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  • 1
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    Abstract 15916: Role of Small-cajal Body Associated RNAs (scaRNAs) in Regulation of Cardiomyogenesis
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Introduction: The requirement of non-coding RNAs particularly scaRNAs are playing a critical role in alternative splicing and maturation of mRNAs. Dysregulated splicing of mRNAs has been shown to cause heart defects. In this study, we are comparing the role of scaRNAs during differentiation of induced pluripotent stem cells (iPSCs) into cardiomyocytes (iCMCs) from normal individual and Noonan syndrome (NS) patient. We have selected NS patient cells because it is an autosomal dominant genetic disorder which leads to cardiomyopathy and congenital heart defects in humans. Hypothesis: We hypothesize that scaRNA1 and scaRNA20 have a significant role in the development of cardiomyocytes, and these scaRNAs are dysfunctional in iCMCs derived from NS. Methods and Results: We have compared the normal skin fibroblast-derived iPSCs (N-iPSCs) and N-iCMCs with NS patient-derived NS-iPSCs and NS-iCMCs using quantitative RT-PCR, Western blot and immunofluorescence analyses. We also used the knockdown and overexpression of scaRNA1 and scaRNA20 approaches to delineate the importance of these scaRNAs during cardiomyogenesis. Our qRT-PCR data showed a significantly lower expression of scaRNA1 and scaRNA20 (Fig. A) as well as the cardiac-specific genes CTT and GATA4 (Fig. B) in NS-iCMCs when compared to the normal iCMCs. Furthermore, the qRT-PCR data from the scaRNA20 overexpressed N-iCMC showed an increased expression of cardiac-specific genes (Fig. C) when compared to the N-iCMCs. These studies clearly indicate that scaRNA1 and scaRNA20 plays an important role in cardiomyogenesis. Further studies are underway to explore the mechanisms of these scaRNAs in regulation of cardiac genes. Conclusions: Our findings indicate that scaRNA1 and scaRNA20 are involved in mRNA splicing and maturation of cardiac genes. Moreover, these scaRNAs are dysfunctional in NS patient’s iCMCs and targeting these molecules will have a therapeutic potential for a patient with NS.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.15916
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 2
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    Abstract 12545: Autologous Induced Mesenchymal Stem Cells-derived Exosomes Exhibit Enhanced Protection Of Cardiomyocytes From Injuries
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Introduction: Mesenchymal stem cells (MSC)-derived exosomes containing small non-coding RNAs (sncRNAs) showed protection of the myocardium from injury, infection, and disease. Recently, we have generated a safe and non-viral method of generating induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) with high replicative, autologous, cardioprotecive potentials, originally derived from human urinary epithelial cells. Hypothesis: We hypothesize that exosomes from iMSC possess a superior cardioprotective, and regenerative characteristics compared to the exosomes from adult umbilical cord MSCs (hereafter referred as MSCs) for the treatment of ischemic cardiomyopathy (ICM). Methods & Results: Exosomes isolated from serum-free conditioned media obtained from iMSCs and MSCs were characterized using Zetasizer, which showed that exosomes from iMSCs had smaller particle size than the MSCs (Fig. A). Exosomal tetraspanin proteins (CD9, CD63 and CD81) were identified by Western blotting. Cardioprotective properties of exosomes were evaluated using functional iPSC-derived cardiomyocytes (iCMCs), which were treated with 50 μg of exosomes 1 hr before subjecting them to either 24 hrs of Ang II treatment (10 μM) or 6 hrs of 1% hypoxia and 24 hrs of reoxygenation. The exosomes from iMSCs elicited a superior cardioprotective characteristic studied through qRT-PCR expression of survival genes and measurement of mitochondrial membrane potentials (JC1 dye), intracellular reactive oxygen species (CM-H2DCFDA), and in situ cell death by apoptosis (Fig. B) when compared to the exosomes from MSCs. Furthermore, the expressions of injury-associated sncRNAs such as SNORD32a, SNORD33, and SNORD35a were identified in both exosomes. Conclusions: In comparison with the exosomes of available MSCs, exosomes from iMSCs showed an enhanced protection of cardiomyocytes from injuries and can be a valuable cell-free source for the treatment of ICM.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.12545
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 3
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    Abstract 515: Non-invasive Method of Generating Human Induced-mesenchymal Stem Cells Derived From Urinary Epithelial Cells for Regenerative Therapy
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Research Vol. 127, No. Suppl_1 ( 2020-07-31)
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 127, No. Suppl_1 ( 2020-07-31)
    Abstract: Introduction: Mesenchymal stem cells (MSCs) are multipotent adult stem cells having an extensive proliferation capacity in vitro and in vivo. These MSCs can differentiate into various mesoderm-type cells such as osteoblasts, cardiomyocytes, etc. A subpopulation of urinary epithelial cells (UECs) have been identified in urine samples, is considered a promising cell resource for generating autologous induced-pluripotent stem cells (iPSCs). Hypothesis: We hypothesize that the production of high quality, autologous, induced-MSCs (iMSCs) with high replicative potential suitable for the regenerative therapy, using an easy, and the most non-invasive method of isolation, from human UECs. Methods and Results: Human urine was collected and centrifuged to obtain the UECs, which were characterized by the expression of CK19 and ZO1. These UECs were reprogrammed to iPSCs using a cocktail of mRNAs (OCT4, KLF4, SOX2, c-MYC, Nanog and Lin28) along with Lipofectamine for 11 days in culture. These iPSCs were characterized by the expression of the pluripotent markers such as OCT4, SOX2 and SSEA4. The iPSCs were subsequently differentiated into iMSCs using the mesenchymal specific medium for 21 days. iMSCs were harvested at the end of 21 days, and they were characterized by the high levels of mRNA and protein expressions of mesenchymal specific markers such as CD73, CD90 and CD105 (Fig. 1A). FACS analysis showed that more than 93% of the cells were positive for the markers of MSCs (Fig. 1B) . Moreover, the obtained iMSCs have high proliferation capacity compared with the adult stem cells. Conclusions: We have developed an easy, non-invasive method for obtaining autologous, non-immunogenic and highly-proliferating iMSCs suitable for various regenerative therapies including cardiac diseases, from urinary epithelial cells.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/res.127.suppl_1.515
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 4
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    Abstract 12841: Overexpression of Scarna20 Promotes Small Nuclear RNA Pseudouridylation and Improves Cardiomyogenesis
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 146, No. Suppl_1 ( 2022-11-08)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. Suppl_1 ( 2022-11-08)
    Abstract: Introduction: Non-coding RNAs, particularly small Cajal body-associated RNAs (scaRNAs), play an important role in alternative splicing and maturation of mRNAs through pseudouridylatory modification. Our small non-coding RNA sequencing analysis has identified that scaRNA20 plays a major role in cardiomyocyte differentiation. In this study, we aim to elucidate the role of scaRNA20 during cardiac differentiation using in vitro induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMC) subjected to 3% hypoxic conditions. Hypothesis: Overexpression (OE) of scaRNA20 in iPSCs leads to enhanced cardiomyogenesis and increases the endurance properties of cardiomyocytes by maintaining contractility under hypoxic conditions. Methods and results: We have used OE and knockdown (KD) assays to delineate the role of scaRNA20 during the process of iPSC to iCMC differentiation. The video recordings of scaRNA20-OE-iCMCs and scaRNA20-KD-iCMC contractilities were measured by a novel Particle Image Velocimetry (PIV) method. Our results show that the contractility was impaired in control iCMCs whereas in scaRNA20-OE-iCMCs it was well-maintained under the hypoxic conditions. In contrast, scaRNA20-KD-iCMCs resulted in poor differentiation, they were non-functional and had an impaired contractility. Furthermore, we investigated the pseudouridylation levels of spliceosomal RNA U12 which is a direct target for scaRNA20. We found an increased level of Ψ 28 in scaRNA20-OE iCMCs (Figure A-D) . In addition, the scaRNA20 overexpression in iCMCs resulted in the upregulation of DKC1, NHP2, and NOP10 and downregulation of GAR1, COIL, and WRAP53 and these effects regulate the activation of pTP53 and STAT3 and thus activating cardiac genes. Conclusion: Taken together, our results show for the first time that modulation of iCMCs with scaRNA20 helps maintain the endurance properties of cardiomyocytes while under hypoxic conditions, and it also improves cardiomyogenesis.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.146.suppl_1.12841
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 5
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    Abstract 17035: Inhibition of DNMT and HDAC6 Together Regulates Macrophage Polarization by FoxO1-HIF2α Signaling and Protects Endotoxemia-Induced Inflammation
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Circulation Vol. 138, No. Suppl_1 ( 2018-11-06)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 138, No. Suppl_1 ( 2018-11-06)
    Abstract: Introduction: Acute lung injury (ALI) is a common pulmonary disease caused by bacterial infection leading to an imbalance between pro-inflammatory and anti-inflammatory immune responses. Studies have shown that macrophage polarization (M1 and M2) during ALI plays a key role in regulating these responses. Hypothesis: We hypothesized that combined treatment with 5-Aza 2-deoxycytidine (Aza) + tubastatin A (TBA) would reduce inflammation and promote an anti-inflammatory M2 macrophage phenotype by regulating the HIF2α signaling pathway. Methods: To show the effect of Aza+TBA, lipopolysaccharide (LPS)-induced macrophages (RAW 264.7) were treated with either Aza (50nM), TBA n(750nM), or together (Aza+TBA) for 24 hours. The mRNA and protein expressions of FoxO1, HIF2α, NOS2 (M1), and CD206 (M2) were measured by qRT-PCR and Western analyses in lung tissue and macrophages. Results: Our results revealed that LPS induced macrophages showed an increased expression of NOS2 (M1) and decreased expression of Fizz-1 (M2) whereas the LPS-induced macrophages were treated with Aza+TBA showed decreased NOS2 (Fig. A) and increased Fizz-1 mRNA (Fig. B) and protein expressions. Furthermore, the LPS significantly decreased the mRNA and protein expressions of FoxO1 and HIF2α in macrophages. These expressions were significantly increased when the LPS-induced macrophages were treated with Aza +TBA (Fig. C) . These results suggest that Aza+TBA treatment together generates more M2 macrophages there by reducing the LPS-induced inflammatory responses. Conclusions: Overall, these data show the first time that the combinatorial treatment with Aza+TBA regulates macrophage cell polarization and abrogates LPS-induced inflammation through FoxO1-HIF2α signaling pathway. Thus, epigenetic modifiers may be potential therapeutic drugs for ALI. 〈 !--EndFragment-- 〉
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.138.suppl_1.17035
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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  • 6
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    Abstract 13305: Impact of Small Cajal-Body Associated RNAs in IPSC-Derived Cardiomyocytes From Progeria and Noonan Patients
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 146, No. Suppl_1 ( 2022-11-08)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. Suppl_1 ( 2022-11-08)
    Abstract: Introduction: Progeria and Noonan syndrome are major genetic disorders that impact the cardiovascular system and lead to congenital heart defects in children. The small Cajal body-associated RNAs (scaRNAs) are a class of H/ACA box non-coding RNAs, which play an important role in the biochemical modification of spliceosomal RNAs and contribute to alternative splicing and maturation of mRNAs. In this study, we aim to elucidate the role of scaRNAs during cardiac differentiation and its effect in Progeria and Noonan Patients-derived induced pluripotent stem cell-derived cardiomyocytes (iCMC). Hypothesis: We hypothesize that scaRNAs have a significant role in cardiac development and are associated with cardiovascular development in disease conditions. Methods and Results: To elucidate the role of scaRNAs in Noonan and Progeria patients during cardiomyogenesis, we differentiated iCMCs from iPSCs generated from Noonan (c.1654A 〉 G) and Progeria (c.1824 C 〉 T) patients. The differential expression of scaRNAs was performed by qRT-PCR and the result shows that scaRNA6, scaRNA11, scaRNA14 scaRNA20, and scaRNA28 were significantly reduced in Noonan and Progeria patients iCMC compared to normal skin fibroblast (SF)-derived iCMCs and Urinary epithelial cells (UE)-derived iCMC (Fig.1). The mRNA expression of the cardiac-specific gene in Progeria and Noonan patient-derived iCMC was significantly reduced when compared with normal iCMC. Furthermore, the scaRNA overexpressed normal iCMCs (scaRNA20-OE-iCMCs) showed significantly increased cardiac-specific mRNA and protein expressions when compared with control iCMC (Figs.2 & 3) . Conclusion: Our finding indicates that scaRNAs have major impacts on Noonan and Progeria patient-derived iCMC. Targeting the scaRNAs will have efficient therapeutic potential for Noonan and Progeria patients.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.146.suppl_1.13305
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 7
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    Abstract 21256: Cardiac ECM Environment Improves iPSC-Derived Cardiomyocyte Differentiation
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation Vol. 136, No. suppl_1 ( 2017-11-14)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 136, No. suppl_1 ( 2017-11-14)
    Abstract: Introduction: Generation of induced pluripotent stem cells (iPSCs) and their differentiation into cardiomyocytes (CMCs) have created exciting possibilities in cardiac medicine. However, the long-term impact of iPSC-derived CMC implantation on cardiac function remains elusive. After the first month following injection, only less than 10% of the implanted cells remain alive. In contrast, during development mesodermal precursors differentiate into a functional myocardium without substantial cell loss. Hypothesis: The poor survival of iPSC-derived CMCs is mainly attributable to the lack of evolutionarily determined microenvironment in which the normal differentiation process takes place. Thus, we hypothesize that the embryonic or adult heart-derived extracellular matrix (ECM) provides a better culture environment for CMC differentiation. Methods: We utilized a highly efficient, viral-free combination of DNA and mRNA transcription factor approach to generate iPSCs and functional CMCs from adult human cells. To analyze CMC contractility, we recorded cultures using both time-lapse and high frame-rate video microscopy. ECM from adult and embryonic chicken hearts was extracted using a high salt/urea protocol, and lyofilized. iPSCs were grown on a variety of substrates, including rehydrated cardiac ECM or electrospinned films. The quality of differentiation was characterized by molecular markers, electron microscopy and tracking beat frequencies. Results: Heart ECM extracts provide a supportive environment for CMC differentiation. When grown on ECM extracted from adult chicken hearts, the maturation of iPSCs-derived cardiomyocytes exceeds those that were cultured using matrigel environments. For example, in vitro beat rates are higher on heart ECM (Figure, red symbols) than on matrigel (black). Conclusions: Culture environments containing heart-derived matrix is a promising avenue to improve the quality of iPSC-derived cardiomyocytes.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.136.suppl_1.21256
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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  • 8
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    Abstract 13176: Overexpression of BANF1 is Linked to Cardiac Pathologies in Progeria Patients
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 146, No. Suppl_1 ( 2022-11-08)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. Suppl_1 ( 2022-11-08)
    Abstract: Introduction: Hutchinson-Gilford progeria (HGP) is a genetic disorder caused by a single nucleotide mutation in the Lamin A gene. This mutation causes the production of the abnormal lamin A protein called progerin. Children affected by this disorder age rapidly and die at an early age, mostly from cardiac pathologies. Another similar progeroid syndrome is Nestor-Guillermo progeria, in which the patients exhibit accelerated aging but have a longer life span. This latter syndrome is caused by a mutation that silences the BANF1 gene. Hypothesis: We hypothesize that BANF1 is linked to cardiovascular disease in Hutchinson-Gilford progeria patients. This gene could be targeted to reduce cardiac pathologies and increase the lifespan of patients with HGP. Methods: We obtained skin fibroblasts from two HGP patients and their respective parents from the Progeria Foundation. We successfully reprogrammed the fibroblasts into induced pluripotent stem cells by a safe non-viral method and further differentiated them into induced cardiomyocytes (iCMCs). Then, we performed multiple analyses to compare the iCMCs of the patients, their parents, and control iCMCs. Results: Through in-silico protein analysis, we were able to identify a relationship between nuclear lamina proteins and BANF1, which is also correlated to cardiac-specific proteins GATA4 and NKX2.5 ( Figure A ). Additionally, through qPCR ( Figure B ) and Western Blot ( Figure C ) analyses, we identified a significant difference in BANF1 expression between the progeria patient iCMCs and the other iCMCs. BANF1 was overexpressed in patient iCMCs, whereas, it had normal expression in patient fibroblasts when compared to control cells. Conclusions: We believe that BANF1 could be a good target for future therapeutic approaches to minimize cardiac pathologies in HGP patients and extend their lifespan.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.146.suppl_1.13176
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 9
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    Abstract 502: Inhibition of Histone Deacetylase 6 Protects Human Induced Pluripotent Stem Cells-derived Cardiomyocytes Through Inhibition of Autophagy
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Research Vol. 127, No. Suppl_1 ( 2020-07-31)
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 127, No. Suppl_1 ( 2020-07-31)
    Abstract: Introduction: Autophagy is known to play an important role in mediating cardiac hypertrophy. However, the mechanism is poorly understood. Since the protein histone deacetylase 6 (HDAC6) contributes to cardiac dysfunction in response to angiotensin II (AngII) signaling, we have examined the role of HDAC6 inhibitor tubastatin A (TBA) in AngII-induced remodeling in human induced pluripotent stem cells-derived cardiomyocytes (iCMCs). Hypothesis: We hypothesize that the inhibition of HDAC6 protects iCMCs from AngII-induced cardiac hypertrophy through inhibition of autophagy. Methods and Results: We have generated and characterized induced pluripotent stem cells from human adult skin fibroblasts and subsequently differentiated them into iCMCs. Treatment with 10 μM angiotensin II for 24 hrs increased the HDAC6 activity and lead to hypertrophy in iCMCs. The AngII-induced hypertrophy, and the excessive contractility in iCMCs were reversed by the inhibition of HDAC6 with TBA (1 μM for 24 hours). The number of LC3-positive iCMCs, and the mRNA and the protein expression of autophagic genes Beclin-1, LC3, and p62 were increased by the presence of AngII, and the anti-autophagic gene Bcl2 was decreased by AngII. The inhibition of HDAC6 with TBA reversed the AngII-mediated changes in the autophagic genes expressions in iCMCs. Autophagic vacuoles were identified with monodansylcadaverine (MDC, green) and lysosomes with LysoTracker (red) (Fig. 1A) . The number of autophagolysosomes were increased by AngII, and this was decreased with TBA in iCMCs (Fig. 1B) . Conclusions: Our report indicates for the first time that the AngII-induced cardiac hypertrophy-mediated autophagy is effectively inhibited by the suppression of HDAC6 in human iCMCs.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/res.127.suppl_1.502
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 10
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    Abstract 489: Identification And In-silico Analysis Of Pathogenic Non-synonymous Snps Of Human Sos1 Protein In Noonan Syndrome
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Research Vol. 127, No. Suppl_1 ( 2020-07-31)
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 127, No. Suppl_1 ( 2020-07-31)
    Abstract: Introduction: Noonan syndrome is a genetic disorder (autosomal dominant) characterized by short stature, congenital heart disease, bleeding problems, developmental delays, and skeletal malformation. It is mainly caused by a single nucleotide alteration in four genes PTPN11, SOS1, RAF1, and KRAS . In this study, we computationally analyzed the SOS1 gene to identify the pathogenic non-synonymous single nucleotide polymorphisms (nsSNPs), which is known to cause Noonan syndrome. Hypothesis: We hypothesize that in-silico analysis of human SOS1 mutations in Noonan syndrome would be a promising predictor to study the post-translational modifications. Methods and Results: The variant information of SOS1 was collected from the dbSNP database and the literature review on Noonan syndrome. They were further analyzed by in-silico tools such as I-Mutant, iPTREE-STAB, and MutPred for their structural and functional properties. We found that 11 nsSNPs are more pathogenic for Noonan syndrome. The 3D comparative protein of 11 nsSNPs with its wild-type SOS1 was modeled by using I-Tasser and validated via ERRAT and RAMPAGE. The protein-protein interactions of SOS1, GATA4, TNNT2, and ACTN2 were analyzed using STRING, which showed that HRAS was intermediate between SOS1 and ACTN2 (Fig. 1) . Conclusion: This is the first in-silico study of the SOS1 variant with Noonan syndrome. We proposed that this 11 nsSNPs are the most pathogenic variant of SOS1 , which helps to screen the Noonan patient. Furthermore, our results are promising to study the gain/loss of post-translational modification (PTM) by mutation in cardiac genes and helps to explore the novel molecular pathways.$graphic_{DB5B0E7D-4DA6-4569-A16F-E05B2C9C4D2F}$$
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/res.127.suppl_1.489
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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