scholarly journals The miRNA Expression Profile in Acute Myocardial Infarct Using Sheep Model with Left Ventricular Assist Device Unloading

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaoqian Yan ◽  
Yu Gan ◽  
Haibo Chen ◽  
Guangmao Liu ◽  
Shengshou Hu ◽  
...  

This study attempted to establish miRNA expression profiles in acute myocardial infarct (AMI) sheep model with left ventricular assist device (LVAD) unloading. AMI was established in sheep model and FW-II type axial flow pump was implanted to maintain continuous unloading for 3 days. The cardiomyocyte survival, inflammatory cell infiltration, and myocardial fibrosis were detected by tissue staining, and cardiomyocyte apoptosis was detected by TUNEL assay. High throughput sequencing technique was used to detect miRNA expression in cardiomyocytes and to establish miRNA expression profile. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were established. miRNA sequencing results identified 152 known mature miRNAs and 1582 new mature miRNAs. The unloading and control groups differentially expressed genes, of which RT-PCR verified oar-miR-19b and oar-miR-26a. The GO and KEGG pathway annotation and enrichment established that the regulating functions and signaling pathways of these miRNAs were closely related to cardiovascular diseases (CVD). In this study, LVAD effectively reduced the cell death degree of cardiomyocyte in MI. The established miRNA expression profiles of AMI and LVAD intervention in this study suggest that the expression profile could be used to explore the unknown miRNA and the regulatory mechanisms involved in AMI.

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1034
Author(s):  
Dawid Szczepankiewicz ◽  
Wojciech Langwiński ◽  
Paweł Kołodziejski ◽  
Ewa Pruszyńska-Oszmałek ◽  
Maciej Sassek ◽  
...  

Adipose tissue is a major source of circulating exosomal microRNAs (miRNAs) that are modulators of the immune response in various types of tissues and organs, including airways. Still, no evidence exists if allergic airway inflammation may affect fat tissue inflammation via alterations in the miRNA expression profile. Therefore, we investigated the miRNA expression profile in the adipose tissue upon induced allergic inflammation in the airways in the rat. Brown Norway rats were chronically sensitized to house dust mite extract for seven weeks. Body composition was performed using MiniSpec Plus. The eosinophil count and the total IgE level were determined to confirm the induction of allergic inflammation. MiRNA expression profiling was done using the next-generation sequencing with validation by qPCR. We found that allergic airway inflammation significantly increased fat in adipose tissue, glucose concentration, and the gene expression of adipose tissue-derived proinflammatory peptides (leptin, TNFα). In miRNA-seq analysis, we showed significant differences in the expression of 36 mature miRNAs, three precursors, and two miRNA families in adipose tissue of allergic rats. Two miRNAs—miRNA-151-5p and miRNA-423-3p—showed significantly increased expression in qPCR in adipose tissue and lungs of sensitized animals. Allergic airway inflammation affects fat tissue and alters miRNA expression profile in adipose tissue in the rat.


2019 ◽  
Author(s):  
Xinmiao Jia ◽  
Xiaoke Liu ◽  
Zhongshuai Wang ◽  
Heyi Zheng ◽  
Jun Li

Abstract Background Syphilis is a chronic sexually transmitted disease caused by infection with Treponema pallidum, which can invade various system organs, leading to clinical manifestations such as neurosyphilis, ocular syphilis, and cardiovascular syphilis and seriously endangering human health. Serofast status is a common outcome after syphilis treatment that presents an important clinical problem. At present, the etiology of serofast status remains unknown. Methods A systematic investigation of the microRNA (miRNA) expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with serofast status or secondary syphilis and of healthy control subjects was conducted using small RNA-seq. The expression of miRNAs was further confirmed by real-time fluorescence quantitative PCR (qPCR) assays. Results The data reveal a specific miRNA expression profile that was displayed in cells from patients with serofast status. Known and novel predicted (np)-miRNAs were also identified and verified, such as miR-338-5p, np-miR-163, np-miR-128, np-miR-244, and np-miR-5, which together may be used as indicators for treatment evaluation. The functions of genes targeted by the miRNAs differentially expressed in serofast status patients were further analyzed; these genes were found to be involved in various biological functions, such as T-cell receptor signaling pathways, metabolism, and growth. Our study presents the first systematic landscape of miRNAs in PBMCs from patients with serofast status and proposes specific miRNAs linked with serofast status that merit further investigation as potential biomarkers. Conclusion Our results provide further evidence that serofast status is closely related to host immune function. Additionally, the miRNA expression profile in PBMCs of patients with serofast status generated by this work offers insight into the complex immune network in humans. We hope our results can inspire the development of new treatment options for patients with serofast status.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yan Feng ◽  
Hui Zhao ◽  
Fu-Dong Shi ◽  
Weina Jin

Objectives: To screen miRNA profile of peripheral NK cells in ischemic stroke mouse model and investigate a most promising candidate (miR-1224) for post-transcriptional regulation of NK cell function after ischemic stroke. Methods: Mice were subjected to a 60 min focal cerebral ischemia produced by transient intraluminal occlusion of MCAO. For NK cell isolation, cell suspensions from the spleens after reperfusion were enriched for NK cells using magnetic-bead sorting system after staining with anti-NK1.1 microbeads. The nCounter Mouse miRNA array was used to analyze miRNA expression profile in splenic NK cells over the time course of experimental ischemic stroke. Based on the miRNA data, we further in vitro modulated miR-1224 in NK cells using mimics or inhibitor, then injected i.v into Rag2-/-γc-/- recipient mice. Neurological function score was compared and spontaneous infection was assessed by pulmonary bacteria colony culture, and changes in potential signaling pathway (SP1/TNF-α) were verified by rt-PCR and western blot. Results: Through miRNA expression profile analysis, we have identified significant changes at each time point in peripheral NK cells after cerebral ischemia. Among all screened miRNA, miR-1224 remarkably increased in MCAO group, which was verified by PCR. Then isolated NK cells treated with mimics or inhibitors, were transferred to Rag2-/-γc-/- recipient mice. Compared with WT mice, Rag2-/-γc-/- mice with miR-1224 inhibitor exhibited increased NK cell number, enhanced NK cell activation/cytotoxicity feature, as well as better neurological behaviors and reduced pulmonary infection after MCAO. Moreover, compared with the control group, NK cells with miR-1224 inhibitor showed significantly increased SP1 gene and protein phosphorylation. As SP1 gene is one of the potential targets of miR-1224, this study suggests that miR-1224 may regulate NK cell function after MCAO, which is associated with SP1 pathway. Conclusion: The miRNA profiling of splenic NK cells provided insight into the functional mechanism and signaling pathways underlying the distinct organ-specific NK cell properties, which will contribute to the better understanding of NK cell mediated immune-response in relation to different stages of stroke.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Genya Sunagawa ◽  
Keita Saku ◽  
Takuya Nishikawa ◽  
Nobuhiro Suematsu ◽  
Toru Kubota ◽  
...  

Introduction: Extracorporeal membrane oxygenation (ECMO) supports hemodynamics in cardiogenic shock (CS) at the expense of left ventricular (LV) overload. LV assist device (LVAD) also supports hemodynamics, whereas LVAD unloads LV. Therefore, the combination of ECMO and LVAD would augment hemodynamic support and unload LV. We hypothesized that the combination therapy in acute myocardial infarct (AMI) in CS could synergistically improve hemodynamics and unload LV, which, in turn, reduces infarct size. Methods: In protocol 1, we ligated coronary arteries and created AMI with CS in 5 mongrel dogs (15.1±0.3 kg). We transvascularly introduced Impella CP into LV. We kept the ECMO flow constant at 1.8L/min. We compared hemodynamics and the LV pressure-volume area (PVA, an index of LV oxygen consumption) under 3 conditions; Control, ECMO, and ECMO+Impella (ECPELLA) in each dog. In protocol 2 (n=15), we ligated coronary arteries for 180 min and then reperfused. We activated Impella CP and/or ECMO from 60 min after the coronary ligation to the end of the experiment. We allocated dogs into 3 groups, no support (Control), ECMO, and ECPELLA and compared infarct size at 180 min after reperfusion among 3 groups. Results: In protocol 1, both ECMO and ECPELLA increased arterial pressure compared to Control (Control: 63±9, ECMO: 88±10 and ECPELLA: 97±18 mmHg, p < 0.05), and resolved the CS status. ECPELLA strikingly reduced PVA by 83% relative to Control (1500±326, 2038±357 and 258±182 mmHg*ml, p<0.001). In protocol 2, ECPELLA markedly reduced the infarct size (15±8%) compared to Control (53±7%, p<0.05) and ECMO (39±10%, p<0.05). Conclusions: ECPELLA before reperfusion markedly improved hemodynamics, reduced PVA, and limited infarct size in a dog model of MI with CS. ECPELLA could prevent ECMO-induced LV overload and synergistically exert powerful anti-infarct effects in AMI with CS.


2017 ◽  
Vol 24 (10) ◽  
pp. 543-553 ◽  
Author(s):  
Maria Denaro ◽  
Clara Ugolini ◽  
Anello Marcello Poma ◽  
Nicla Borrelli ◽  
Gabriele Materazzi ◽  
...  

Noninvasive encapsulated follicular variants of papillary thyroid carcinomas have been recently reclassified as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs). NIFTPs exhibit a behavior that is very close to that of follicular adenomas but different from the infiltrative and invasive follicular variants of papillary thyroid carcinomas (FVPTCs). The importance of miRNAs to carcinogenesis has been reported in recent years. miRNAs seem to be promising diagnostic and prognostic molecular markers for thyroid cancer, and the combination of miRNA expression and mutational status might improve cytological diagnosis. The aim of the present study was to evaluate the miRNA expression profile in wild-type, RAS- or BRAF-mutated NIFTPs, infiltrative and invasive FVPTCs, and follicular adenomas using the nCounter miRNA Expression assay (NanoString Technologies). To identify the significant Kyoto Encyclopedia of Genes and Genomes (KEGG) molecular pathways associated with deregulated miRNAs, we used the union of pathways option in DNA Intelligent Analysis (DIANA) miRPath software. We have shown that the miRNA expression profiles of wild-type and mutated NIFTPs could be different. The expression profile of wild-type NIFTPs seems comparable to that of follicular adenomas, whereas mutated NIFTPs have an expression profile similar to that of infiltrative and invasive FVPTCs. The upregulation of 4 miRNAs (miR-221-5p, miR-221-3p, miR-222-3p, miR-146b-5p) and the downregulation of 8 miRNAs (miR-181a-3p, miR-28-5p, miR-363-3p, miR-342-3p, miR-1285-5p, miR-152-3p, miR-25-3p, miR-30e-3) in mutated NIFTPs compared to wild-type ones suggest a potential invasive-like phenotype by deregulating the specific pathways involved in cell adhesion and cell migration (Hippo signaling pathway, ECM-receptor interaction, adherens junction, regulation of actin cytoskeleton, fatty acid biosynthesis and metabolism).


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Katia de Paiva Lopes ◽  
Tatiana Vinasco-Sandoval ◽  
Ricardo Assunção Vialle ◽  
Fernando Mendes Paschoal ◽  
Vanessa Albuquerque P. Aviz Bastos ◽  
...  

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