Ultrasound-targeted microbubble destruction-mediated microRNA-21 transfection regulated PDCD4/NF-κB/TNF-α pathway to prevent coronary microembolization-induced cardiac dysfunction

Su, Qiang; Li, L; Liu, Y; Zhou, Yi; Wang, J; Wen, Wang

doi:10.1038/gt.2015.59

Cited by 30 publications

(22 citation statements)

References 23 publications

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“…This result was consistent with Liang's report, which showed that downregulated PDCD4 suppressed the expression of proinflammatory factors and promoted the production the anti-inflammatory factor, IL-10 [24]. Other studies suggest that the PDCD4/nuclear factor- κ B/tumor necrosis factor α (PDCD4/NF- κ B/TNF- α ) signaling pathway plays an important role in coronary microembolization- (CME-) induced inflammation, and inhibition of PDCD4 could improve CME-induced cardiac dysfunction [41]. Moreover, PDCD4 improved the inflammatory response via nuclear factor- κ B (NF- κ B), activating and inhibiting the production of IL-10 [24].…”

Section: Discussionmentioning

confidence: 99%

miR-155 Regulated Inflammation Response by the SOCS1-STAT3-PDCD4 Axis in Atherogenesis

Guo

Shi

et al. 2016

Mediators of Inflammation

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Inflammation response plays a critical role in all phases of atherosclerosis (AS). Increased evidence has demonstrated that miR-155 mediates inflammatory mediators in macrophages to promote plaque formation and rupture. However, the precise mechanism of miR-155 remains unclear in AS. Here, we also found that miR-155 and PDCD4 were elevated in the aortic tissue of atherosclerotic mice and ox-LDL treated RAW264.7 cells. Further studies showed that miR-155 not only directly inhibited SOCS1 expression, but also increased the expression of p-STAT and PDCD4, as well as the production of proinflammation mediators IL-6 and TNF-α. Downregulation of miR-155 and PDCD4 and upregulation of SOCS1 obviously decreased the IL-6 and TNF-α expression. In addition, inhibition of miR-155 levels in atherosclerotic mice could notably reduce the IL-6 and TNF-α level in plasma and aortic tissue, accompanied with increased p-STAT3 and PDCD4 and decreased SOCS1. Thus, miR-155 might mediate the inflammation in AS via the SOCS1-STAT3-PDCD4 axis. These results provide a rationale for intervention of intracellular miR-155 as possible antiatherosclerotic targets.

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Section: Discussionmentioning

confidence: 99%

miR-155 Regulated Inflammation Response by the SOCS1-STAT3-PDCD4 Axis in Atherogenesis

Guo

Shi

et al. 2016

Mediators of Inflammation

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“…CME may also result in myocardial contractile dysfunction and notable arrhythmias which are strongly associated with cardiac dysfunction and deterioration of clinical follow-ups [5-7]. Recently, research has found that microRNAs (miRs) and myocardial autophagy may play a vital role in CME [8, 9]; however, the specific molecular mechanism of these factors remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Potential Involvement of MiR-30e-3p in Myocardial Injury Induced by Coronary Microembolization via Autophagy Activation

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Coronary microembolization (CME) can lead to no-reflow or slow reflow, which is one of the important reasons for loss of clinical benefit from myocardial reperfusion therapy. MicroRNAs and autophagy are heavily implicated in the occurrence and development of almost all cardiovascular diseases. Therefore, the present study was designed to investigate the role of miR-30e-3p and autophagy in CME-induced myocardial injury rat model. Methods: Sixty rats were randomly divided into six groups: sham, CME 1h,3h,6h,9h, and 12h (n = 10 per group). Our CME rat model was created by injecting polyethylene microspheres (42mm) into the left ventricle of the heart; the sham group was injected with same volume of normal saline. The cardiac function and serum cardiac troponin I (cTnI) level of each group was measured. HE staining and HBFP staining were used to evaluate the myocardial micro-infarction area of myocardium tissue samples. Then RT-qPCR and western blot were used to detect the expression of miR-30e-3p and, autophagy related protein LC3-II and p62, respectively. Transmission electron microscope (TEM) was used to identify autophagic vacuoles in tissue samples. Results: The cardiac function of the CME 6h,9h, and 12h groups were significantly decreased compared to the sham group (P < 0.05) and the cTnI level in each group were also significantly increased (P < 0.05). The expression of miR-30e-3p in the CME 6h, 9h and 12h group were decreased significantly compared with the sham group (P < 0.05). Meanwhile, the expression of autophagy related protein LC3-II decreased significantly and p62 increased significantly in the CME 9h and 12h group (P < 0.05). TEM images showed typical autophagic vacuoles for each of the CME groups. Conclusions: Myocardial miR-30e-3p is down regulated after CME and is accompanied by inhibited autophagy and decreased cardiac function. Therefore, miR-30e-3p may be involved in CME-induced cardiac dysfunction by regulating myocardial autophagy.

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“…Among the differentially expressed miRNAs, miR-21 showed the most significant increase in expression, and it played a protective role in hypoxia/ reoxygenation-induced apoptosis by regulating the expression of programmed cell death factor 4 [14]. Our previous study also found that overexpression of miR-21 inhibited CME-induced myocardial inflammatory response and improved heart function via inhibition of the PDCD4/NF-κB/TNF-α signaling pathway [15]. Still, the expression and mechanism of action of other miRNAs involved in CME-induced myocardial injury need to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

MiRNA Expression Profile of the Myocardial Tissue of Pigs with Coronary Microembolization

Zhao

et al. 2017

Cell Physiol Biochem

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Background/Aims: Coronary microembolization (CME) is a serious complication of coronary heart disease and is considered as a strong predictor of poor long-term prognosis and major cardiac adverse events. Here, we identified differentially expressed microRNAs (miRNAs) in the myocardial tissue of CME pigs, and predicted and analyzed the possible functions of their target genes. Methods: Twelve Bama mini-pigs were randomly assigned to the sham and CME group (n = 6 in each group). The two groups were compared with regard to heart function, area of infarction, cardiomyocyte apoptosis, and myocardial expression of TNF-α, IL-1β and IL-6. Further, miRNA chip analysis was used to screen for differentially expressed miRNAs, and the results were validated by real-time PCR. Bioinformatics methods were used to predict and analyze the functions of the target genes of the identified miRNAs. Results: The model CME pigs showed significantly increased expression of TNF-α, IL-1β and IL-6, as well as micro-infarction lesions and cell apoptosis in the myocardial tissue. Thus, the model was established successfully. In the myocardial tissue of the CME pigs, the expression of ssc-miR-92b-5p, ssc-miR-491, ssc-miR-874, ssc-miR-425-3p, ssc-miR-376a-5p, ssc-miR-370, ssc-miR-30c-3p, ssc-miR-493-5p and ssc-miR-323 was significantly increased, whereas the expression of ssc-miR-136 and ssc-miR-142-3p was significantly decreased. GO and KEGG pathway analysis indicated that the target genes of these miRNAs are mainly associated with cell proliferation, apoptosis, necrosis, inflammation, and fibrosis. Conclusion: The differentially expressed miRNAs identified in the myocardial tissue of CME pigs could be new biomarkers or potential treatment targets for CME.

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Ultrasound-targeted microbubble destruction-mediated microRNA-21 transfection regulated PDCD4/NF-κB/TNF-α pathway to prevent coronary microembolization-induced cardiac dysfunction

Cited by 30 publications

References 23 publications

miR-155 Regulated Inflammation Response by the SOCS1-STAT3-PDCD4 Axis in Atherogenesis

miR-155 Regulated Inflammation Response by the SOCS1-STAT3-PDCD4 Axis in Atherogenesis

Potential Involvement of MiR-30e-3p in Myocardial Injury Induced by Coronary Microembolization via Autophagy Activation

MiRNA Expression Profile of the Myocardial Tissue of Pigs with Coronary Microembolization

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