MicroRNA 21 Inhibits Left Ventricular Remodeling in the Early Phase of Rat Model with Ischemia-reperfusion Injury by Suppressing Cell Apoptosis

Qin, Yanjun; Yu, Yueqing; Hua, Dong; Bian, Xing; Guo, Xuan; Dong, Shaohong

doi:10.7150/ijms.4514

Cited by 82 publications

(62 citation statements)

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“…Elevated miR-21 expression may induce cardiac hypertrophy and fibrosis by increasing the secretion of fibroblast growth factor-2, thereby inhibiting the apoptosis of cardiac fibroblasts [33]. miR-21 upregulation during the early phase of ischemia-reperfusion injury has been shown to attenuate cardiomyocyte apoptosis [34]. Moreover, miR-21 has been reported to attenuate the death of ischemic cortical neurons by reducing the expression of the FasL (Fas ligand) gene [35].…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNA-146a and MicroRNA-21 Predict Left Ventricular Remodeling after ST-Elevation Myocardial Infarction

et al. 2015

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Objectives: MicroRNA (miR)-146a and miR-21 have been reported to participate in inflammatory reactions and fibrosis. Excessive inflammation and cardiac fibrosis may play important roles in the development of left ventricular remodeling (LVR). This study assessed whether miR-146a, miR-21 and other biomarkers could predict LVR after myocardial infarction (MI). Methods: Circulating miR-146a, miR-21 and other biomarker levels were measured in 198 patients with acute MI 5 days after primary percutaneous coronary intervention (PCI). All patients were assessed by transthoracic echocardiography on day 5 and 1 year after primary PCI. Results: Concentrations of circulating miR-146a, miR-21, C-reactive protein, creatine kinase MB type and troponin I, as well as estimated glomerular filtration rate (eGFR) and left ventricular ejection fraction (LVEF), were significantly higher in patients with than in those without LVR (p < 0.05). Multivariate logistic regression analysis showed that circulating miR-146a (odds ratio, OR = 2.127, p < 0.0001), miR-21 (OR = 1.119, p < 0.0001), eGFR (OR = 0.939, p = 0.0137) and LVEF (OR = 0.802, p = 0.0048) were independent predictors of LVR development. The area under the curve for the combination of miR-146a and miR-21 was significantly higher than for either alone. Conclusion: Circulating miR-146a and miR-21 may be novel biomarkers predictive of LVR after acute MI. Their combination may better predict LVR than either alone.

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Section: Discussionmentioning

confidence: 99%

Circulating MicroRNA-146a and MicroRNA-21 Predict Left Ventricular Remodeling after ST-Elevation Myocardial Infarction

et al. 2015

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“…Hemodynamic examination: Hemodynamic examination was performed as previously described. 8) Hemodynamic parameters, including the heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximal rate of rise in blood pressure in the ventricular chamber (+dp/dt max), and maximal rate of decline in blood pressure in the ventricular chamber (-dp/dt max) were measured and recorded by an 8-channel polygraph system (RM-6000). RNA extraction and qRT-PCR analysis: Total RNA was obtained separately from the infarcted, border, and non-infarcted areas of the LV at 24 hours after LAD ligation, as well as from the sham group at the same time.…”

Section: Measurement Of the Dimensions Of The Left Ventricles (Lv) Andmentioning

confidence: 99%

“…6) Our previous studies have shown that miR-21 plays an important role in the protection of heart function and is a possible mechanism in ischemic disease. 7,8) By analyzing conserved miRNAs that were upregulated in a rat AMI model, we identified miR-214 as a sensitive marker of ischemic injury. 7) In the current study, we designed a rat AMI model with the aim of investigating whether miR-214 had a protective effect on heart function.…”

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confidence: 99%

MicroRNA-214 Inhibits Left Ventricular Remodeling in an Acute Myocardial Infarction Rat Model by Suppressing Cellular Apoptosis via the Phosphatase and Tensin Homolog (PTEN)

et al. 2016

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SummaryThe aims of the present study were to determine the role of miR-214 on left ventricular remodeling of rat heart with acute myocardial infarction (AMI) and to further investigate the underlying mechanism of miR-214-mediated myocardial protection. AMI was induced in which adenovirus-expressing miR-214 (Ad-miR-214), anti-miR-214, or Ad-GFP had been delivered into rats hearts 4 days prior, while a phosphatase and tensin homolog (PTEN) inhibitor was administered via intra-peritoneal injection 30 minutes prior to AMI. Changes in hemodynamic parameters were detected and recorded. Left ventricular (LV) dimensions and LV/BW were measured. Quantitative RT-PCR was used to determine the miR-214 expression levels of the myocytes in the infarcted, border, and non-infarcted areas of the LV. Myocardial infarct size was also measured. Flow cytometry analysis was performed to examine cellular apoptosis. Western blot analysis was performed to examine PTEN expression. The results showed that miR-214 was upregulated in both border and infarcted areas. Myocardial cell apoptosis was decreased in the Ad-miR-214 group, but was increased in the anti-miR-214 group, while there were no differences among the Ad-GFP-group, PTEN-ad-miR-214 group, or PTEN-anti-miR-214 group. Myocardial infarct size, LV dimensions, heart rate (HR), and LV end-diastolic pressure (LVEDP) were decreased while the maximal rates of rise or decline in blood pressure in the ventricular chamber (± dp/dt) and LV systolic pressure (LVSP) were increased in the Ad-miR-214 group, all of which exhibited opposite changes in the anti-miR-214 group. PTEN was downregulated in the Ad-miR-214 group and upregulated in the anti-miR-214 group. PTEN was decreased in both the border and infarcted areas compared with non-infarcted areas. The study results suggest that Ad-miR-214 improves LV remodeling and decreases the apoptosis of myocardial cells through PTEN, suggesting a possible mechanism by which Ad-miR-214 functions in protecting against AMI injury. (Int Heart J 2016; 57: 247-250) Key words: Adenovirus expressing transfer, QRT-PCR analysis, Western blot analysis, Rat acute myocardial model C ardiovascular diseases constitute the major leading cause of death globally, and current estimates indicate that as many as 1 in 6 deaths per year can be attributed to coronary disease and associated myocardial ischemia in the United States.1) Cardiac remodeling after acute myocardial infraction (AMI) results in poor cardiac performance, which often leads to heart failure.2) Myocardial fibrosis results in mechanical stiffness, which contributes to ventricular contractile dysfunction. 3)MicroRNAs (miRNAs, miRs) are a class of endogenous, small (~22 nt) non-coding single-stranded RNAs, which have highly conserved sequences among species.4) Approximately 1,400 miRNAs have been identified thus far in humans, and this number is growing.5) An individual miRNA is as important as a transcription factor due to its ability to regulate the expression of multiple target genes.5) The majority of ce...

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“…Furthermore, subsequent reoxygenation may further aggravate the damage (6). Multiple miRNAs have been shown to function as protectors against hypoxia/reoxygenation (H/R)-induced myocardial injury (7)(8)(9). However, the specific molecular mechanisms underlying this effect have remained elusive.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of microRNA-101 attenuates hypoxia/reoxygenation-induced apoptosis through induction of autophagy in H9c2 cardiomyocytes

Jiang

Chen

et al. 2015

Molecular Medicine Reports

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Abstract. Autophagy is a cellular self-catabolic process responsible for the degradation of proteins and organelles. Autophagy is able to promote cell survival in response to stress, and increased autophagy amongst cardiomyocytes has been identified in conditions of heart failure, starvation and ischemia/reperfusion. However, the detailed regulatory mechanisms underlying autophagy in heart disease have remained elusive. MicroRNAs (miRNAs) have been implicated in the regulation of autophagy in cells under stress. In the present study, the protective effect of miRNA (miR)-101 on hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis was investigated. It was revealed that H/R induced apoptosis in H9c2 cardiomyocytes, accompanied by a downregulation of miR-101 expression. Further investigation identified Ras-related protein Rab-5A (RAB5A) as a direct target of miR-101. RAB5A was previously reported to be involved in autophagy; therefore, the present study further focused on the role of miR-101 in the regulation of autophagy under H/R and found that the inhibition of miR-101 attenuated H/R-induced apoptosis, at least partially, via the induction of autophagy. In conclusion, the results of the present study revealed a beneficial effect of miR-101 inhibition on H/R-induced apoptosis in cardiomyocytes, indicating that miR-101 inhibition may present a potential therapeutic agent in the treatment or prevention of heart diseases. IntroductionAutophagy is a cellular self-catabolic process responsible for the degradation of long-lived proteins and organelles. During autophagy, cytoplasmic constituents are sequestered into autophagosomes and degraded via the lysosomal pathway (1).Autophagy is able to promote cell survival in response to stress. However, progressive autophagy also induces cell death (2). Therefore, autophagy not only has a crucial role in the regulation of normal development, but dysregulated or defective autophagy is associated with disease.MicroRNAs (miRNAs) are a group of endogenous, non-coding, single-strand, small RNAs of 22-25 nucleotides, which regulate gene expression at the post-transcriptional level, predominantly through base pairing with the 3'-untranslated region (3'-UTR) of target mRNAs, which results in mRNA degradation or translational repression (3). It has been revealed that miRNAs regulate >30% of genes, which are associated with almost all major cellular processes, including cell proliferation, differentiation, apoptosis and migration, as well as immune responses (4). Myocardial tissue injury induced by ischemia and hypoxia is a major factor underlying the development of fatal diseases. The main cause of myocardial ischemic injury is myocardial cell apoptosis induced by myocardial hypoxia (5). Furthermore, subsequent reoxygenation may further aggravate the damage (6). Multiple miRNAs have been shown to function as protectors against hypoxia/reoxygenation (H/R)-induced myocardial injury (7-9). However, the specific molecular mechanisms underlying this effect have remained elusive.Accumu...

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MicroRNA 21 Inhibits Left Ventricular Remodeling in the Early Phase of Rat Model with Ischemia-reperfusion Injury by Suppressing Cell Apoptosis

Cited by 82 publications

References 37 publications

Circulating MicroRNA-146a and MicroRNA-21 Predict Left Ventricular Remodeling after ST-Elevation Myocardial Infarction

Circulating MicroRNA-146a and MicroRNA-21 Predict Left Ventricular Remodeling after ST-Elevation Myocardial Infarction

MicroRNA-214 Inhibits Left Ventricular Remodeling in an Acute Myocardial Infarction Rat Model by Suppressing Cellular Apoptosis via the Phosphatase and Tensin Homolog (PTEN)

Inhibition of microRNA-101 attenuates hypoxia/reoxygenation-induced apoptosis through induction of autophagy in H9c2 cardiomyocytes

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