found decreased in plasma of patients with another type of aneurysm (abdominal aortic aneurysms) [26] although again these results were not confirmed in two comparable other studies. [27–28] Besides these three studies on miRNAs levels in IA tissue,[24–25] we identified two previous studies also analyzing miRNAs in blood of patients with IA.…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNAs in patients with intracranial aneurysms

et al. 2017

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IntroductionWe compared circulating microRNA (miRNA) levels in plasma of patients with intracranial aneurysms (IA) to those of controls as a first step towards finding potential biomarkers for individuals at high risk of IA development and its subsequent rupture.Patients and methodsUsing a PCR array we measured 370 miRNAs in plasma of 15 patients with prior aneurysmal subarachnoid hemorrhage (aSAH), of whom 11 had an additional unruptured IA (UIA), and of 15 controls. MiRNAs with a difference in levels with an absolute fold change (FC) > 1.2 and p<0.01 were further tested using real-time (RT) PCR in an additional independent set of 15 aSAH patients, 15 untreated UIA patients and 15 controls for replication (absolute FC >1.2 and p<0.05). We used receiver operating characteristic (ROC) curves to illustrate the diagnostic potential of these miRNAs.ResultsThree of five miRNAs with a difference in levels in the PCR array study were replicated with miRNA-183-5p decreased in all patients (FC = -2.2, p = 1.7x10-3), miRNA-200a-3p increased in aSAH patients (FC = 1.8, p = 2.8x10-2) and miRNA-let7b-5p decreased in UIA patients (FC = -1.7, p = 1.27x10-3) as compared to controls. In distinguishing aSAH patients from controls, the area under the ROC curve (AUC) was 0.80 (95% confidence interval (95% CI) 0.63–0.97) for miRNA-183-5p, and 0.74 (95% CI 0.55–0.94) for miRNA-200a-3p. In distinguishing untreated UIA patients from controls, AUC was 0.83 (95% CI 0.69–0.98) for miRNA-183-5p and 0.92 (95% CI 0.81–1) for miRNA-let-7b.Discussion/ConclusionsWe identified three specific circulating miRNAs that are able to discriminate between IA patients and controls. Follow-up studies should assess if these miRNAs may be used biomarkers for identifying individuals at high risk of IA development and its subsequent rupture.

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“…Zhang et al identified increased expression of miR-191-3p, -455-3p, and -1281 in the whole blood of AAA patients compared to controls, while a separate study showed decreased expression of miR-126, -124a, -146a, -155, -223, -29b, -15a, and -15b in AAA [164, 165]. Stather et al reported reduced expression of let-7e, miR-15a, and -196b in the peripheral blood of AAA patients and increased expression of miR-411 as compared to controls [165].…”

Section: Epigenetic Risk Factorsmentioning

confidence: 99%

Genetic and Epigenetic Regulation of Aortic Aneurysms

Kim

Stansfield

2017

BioMed Research International

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Aneurysms are characterized by structural deterioration of the vascular wall leading to progressive dilatation and, potentially, rupture of the aorta. While aortic aneurysms often remain clinically silent, the morbidity and mortality associated with aneurysm expansion and rupture are considerable. Over 13,000 deaths annually in the United States are attributable to aortic aneurysm rupture with less than 1 in 3 persons with aortic aneurysm rupture surviving to surgical intervention. Environmental and epidemiologic risk factors including smoking, male gender, hypertension, older age, dyslipidemia, atherosclerosis, and family history are highly associated with abdominal aortic aneurysms, while heritable genetic mutations are commonly associated with aneurysms of the thoracic aorta. Similar to other forms of cardiovascular disease, family history, genetic variation, and heritable mutations modify the risk of aortic aneurysm formation and provide mechanistic insight into the pathogenesis of human aortic aneurysms. This review will examine the relationship between heritable genetic and epigenetic influences on thoracic and abdominal aortic aneurysm formation and rupture.

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Plasma microRNAs serve as potential biomarkers for abdominal aortic aneurysm

Cited by 57 publications

References 21 publications

Differential microRNA expression in human placentas of term intra-uterine growth restriction that regulates target genes mediating angiogenesis and amino acid transport

Differential microRNA expression in human placentas of term intra-uterine growth restriction that regulates target genes mediating angiogenesis and amino acid transport

Circulating microRNAs in patients with intracranial aneurysms

Genetic and Epigenetic Regulation of Aortic Aneurysms

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