MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy.
MicroRNAs (miRNAs) may serve as elegant tool to improve risk stratification in bicuspid aortic valve (BAV)-associated aortopathy. However, the exact pathogenetic pathway by which miRNAs impact aortopathy progression is unknown. Herewith, we aimed to analyze the association between circulating miRNAs...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6066209?pdf=render |
| _version_ | 1828492095302664192 |
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| author | Evaldas Girdauskas Johannes Petersen Niklas Neumann Martin Ungelenk Ingo Kurth Hermann Reichenspurner Tanja Zeller |
| author_facet | Evaldas Girdauskas Johannes Petersen Niklas Neumann Martin Ungelenk Ingo Kurth Hermann Reichenspurner Tanja Zeller |
| author_sort | Evaldas Girdauskas |
| collection | DOAJ |
| description | MicroRNAs (miRNAs) may serve as elegant tool to improve risk stratification in bicuspid aortic valve (BAV)-associated aortopathy. However, the exact pathogenetic pathway by which miRNAs impact aortopathy progression is unknown. Herewith, we aimed to analyze the association between circulating miRNAs and rare variants of aortopathy-related genes. 63 BAV patients (mean age 47.3±11.3 years, 92% male) with a root dilatation phenotype, who underwent aortic valve+/-proximal aortic surgery at a single institution (mean post-AVR follow-up 10.3±6.9 years) were analyzed. A custom-made HaloPlex HS panel including 20 aortopathy-related genes was used for the genetic testing. miRNAs were extracted from whole blood and miRNA analysis was performed using miRNA-specific assay. Study endpoint was the association between circulating miRNAs and rare genetic variants in the aortopathy gene panel. The study cohort was divided into a subgroup with rare variants vs. a subgroup without rare variants based on the presence of rare variants in the respective genes (i.e., at least one variant present). The genetic analysis yielded n = 6 potentially and likely pathogenic rare variants within the NOTCH1 gene as being the most common finding. Univariate analysis between blood miRNAs and NOTCH1 variants revealed a significantly lower expression of miR-145 in the subgroup of patients with NOTCH1 variants vs. those without NOTCH1 variants (i.e., delta Ct 4.95±0.74 vs. delta Ct 5.57±0.78, p = 0.04). Our preliminary data demonstrate a significant association between blood miR-145 expression and the presence of rare NOTCH1 variants. This association may be indicative of a specific pathogenetic pathway in the development of genetically-triggered bicuspid aortopathy. |
| first_indexed | 2024-12-11T11:14:31Z |
| format | Article |
| id | doaj.art-66a5b626173147b4884e8060d5037c59 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T11:14:31Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-66a5b626173147b4884e8060d5037c592022-12-22T01:09:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01137e020020510.1371/journal.pone.0200205MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy.Evaldas GirdauskasJohannes PetersenNiklas NeumannMartin UngelenkIngo KurthHermann ReichenspurnerTanja ZellerMicroRNAs (miRNAs) may serve as elegant tool to improve risk stratification in bicuspid aortic valve (BAV)-associated aortopathy. However, the exact pathogenetic pathway by which miRNAs impact aortopathy progression is unknown. Herewith, we aimed to analyze the association between circulating miRNAs and rare variants of aortopathy-related genes. 63 BAV patients (mean age 47.3±11.3 years, 92% male) with a root dilatation phenotype, who underwent aortic valve+/-proximal aortic surgery at a single institution (mean post-AVR follow-up 10.3±6.9 years) were analyzed. A custom-made HaloPlex HS panel including 20 aortopathy-related genes was used for the genetic testing. miRNAs were extracted from whole blood and miRNA analysis was performed using miRNA-specific assay. Study endpoint was the association between circulating miRNAs and rare genetic variants in the aortopathy gene panel. The study cohort was divided into a subgroup with rare variants vs. a subgroup without rare variants based on the presence of rare variants in the respective genes (i.e., at least one variant present). The genetic analysis yielded n = 6 potentially and likely pathogenic rare variants within the NOTCH1 gene as being the most common finding. Univariate analysis between blood miRNAs and NOTCH1 variants revealed a significantly lower expression of miR-145 in the subgroup of patients with NOTCH1 variants vs. those without NOTCH1 variants (i.e., delta Ct 4.95±0.74 vs. delta Ct 5.57±0.78, p = 0.04). Our preliminary data demonstrate a significant association between blood miR-145 expression and the presence of rare NOTCH1 variants. This association may be indicative of a specific pathogenetic pathway in the development of genetically-triggered bicuspid aortopathy.http://europepmc.org/articles/PMC6066209?pdf=render |
| spellingShingle | Evaldas Girdauskas Johannes Petersen Niklas Neumann Martin Ungelenk Ingo Kurth Hermann Reichenspurner Tanja Zeller MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy. PLoS ONE |
| title | MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy. |
| title_full | MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy. |
| title_fullStr | MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy. |
| title_full_unstemmed | MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy. |
| title_short | MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy. |
| title_sort | mir 145 expression and rare notch1 variants in bicuspid aortic valve associated aortopathy |
| url | http://europepmc.org/articles/PMC6066209?pdf=render |
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