Long non-coding RNAs in Heart Failure: A Deep Belief Network based Cluster Analysis

Current Bioinformatics ◽

10.2174/1574893616666210528162945 ◽

2021 ◽

Vol 16 ◽

Author(s):

Manu Madhavan ◽

Gopakumar G

Keyword(s):

Heart Failure ◽

Cluster Analysis ◽

Topic Model ◽

Functional Module ◽

Deep Belief Network ◽

Messenger Rnas ◽

Belief Network ◽

Network Cluster ◽

Micro Rnas ◽

Non Coding Rnas

Background: Heart failure (HF) is a leading cause of mortality rate worldwide, but studied less for its underlying biomolecular mechanisms. With the advances in gene sequence analysis, many non-coding RNAs, especially from long non-coding RNA (lncRNA) genre are found to be involved in regulating HF conditions. Recent studies are based on competing endogenous RNA (ceRNA) theory in which lncRNA-miRNA-mRNA compounds control many disease conditions. Method: In this paper, we present a topic model based network cluster analysis to identify the role of lncRNAs in HF. The network is constructed based on the differentially expressed long non-coding RNAs (lncRNAs), micro RNAs (miRNAs), and messenger RNAs (mRNAs) of heart failure patients and control samples from the gene expression omnibus (GEO) database. Further, we extend the primary ceRNA network by adding pathways as additional nodes. Deep belief network based feature learning is used to extract the features from the network automatically. Results: We obtained two clusters where each cluster was a mixture of lncRNAs, mRNAs, miRNAs and pathways. The analysis included the identification of key lncRNAs, enriched pathways, and gene ontology terms from each cluster. Based on the shreds of evidence from literature, one of the clusters obtained was identified to be an essential functional module in HF mechanism. The potential of lncRNA as a diagnostic biomarker in HF was also analysed.

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P318Exosomes mediate myocardial regeneration of cardiac progenitor cells in a swine model of dilated cardiomyopathy

European Heart Journal ◽

10.1093/eurheartj/ehz747.0153 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

K Hirai ◽

T Goto ◽

D Ousaka ◽

S Ohtsuki ◽

H Oh

Keyword(s):

Heart Failure ◽

Therapeutic Efficacy ◽

Swine Model ◽

Cardiac Progenitor Cells ◽

Messenger Rnas ◽

Bioactive Substances ◽

Serious Adverse Events ◽

Paracrine Factors ◽

Micro Rnas ◽

Picrosirius Red

Abstract Introduction Stem cell therapy has been shown to improve cardiac function. The mechanisms of therapeutic efficacy are considered the secretion of paracrine factors but the details are still unknown. Hypothesis Exosomes are extracellular vesicles containing bioactive substances such as proteins, messenger RNAs and micro RNAs. We hypothesized that exosomes may be the main paracrine factors to mediate therapeutic efficacy of cardiosphere-derived cells (CDCs). Methods Farm pigs (30 kg, n=10) were treated by intracoronary administration of 10,000 microspheres (100–300 μm) into three vessels. Two weeks later, 9.0×106 CDCs pretreated by exosome inhibitor (EI; 20μM of GW4869) or DMSO as controls were selectively infused into three coronary arteries. Evaluation of ejection fraction (EF) was performed before cell infusion and 1 month after protocol treatment. Results Pigs developed diffuse hypokinetic heart failure (baseline EF 37.1%±2.1%) and randomly assigned into two groups (CDCs with EI: n=5, CDCs with DMSO: n=5). No serious adverse events were found during the CDCs infusion. Significant improvement of EF was observed in CDCs with DMSO group (37.1%±2.1% to 42.5%±3.0%; P=0.01), whereas no change was found in CDCs with EI group (37.1%±2.4% to 36.2%±2.9%; P=0.58). Myocardial fibrosis stained by picrosirius red was significantly reduced in CDCs with DMSO group compared with CDCs with EI group (9.5±3.6% versus 17.3±5.3%; P<0.01). Conclusions We confirmed the therapeutic efficacy of CDCs and these effects were mainly mediated by exosomes.

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Significance of non-coding circular RNAs and micro RNAs in the pathogenesis of cardiovascular diseases

Journal of Medical Genetics ◽

10.1136/jmedgenet-2018-105387 ◽

2018 ◽

Vol 55 (11) ◽

pp. 713-720 ◽

Cited By ~ 6

Author(s):

Guoan Zhao

Keyword(s):

Heart Failure ◽

Cardiovascular Diseases ◽

Regulation Of Gene Expression ◽

Renin Angiotensin System ◽

Genomic Research ◽

Circular Rnas ◽

Surgical Interventions ◽

Novel Treatments ◽

Micro Rnas ◽

Non Coding Rnas

Heart failure, coronary artery disease and myocardial infarction are the most prominent cardiovascular diseases contributing significantly to death worldwide. In the majority of situations, except for surgical interventions and transplantation, there are no reliable therapeutic approaches available to address these health problem. Despite several advances that led to the development of biomarkers and therapies based on the renin–angiotensin system, adrenergic pathways, etc, more definitive and consistent biomarkers and specific target based molecular therapies are still being sought. Recent advances in the field of genomic research has helped in identifying non-coding RNAs, including circular RNAs, piRNAs, micro RNAs, and long non-coding RNAs, that play a significant role in the regulation of gene expression and function and have direct impact on pathophysiological mechanisms. This new knowledge is currently being explored with much hope for the development of novel treatments and biomarkers. Circular RNAs and micro RNAs have been described in myocardium and aortic valves and were shown to be involved in the regulation of pathophysiological processes that potentially contribute to cardiovascular diseases. Approximately 32 000 human exonic circular RNAs have been catalogued and their functions are still being ascertained. In the heart, circular RNAs were shown to bind micro RNAs in a specific manner and regulate the expression of transcription factors and stress response genes, and expression of these non-coding RNAs were found to change in conditions such as cardiac hypertrophy, heart failure and cardiac remodelling, reflecting their significance as diagnostic and prognostic biomarkers. In this review, we address the present state of understanding on the biogenesis, regulation and pathophysiological roles of micro and circular RNAs in cardiovascular diseases, and on the potential future perspectives on their use as biomarkers and therapeutic agents.

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Biological activity of mesenchymal stem cells secretome as a basis for cell-free therapeutic approach

Research Results in Pharmacology ◽

10.3897/rrpharmacology.6.49413 ◽

2020 ◽

Vol 6 (1) ◽

pp. 57-68 ◽

Cited By ~ 2

Author(s):

Liubov A. Pokrovskaya ◽

Ekaterina V. Zubareva ◽

Sergey V. Nadezhdin ◽

Anna S. Lysenko ◽

Tatyana L. Litovkina

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stromal Cells ◽

Adult Stem Cells ◽

Neuroprotective Effect ◽

Biologically Active ◽

Adipose Derived Stem Cells ◽

Messenger Rnas ◽

Micro Rnas ◽

Non Coding Rnas

Mesenchymal stem (stromal) cells (MSCs) are self-renewing, cultured adult stem cells which secrete a complex set of multiple soluble biologically active molecules such as chemokines, and cytokines, cell adhesion molecules, lipid mediators, interleukins (IL), growth factors (GFs), hormones, micro RNAs (miRNAs), long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), exosomes, as well as microvesicles, the secretome. MSCs of various origin, including adipose-derived stem cells (ASCs), bone marrow derived mesenchymal stem cells (BM-MSCs), human uterine cervical stem cells (hUCESCs), may be good candidates for obtaining secretome-derived products. Different population of MSCs can secret different factors which could have anti-inflammatory, anti-apoptotic, anti-fibrotic activities, a neuroprotective effect, could improve bone, muscle, liver regeneration and wound healing. Therefore, the paracrine activity of conditioned medium obtained when cultivating MSCs, due to a plethora of bioactive factors, was assumed to have the most prominent cell-free therapeutic impact and can serve as a better option in the field of regenerative medicine in future.

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