Mechanism of programmed cell death factor 4/nuclear factor-κB signaling pathway in porcine coronary micro-embolization-induced cardiac dysfunction

Su, Qiang; Li, Lang; Wang, Jiangyou; Zhou, You; Liu, Yangchun

doi:10.1177/1535370215573400

Cited by 10 publications

(7 citation statements)

References 18 publications

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“…The probe frequency was 12 MHz. All values were the average measurements of three cardiac cycles 31 . Echocardiographic data were recorded and analyzed by blinding to different treatments.…”

Section: Methodsmentioning

confidence: 99%

The mechanism of miR-142-3p in coronary microembolization-induced myocardiac injury via regulating target gene IRAK-1

et al. 2019

Cell Death Dis

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Coronary microembolization (CME) is a common complication seen during primary percutaneous coronary intervention (pPCI). CME-induced myocardiac inflammation is the primary cause of myocardiac injury. Dysregulated miR-142-3p has been implicated in multiple cardiovascular diseases and is significantly downregulated in CME-induced myocardial injury. However, the role of miR-142-3p in CME-induced myocardial injury is unclear. This study herein built a porcine CME model by infusing microembolization spheres into the left anterior descending branch via a microcatheter, and detected the downregulation of miR-142-3p in the myocardial tissues of CME pigs. Echocardiography, hematoxylin basic fuchsin picric acid (HBFP) staining, and western blotting of NF-κB p65, TNF-α, IL-1β, and IL-6 showed that the pharmacological overexpression of miR-142-3p using agomiR has improved cardiac function and attenuated CME-induced myocardiac inflammatory response, while its inhibition using antagomiR demonstrated inverse effects. Moreover, in vitro experiments demonstrated IRAK-1 as a direct target gene of miR-142-3p. Luciferase reporter assays, quantitative real-time polymerase chain reaction and western blotting demonstrated its effects in controlling the inflammation of cardiomyocytes. It is noteworthy that miR-142-3p was found to be decreased in the plasma of STEMI patients undergoing pPCI with no-reflow, indicating a potential clinical relevance of miR-142-3p. The receiver–operator characteristic curve indicated that plasma miR-142-3p might be an independent predictor of no-reflow during pPCI in patients with STEMI. Therefore, overexpression of miR-142-3p acts as a novel therapy for CME-induced myocardial injury.

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Section: Methodsmentioning

confidence: 99%

The mechanism of miR-142-3p in coronary microembolization-induced myocardiac injury via regulating target gene IRAK-1

et al. 2019

Cell Death Dis

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“…NF-κB activation serves a critical role in coronary microembolism-induced cardiac dysfunction and advanced heart failure ( 18 ). For example, NF-κB activation and the subsequent inflammatory response contribute to cardiac dysfunction and maladaptive left ventricular remodeling following MI ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of potentially relevant genes for myocardial infarction using RNA sequencing data analysis

Zhao

et al. 2017

Exp Ther Med

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Myocardial infarction (MI) is a heart disease with high morbidity and mortality rates, thus it is critical to identify genes that serve roles during its pathogenesis. The objective of the present study was to identify potentially relevant genes during the progression of the disease. Blood samples from patients with MI and normal controls (n=3/group) were obtained, the RNA was extracted and cDNA libraries were established. RNA sequencing (RNA-seq) was performed on a HiSeq 2500 platform and fragments per kilobase of exon per million fragments mapped was utilized to calculate the gene expression value following preprocessing of the RNA-seq data. Electronic validation of several identified differentially expressed genes (DEGs) was performed on a Gene Expression Omnibus (GEO) dataset GSE59867 (390 cases and 46 healthy controls). Functional enrichment and protein-protein interaction network analysis was conducted for DEGs. A total of 977 DEGs, including 817 upregulated and 160 downregulated genes were identified in patients with MI. These DEGs were significantly enriched for ‘positive regulation of the immune system process,’ ‘inflammatory response,’ ‘regulation of I-kappaB-kinase/NF-kappaB signaling’ and ‘TNF signaling pathway’. A protein-protein interaction network of the top 40 DEGs was used to identify high degree genes, including interferon induced protein with tetratricopeptide repeats 3 (IFIT3), MX dynamin like GTPase 1 (MX1), major histocompatibility complex, class II, DQ α1 (HLA-DQA1), RAR related orphan receptor A (RORA), prostaglandin D2 synthase (PTGDS), cysteine rich protein 2 (CRIP2), collagen type VI α 2 chain (COL6A2) and S100 calcium binding protein P (S100P). The results of validation in the GEO dataset were consistent with the sequencing analysis. A total of eight genes, including IFIT3, MX1, HLA-DQA1, RORA, PTGDS, CRIP2, COL6A2 and S100P may therefore be considered as potentially relevant genes in the pathology of MI.

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“…10 We previously found that CME-induced activation of PDCD4/NF-κB/TNF-α pathway had an important role in CME-induced myocardial inflammatory responses. 5 Overexpression of microRNA-21 in cardiomyocytes regulates its target genes to exert anti-inflammatory and antiapoptotic effects resulting in myocardial protection. Animal experiments confirmed that ischemic preconditioning significantly upregulated microRNA-21 expression and downregulated its target gene PDCD4 to prevent the PDCD4-mediated activation of activated protein-1 and myocardial apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…The inhibition of PDCD4/NF-κB/TNF-α pathway reduced CME-induced myocardial damage and improved cardiac function. 5 It has been recently reported that microRNA-21 exerts a protective effect on myocardium mainly through the regulation of PDCD4-mediated antiapoptotic and anti-inflammatory pathways. 6 Therefore, we speculated that transfection of microRNA-21 into myocardium to regulate PDCD4 expression could potentially inhibit CME-induced activation of PDCD4/NF-κB/ TNF-α pathway and protect the myocardium.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

et al. 2015

Gene Ther

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The programmed cell death 4/nuclear factor-κB/tumor necrosis factor α (PDCD4/NF-κB/TNF-α) signaling pathway has an important role in coronary microembolization (CME)-induced inflammation. microRNA-21 protects myocardium mainly via regulation of its target gene PDCD4. Therefore, in this study we investigated the effect of ultrasound-guided microbubble-mediated microRNA-21 transfection on cardiac function in CME pig model and determined the potential mechanisms involved. The pig CME model was established by microcatheter-mediated injection of microembolization beads into the left anterior descending artery. The CME with microRNA transfection group was injected with plasmid-microbubble mixture through the marginal ear vein 4 days before CME treatment, along with ultrasound to the myocardium. Cardiac function indices were examined by cardiac ultrasound; infarct area was measured by hematoxylin-eosin and hematoxylin-basic Fuchsin-picric acid staining of tissue pathological sections; green fluorescent protein-labeled gene expression levels were evaluated by fluorescent microscopy in frozen sections; myocardial PDCD4 and TNF-α mRNA levels were measured by fluorescent quantitative PCR and protein levels were measured by western blotting; and NF-κB activity was tested by electrophoretic mobility shift assay. Compared with the CME group, the CME with ultrasound-mediated microRNA transfection group demonstrated improved CME-induced cardiac dysfunction (P<0.05). Compared with the CME group, the CME with ultrasound-mediated microRNA transfection group showed significantly lower PDCD4 expression and NF-κB activity (P<0.05). Ultrasound microbubble-mediated microRNA-21 transfection effectively improved CME-induced cardiac dysfunction via inhibition of PDCD4/NF-κB/TNF-α signal transduction pathway.

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Mechanism of programmed cell death factor 4/nuclear factor-κB signaling pathway in porcine coronary micro-embolization-induced cardiac dysfunction

Cited by 10 publications

References 18 publications

The mechanism of miR-142-3p in coronary microembolization-induced myocardiac injury via regulating target gene IRAK-1

The mechanism of miR-142-3p in coronary microembolization-induced myocardiac injury via regulating target gene IRAK-1

Identification of potentially relevant genes for myocardial infarction using RNA sequencing data analysis

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

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