Prediction of long-term outcome after acute myocardial infarction using circulating miR-145

Zhang

et al. 2017

Cell Physiol Biochem

Background/Aims: Myocardial infarction (MI) is a leading cause of morbidity and mortality. Here, we sought to explore the potential role and underlying mechanism of miR-145 in MI. Methods: H9c2 cells were cultured under persistent hypoxia to simulate MI. The hypoxia-induced injury was assessed on the basis of cell viability, migration, invasion and apoptosis. The expression of miR-145 was evaluated by qRT-PCR and the influence of aberrantly expressed miR-145 on H9c2 cells under hypoxia was also estimated. Utilizing bioinformatics methods, the target genes of miR-145 were verified by luciferase reporter assay. Then, effects of abnormally expressed target gene on miR-145 silenced H9c2 cells were assessed. Finally, the phosphorylation levels of key kinases in the phosphatidylinositol-3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways were detected by Western blot analysis. Results: Hypoxia remarkably lowered viability, migration and invasion but promoted cell apoptosis. Meantime, the miR-145 level was up-regulated in H9c2 cells under hypoxia. Following experiments suggested that hypoxia-induced injury was exacerbated by miR-145 overexpression while was alleviated by miR-145 silence. Rac1 was predicted and further validated to be a target gene of miR-145. The influence of miR-145 silencing on H9c2 cells under hypoxia could be reversed by down-regulation of Rac1. Additionally, the phosphorylation levels of PI3K, AKT, MAPK and ERK were all elevated in miR-145 silenced cells and these alterations were reversed by down-regulation of Rac1. Conclusion: miR-145 silencing could protect H9c2 cells against hypoxia-induced injury by targeting Rac1, in which PI3K/AKT and MAPK/ERK pathways might be involved.

Section: Discussionmentioning

confidence: 99%

MicroRNA-145 Aggravates Hypoxia-Induced Injury by Targeting Rac1 in H9c2 Cells

Zhang

et al. 2017

Cell Physiol Biochem

“…The seven selected studies 22,23,27,28,30,35,36 ( Table 5 ) did not identify miRs which significantly predicted long-term mortality; however, mid-term and short-term mortality could be predicted to a certain extent. …”

Section: Resultsmentioning

confidence: 96%

“…22 1053 (−); 102(+) a miR-133a, miR-208b, miR-223, miR-320a, miR-451, miR-499miR-208b (+)Unadjusted ROC (AUC: 95% CI) a :0.67: 0.52–0.81Dong et al . 23 224(−); 22(+) b miR-145miR-145 (+)Multivariate Cox regression(HR: 95% CI) b, c :5.63: 1.99–15.91, P = 0.0012Goretti et al . 27 446(−); 64(+) d miR-208b, miR-499–Multivariate linear regression d : ORs and 95% CI include 1He et al .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review

et al. 2016

The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide accurate prognosis for survival in, patients with atherosclerosis, coronary artery disease, and acute coronary syndrome (ACS). A systematic search of published original research yielded a total of 72 studies. After review of the risk of bias of the published studies, according to Cochrane Collaboration and the QUADUAS Group standards, 19 studies were selected. Overall 52 different miRs were reported. In particular, miR-133a/b (5 studies), miR-208a/b (6 studies), and miR-499 (7 studies) were well studied and found to be significant diagnostic and/or prognostic markers across different cardiovascular disease progression stages. miR-1 and miR-145b are potential biomarkers of ACS; miR-1 with higher sensitivity for all acute myocardial infarction (AMI), and miR-145 for STEMI and worse outcome of AMI. But when miRs were studied across different ACS study populations, patients had varying degrees of coronary stenosis, which was identified as an important confounder that limited the ability to quantitatively pool the study results. The identified miRs were found to regulate endothelial function and angiogenesis (miR-1, miR-133), vascular smooth muscle cell differentiation (miR-133, miR-145), communication between vascular smooth muscle and endothelial cell to stabilize plaques (miR-145), apoptosis (miR-1, miR-133, miR-499), cardiac myocyte differentiation (miR-1, miR-133, miR-145, miR-208, miR-499), and to repress cardiac hypertrophy (miR-133). Their role in these processes may be explained by regulation of shared RNA targets such as cyclin-dependent kinase inhibitor 1A (or p21), ETS proto-oncogene 1, fascin actin-bundling protein 1, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, insulin-like growth factor 1 receptor LIM and SH3 protein 1, purine nucleoside phosphorylase, and transgelin 2. These mechanistic data further support the clinical relevance of the identified miRs. miR-1, miR-133a/b, miR-145, miR-208a/b, and miR-499(a) in plasma and/or serum show some potential for diagnosis of cardiovascular disease. However, biased selection of miRs in most studies and unexplained contrasting results are major limitations of current miR research. Inconsistencies need to be addressed in order to definitively identify clinically useful miRs. Therefore, this paper presents important aspects to improve future miR research, including unbiased selection of miRs, standardization/normalization of reference miRs, adjustment for patient comorbidities and medication, and robust protocols of data-sharing plans that could prevent selective publication and selective reporting of miR research outcomes.

Experimental Physiology

“…miR‐150 limits atherogenesis by moderating immune cell activation and secretion of cytokines and enhances vascular health by promoting endothelial and endothelial progenitor cell function (Desjarlais, Dussault, Dhahri, Mathieu, & Rivard, ). Lower circulating levels of miR‐145 and miR‐150 have been linked with increased CVD risk and events (Dong et al., ; Rhodes et al., ). The lack of alteration in these miRNAs with insufficient sleep suggests a differential effect of sleep on circulating miRNA and demonstrates the complexity of the interaction of sleep and circadian physiology with miRNA regulation and, in turn, cellular function.…”

Section: Discussionmentioning

confidence: 99%

Insufficient sleep is associated with a pro‐atherogenic circulating microRNA signature

Hijmans

Levy

Garcia

et al. 2019

New Findings What is the central question of the studyIs habitual short sleep associated with altered circulating levels of specific inflammation‐ and vascular‐related microRNAs? What is the main finding and its importance?Circulating levels of miR‐125a, miR‐126 and miR‐146a were significantly lower in the short sleep compared with the normal sleep group. Altered circulating profiles of these vascular‐related microRNAs have been linked to vascular inflammation, dysfunction and increased cardiovascular disease events. Sleep‐related changes in these microRNAs are consistent with, and might play a role in, the aberrant vascular physiology and increased vascular risk associated with short sleep. Abstract Habitual short sleep duration (<7 h night−1) is associated with increased morbidity and mortality attributable, in large part, to increased inflammatory burden and endothelial dysfunction. MicroRNAs (miRNAs) play a key role in regulating vascular health, and circulating levels are now recognized to be sensitive and specific biomarkers of cardiovascular function, inflammation and disease. The aim of this study was to determine whether the expression of circulating miR‐34a, miR‐92a, miR‐125a, miR‐126, miR‐145, miR‐146a and miR‐150 is disrupted in adults who habitually sleep <7 h night−1 (short sleep). These were chosen based upon their well‐established links with vascular inflammation, function and, in turn, cardiovascular risk. Twenty‐four adults were studied: 12 with normal nightly sleep duration (six men and six women; age, 55 ± 3 years old; sleep duration, ≥7.0 h night−1) and 12 with short nightly sleep duration (seven men and five women; 55 ± 2 years old; sleep duration, <7 h night−1), and circulating miRNA expression was assayed by RT‐PCR. All subjects were non‐smokers, normolipidaemic, non‐medicated and free of overt cardiovascular disease. Circulating levels of miR‐125a (3.07 ± 1.98 versus 7.34 ± 5.34 a.u.), miR‐126 [1.28 (0.42–2.51) versus 1.78 (1.29–4.80) a.u.] and miR‐146a [2.55 (1.00–4.80) versus 6.46 (1.50–11.44) a.u.] were significantly lower (∼60, 40 and 60%, respectively) in the short compared with the normal sleep group. However, there were no significant group differences in circulating levels of miR‐34a, miR‐92a, miR‐145 and miR‐150. In summary, chronic short sleep is associated with a marked reduction in circulating levels of miR‐125a, miR‐126 and miR‐146a. Dysregulation of these miRNAs might contribute to the increased inflammatory burden and endothelial dysfunction associated with habitual insufficient sleep.