MicroRNA-425 and microRNA-155 cooperatively regulate atrial natriuretic peptide expression and cGMP production.
AIMS:Atrial natriuretic peptide (ANP), secreted primarily by atrial cardiomyocytes, decreases blood pressure by raising cyclic 3',5'-guanosine monophosphate (cGMP) levels and inducing vasorelaxation, natriuresis, and diuresis. Raising the level of ANP has been shown to be an effective trea...
| 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/PMC5919659?pdf=render |
| _version_ | 1818258655323095040 |
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| author | Sara Vandenwijngaert Clara D Ledsky Obiajulu Agha Connie Wu Dongjian Hu Aranya Bagchi Ibrahim J Domian Emmanuel S Buys Christopher Newton-Cheh Donald B Bloch |
| author_facet | Sara Vandenwijngaert Clara D Ledsky Obiajulu Agha Connie Wu Dongjian Hu Aranya Bagchi Ibrahim J Domian Emmanuel S Buys Christopher Newton-Cheh Donald B Bloch |
| author_sort | Sara Vandenwijngaert |
| collection | DOAJ |
| description | AIMS:Atrial natriuretic peptide (ANP), secreted primarily by atrial cardiomyocytes, decreases blood pressure by raising cyclic 3',5'-guanosine monophosphate (cGMP) levels and inducing vasorelaxation, natriuresis, and diuresis. Raising the level of ANP has been shown to be an effective treatment for hypertension. To advance the future development of an anti-microRNA (miR) approach to increasing expression of ANP, we investigated the regulation of NPPA expression by two miRs: miR-425 and miR-155. We examined whether miR-425 and miR-155 have an additive effect on the expression and function of ANP. METHODS AND RESULTS:Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were transfected with miR-425, miR-155, or a combination of the two miRs. Two days later, NPPA expression was measured using real time qPCR. Each of the miRs decreased NPPA expression over a wide range of concentrations, with a significant reduction at concentrations as low as 1 nM. The combination of miR-425 and miR-155 reduced NPPA expression to a greater extent than either miR-425 or miR-155 alone. An in vitro assay was developed to study the potential biological significance of the miR-induced decrease in NPPA expression. The cooperative effect of miR-425 and miR-155 on NPPA expression was associated with a significant decrease in cGMP levels. CONCLUSIONS:These data demonstrate that miR-425 and miR-155 regulate NPPA expression in a cooperative manner. Targeting both miRNAs with anti-miRs (possibly at submaximal concentrations) might prove to be a more effective strategy to modulate ANP levels, and thus blood pressure, than targeting either miRNA alone. |
| first_indexed | 2024-12-12T18:03:00Z |
| format | Article |
| id | doaj.art-ff409b7d9fee48ebac90a5ce6565663a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T18:03:00Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ff409b7d9fee48ebac90a5ce6565663a2022-12-22T00:16:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01134e019669710.1371/journal.pone.0196697MicroRNA-425 and microRNA-155 cooperatively regulate atrial natriuretic peptide expression and cGMP production.Sara VandenwijngaertClara D LedskyObiajulu AghaConnie WuDongjian HuAranya BagchiIbrahim J DomianEmmanuel S BuysChristopher Newton-ChehDonald B BlochAIMS:Atrial natriuretic peptide (ANP), secreted primarily by atrial cardiomyocytes, decreases blood pressure by raising cyclic 3',5'-guanosine monophosphate (cGMP) levels and inducing vasorelaxation, natriuresis, and diuresis. Raising the level of ANP has been shown to be an effective treatment for hypertension. To advance the future development of an anti-microRNA (miR) approach to increasing expression of ANP, we investigated the regulation of NPPA expression by two miRs: miR-425 and miR-155. We examined whether miR-425 and miR-155 have an additive effect on the expression and function of ANP. METHODS AND RESULTS:Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were transfected with miR-425, miR-155, or a combination of the two miRs. Two days later, NPPA expression was measured using real time qPCR. Each of the miRs decreased NPPA expression over a wide range of concentrations, with a significant reduction at concentrations as low as 1 nM. The combination of miR-425 and miR-155 reduced NPPA expression to a greater extent than either miR-425 or miR-155 alone. An in vitro assay was developed to study the potential biological significance of the miR-induced decrease in NPPA expression. The cooperative effect of miR-425 and miR-155 on NPPA expression was associated with a significant decrease in cGMP levels. CONCLUSIONS:These data demonstrate that miR-425 and miR-155 regulate NPPA expression in a cooperative manner. Targeting both miRNAs with anti-miRs (possibly at submaximal concentrations) might prove to be a more effective strategy to modulate ANP levels, and thus blood pressure, than targeting either miRNA alone.http://europepmc.org/articles/PMC5919659?pdf=render |
| spellingShingle | Sara Vandenwijngaert Clara D Ledsky Obiajulu Agha Connie Wu Dongjian Hu Aranya Bagchi Ibrahim J Domian Emmanuel S Buys Christopher Newton-Cheh Donald B Bloch MicroRNA-425 and microRNA-155 cooperatively regulate atrial natriuretic peptide expression and cGMP production. PLoS ONE |
| title | MicroRNA-425 and microRNA-155 cooperatively regulate atrial natriuretic peptide expression and cGMP production. |
| title_full | MicroRNA-425 and microRNA-155 cooperatively regulate atrial natriuretic peptide expression and cGMP production. |
| title_fullStr | MicroRNA-425 and microRNA-155 cooperatively regulate atrial natriuretic peptide expression and cGMP production. |
| title_full_unstemmed | MicroRNA-425 and microRNA-155 cooperatively regulate atrial natriuretic peptide expression and cGMP production. |
| title_short | MicroRNA-425 and microRNA-155 cooperatively regulate atrial natriuretic peptide expression and cGMP production. |
| title_sort | microrna 425 and microrna 155 cooperatively regulate atrial natriuretic peptide expression and cgmp production |
| url | http://europepmc.org/articles/PMC5919659?pdf=render |
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