scholarly journals Expression Profile of Circulating MicroRNAs in Dogs With Cardiac Hypertrophy: A Pilot Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Woong-Bin Ro ◽  
Min-Hee Kang ◽  
Doo-Won Song ◽  
Sung-Hun Lee ◽  
Hee-Myung Park
Keyword(s):  
Pilot Study ◽  
Cardiac Hypertrophy ◽  
Microarray Analysis ◽  
Expression Profile ◽  
Heart Diseases ◽  
Differentially Expressed ◽  
Serum Samples ◽  
Down Regulation ◽  
Circulating Micrornas ◽  
Healthy Dogs

This study aimed to identify the expression profile of circulating microRNAs in dogs with eccentric or concentric cardiac hypertrophy. A total of 291 microRNAs in serum samples of five dogs with myxomatous mitral valve degeneration (MMVD) and five dogs with pulmonic stenosis (PS) were compared with those of five healthy dogs using microarray analysis. Results of microarray analysis revealed up-regulation of cfa-miR-130b [fold change (FC) = 2.13, p = 0.014), down-regulation of cfa-miR-375 (FC = 1.51, p = 0.014), cfa-miR-425 (FC = 2.56, p = 0.045), cfa-miR-30d (FC = 3.02, p = 0.047), cfa-miR-151 (FC = 1.89, p = 0.023), cfa-miR-19b (FC = 3.01, p = 0.008), and cfa-let-7g (FC = 2.53, p = 0.015) in MMVD group which showed eccentric cardiac hypertrophy, up-regulation of cfa-miR-346 (FC = 2.74, p = 0.032), down-regulation of cfa-miR-505 (FC = 1.56, p = 0.016) in PS group which showed concentric cardiac hypertrophy, and down-regulation of cfa-miR-30c (FC = 3.45, p = 0.013 in MMVD group; FC = 3.31, p = 0.014 in PS group) and cfa-let-7b (FC = 11.42, p = 0.049 in MMVD group; FC = 5.88, p = 0.01 in PS group) in both MMVD and PS groups. In addition, the unsupervised hierarchical clustering of differentially expressed microRNAs in each group resulted in complete separation of healthy dogs from dogs with heart diseases. Therefore, eleven microRNAs among 291 microRNAs were identified as differentially expressed circulating microRNAs related to MMVD or PS in dogs. This pilot study demonstrates that the microRNAs identified in this study could be possible candidates for novel biomarker or therapeutic target related to cardiac hypertrophy in dogs.

scholarly journals Identification and Characterization of Circulating MicroRNAs as Novel Biomarkers in Dogs With Heart Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Woong-Bin Ro ◽  
Min-Hee Kang ◽  
Doo-Won Song ◽  
Heyong-Seok Kim ◽  
Ga-Won Lee ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Heart Diseases ◽  
Ductus Arteriosus ◽  
Canine Heart ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Circulating Micrornas ◽  
Concentric Hypertrophy ◽  
Novel Biomarkers ◽  
Healthy Dogs

Background: Previous studies in humans have confirmed dysregulations of circulating microRNAs (miRNAs) in patients with various cardiovascular diseases. However, studies on circulating miRNAs in dogs with various heart diseases are limited in number. This study aimed to identify significantly dysregulated circulating miRNAs and characterize them as novel biomarkers in dogs with heart diseases.Materials and Methods: Circulating levels of 11 miRNAs were investigated in serum samples of 82 dogs (72 with heart diseases and 10 healthy dogs) using quantitative reverse transcription-polymerase chain reaction. The results were correlated to clinical data including echocardiographic results and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels.Results: Upregulation of cfa-miR-130b was observed in dogs with myxomatous mitral valve degeneration (MMVD) stage B, patent ductus arteriosus, and pulmonic stenosis. In dogs with MMVD stage B, cfa-miR-130b was upregulated and correlated with clinical indices. In receiver operating characteristic (ROC) analysis, cfa-miR-130b accurately distinguished dogs with diseases from healthy dogs. We also observed that cfa-miR-375 and cfa-let-7b were upregulated in dogs with concentric cardiac hypertrophy. The cfa-miR-375 was correlated with concentric hypertrophy indices and was an accurate indicator of concentric hypertrophy in ROC analysis.Conclusions: The miRNAs identified in this study may be used as novel biomarkers and possible candidates for therapeutic targets in various canine heart diseases.

Microarray analysis of gene expression during early stages of mild and severe cardiac hypertrophy

2006 ◽  
Vol 27 (3) ◽  
pp. 309-317 ◽  
Author(s):  
Sudarsan Rajan ◽  
Sarah S. Williams ◽  
Ganapathy Jagatheesan ◽  
Rafeeq P. H. Ahmed ◽  
Geraldine Fuller-Bicer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Microarray Analysis ◽  
Ventricular Hypertrophy ◽  
Molecular Mechanisms ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Differentially Expressed ◽  
Transgenic Mouse Models ◽  
Ventricular Tissue ◽  
Gene Transcripts

Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. We previously developed two transgenic mouse models that carry FHC-associated mutations in α-tropomyosin (TM): FHC α-TM175 mice show patchy areas of mild ventricular disorganization and limited hypertrophy, whereas FHC α-TM180 mice exhibit severe hypertrophy and fibrosis and die within 6 mo. To obtain a better understanding of the molecular mechanisms associated with the early onset of cardiac hypertrophy, we conducted a detailed comparative analysis of gene expression in 2.5-mo-old control, FHC α-TM175, and α-TM180 ventricular tissue. Results show that 754 genes (from a total of 22,600) were differentially expressed between the nontransgenic (NTG) and the FHC hearts. There are 178 differentially regulated genes between NTG and the FHC α-TM175 hearts, 388 genes are differentially expressed between NTG and FHC α-TM180 hearts, and 266 genes are differentially expressed between FHC α-TM175 and FHC α-TM180 hearts. Genes that exhibit the largest increase in expression belong to the “secreted/extracellular matrix” category, and those with the most significant decrease in expression are associated with “metabolic enzymes.” Confirmation of the microarray analysis was conducted by quantitative real-time PCR on gene transcripts commonly associated with cardiac hypertrophy.

scholarly journals Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Karin Sanders ◽  
Anouk Veldhuizen ◽  
Hans S. Kooistra ◽  
Adri Slob ◽  
Elpetra P. M. Timmermans-Sprang ◽  
...  
Keyword(s):  
Decision Making ◽  
Cushing’S Syndrome ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Cushing's Syndrome ◽  
Differentially Expressed ◽  
Circulating Micrornas ◽  
Blood Samples ◽  
Non Invasive ◽  
Healthy Dogs

Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, non-invasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as diagnostic (presence of PDH or csACT) and/or prognostic (disease recurrence, histological grade) non-invasive biomarkers for canine Cushing's syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9x10−4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of <11. These results indicate that circulating miRNAs have the potential to be non-invasive biomarkers in dogs with Cushing's syndrome that may contribute to clinical decision making.

scholarly journals Circulating microRNAs as noninvasive biomarkers for canine Cushing's syndrome

2021 ◽  
Author(s):  
Karin Sanders ◽  
Anouk Veldhuizen ◽  
Hans S. Kooistra ◽  
Adri Slob ◽  
Elpetra P.M. Timmermans-Sprang ◽  
...  
Keyword(s):  
Decision Making ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Differentially Expressed ◽  
Circulating Mirnas ◽  
Circulating Micrornas ◽  
Blood Samples ◽  
Healthy Dogs ◽  
Noninvasive Biomarkers ◽  
One Year

Canine Cushing′s syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, noninvasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as noninvasive biomarkers for canine Cushing′s syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9x10-4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of < 11. These results indicate that circulating miRNAs have the potential to be noninvasive biomarkers in dogs with Cushing′s syndrome that may contribute to clinical decision-making.

Unraveling the Expression Profiles of Long Noncoding RNAs in Rat Cardiac Hypertrophy and Functions of lncRNA BC088254 in Cardiac Hypertrophy Induced by Transverse Aortic Constriction

Cardiology ◽  
2016 ◽  
Vol 134 (2) ◽  
pp. 84-98 ◽  
Author(s):  
Xiaoying Li ◽  
Lei Zhang ◽  
Jiangjiu Liang
Keyword(s):  
Cardiac Hypertrophy ◽  
Myocardial Hypertrophy ◽  
Heart Diseases ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Differentially Expressed ◽  
Transverse Aortic Constriction ◽  
Rt Pcr ◽  
Aortic Constriction

Long noncoding RNAs (lncRNAs), although initially considered as genomic transcription noise, have been demonstrated to play pivotal roles in multiple biological processes and are increasingly recognized as contributors to the pathology of cancer, neurodegenerative diseases, diabetes, heart diseases, and inflammation. However, studies on the roles of lncRNAs in angiocardiopathy, particularly in cardiac hypertrophy, are still preliminary. In our study, differentially expressed lncRNAs in rat cardiac hypertrophy induced by transverse aortic constriction (TAC) were identified by microarray analysis and validated using quantitative real-time polymerase chain reaction (RT-PCR). Briefly, we identified 6,969 lncRNAs, among which 80 lncRNAs were significantly upregulated and 172 lncRNAs were significantly downregulated. Quantitative RT-PCR was used to validate the differential expression of 5 lncRNAs in myocardial tissue RNA. Further, pathway analysis indicated that 25 pathways corresponded to upregulated transcripts and 20 pathways corresponded to downregulated transcripts. Third, by coexpression network analysis, we found a correlation between BC088254 and phb2 (prohibitin 2) and verified this expression by RT-PCR and Western blot. This is the first study to reveal differentially expressed lncRNAs in rat cardiac hypertrophy induced by TAC, indicating potential lncRNA mechanisms of action in myocardial hypertrophy. We also found that lncRNA BC088254 may have a certain role in myocardial hypertrophy induced by TAC and functional relevance between lncRNA BCO88254 and phb2, but the relationship between these two factors is unclear.

scholarly journals Microarray screening of differentially expressed genes after up-regulating miR-205 or down-regulating miR-141 in cervical cancer cells

2019 ◽  
Author(s):  
Xingyu Fang ◽  
Tingting Yao
Keyword(s):  
Cervical Cancer ◽  
Hela Cell ◽  
Cancer Cells ◽  
Differentially Expressed Genes ◽  
Expression Profile ◽  
Siha Cell ◽  
Differentially Expressed ◽  
Down Regulation ◽  
Siha Cells ◽  
Cervical Cancer Cells

AbstractCervical cancer is one of the most common gynecological malignancies. However,studies on the expression and molecular mechanism of miR-205 and miR-141 in CC are insufficient recently. Expression profile microarray with 21329 Oligo DNA were used to detect the expression of mRNAs in miR-205 up-regulated or miR-141 down-regulated HeLa and SiHa cells and mRNAs in normal HeLa and SiHa cells. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to assess the potential pathways of miR-205 in SiHa cell.Compared with normal HeLa cell, there were 38 differentially expressed genes (DEGs) in miR-205 up-regulated HeLa cell. Nine were up-regulation genes and 29 were down-regulation genes. There were 23 DEGs in miR-141 down-regulated HeLa cell. One was up-regulated and 22 were down-regulated. Compared with normal SiHa cell, there were 128 DEGs in miR-205 up-regulated SiHa cell. One hundred and three were up-regulation genes and 25 were down-regulation genes. There were 80 DEGs in miR-141 down-regulated SiHa cell. Forty two were up-regulation genes and 28 were down-regulation genes. For miR-205 up-regulated SiHa cell, GO outcome showed that “ubiquitin-protein ligase activity”, “MAP kinase phosphatase activity”, were the most enriched terms (P < 0.05). And in KEGG analysis, “Cell cycle” was notably enriched, and Smad4 in this pathway was up-regulated (P < 0.05). Expression profile microarray technology can effectively screen out DEGs in cervical cancer cells after up-regulating miR-205 or down-regulating miR-141. Which may enable us to understand the pathogenesis and lay an important foundation for the prevention and treatment of cervical cancer.

scholarly journals VEGF Contributes to Mesenchymal Stem Cell-Mediated Reversion of Nor1-Dependent Hypertrophy in iPS Cell-Derived Cardiomyocytes

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Denise Philipp ◽  
Michelle Holthaus ◽  
Vida Basoah ◽  
Kurt Pfannkuche ◽  
Laura Suhr ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cardiac Hypertrophy ◽  
Western Blot ◽  
Microarray Analysis ◽  
Heart Diseases ◽  
Orphan Receptor ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Ips Cell ◽  
Hypertrophic Growth

Myocardial hypertrophy is present in many heart diseases, representing a strong predictor of adverse cardiovascular outcomes. Regarding therapeutic intervention, mesenchymal stem cells (MSCs) have been suggested to significantly reduce cardiac hypertrophy and progression to heart failure. Preconditioning of MSCs was previously demonstrated to highly improve their paracrine activity resulting in modulation of immune responses and the progression of diseases. Here, we studied the effects of bone marrow-derived preconditioned MSCs on hypertrophied induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) and also sought to identify MSC-derived antihypertrophic molecules. Phenylephrine (PE) was used to induce hypertrophy in murine iPS-CM, and markers of hypertrophy were identified by microarray analysis. Murine MSCs were treated with IFN-γ and IL-1β to enhance their paracrine activity, and transcriptional profiling was performed by microarray analysis. Hypertrophied iPS-CM were subsequently cocultured with preconditioned MSCs or MSC-conditioned medium (CM), respectively. Effects on hypertrophied iPS-CM were studied by cell area quantification, real-time PCR, and western blot. In some experiments, cells were incubated with fractions of MSC-CM obtained by ultrafiltration or by MSC-CM supplemented with inhibitory antibodies. Intracellular and extracellular levels of vascular endothelial growth factor (VEGF) were evaluated by western blot and ELISA. PE-induced hypertrophy in iPS-CM was associated with an upregulation of neuron-derived orphan receptor (Nor1) expression, activation of Akt, and inhibition of both strongly prevented hypertrophy induction in iPS-CM. VEGF secreted by preconditioned MSCs provoked hypertrophy regression in iPS-CM, and a negative correlation between Nor1 expression and hypertrophic growth could be evidenced. Our results demonstrate that Nor1 expression strongly supports hypertrophy in iPS-CM. Moreover, the secretome of preconditioned MSCs triggered regression of hypertrophy in iPS-CM in a VEGF-dependent manner. We suggest that the delivery of the MSC-derived secretome may represent a therapeutic strategy to limit cardiac hypertrophy. However, additional in vivo studies are needed to prove this hypothesis.

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