Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression
Abstract Angiogenesis is a multi-factorial physiological process deregulated in human diseases characterised by excessive or insufficient blood vessel formation. Emerging evidence highlights a novel role for microRNAs as regulators of angiogenesis. Previous studies addressing the effect of miR-133a...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-08-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-19172-x |
| _version_ | 1798032292038311936 |
|---|---|
| author | Suhail Ahmed Sathishkumar Kurusamy Ezra Leander Santhosh David Kinza Khan Krithika Kalyanakrishnan Miebaka Ian-Gobo Teja Manidhar Kola Robert N. Wilkinson Vinodh Kannappan Weiguang Wang Manuel J. Gómez Juan Miguel Redondo James Cotton Angel L. Armesilla |
| author_facet | Suhail Ahmed Sathishkumar Kurusamy Ezra Leander Santhosh David Kinza Khan Krithika Kalyanakrishnan Miebaka Ian-Gobo Teja Manidhar Kola Robert N. Wilkinson Vinodh Kannappan Weiguang Wang Manuel J. Gómez Juan Miguel Redondo James Cotton Angel L. Armesilla |
| author_sort | Suhail Ahmed |
| collection | DOAJ |
| description | Abstract Angiogenesis is a multi-factorial physiological process deregulated in human diseases characterised by excessive or insufficient blood vessel formation. Emerging evidence highlights a novel role for microRNAs as regulators of angiogenesis. Previous studies addressing the effect of miR-133a expression in endothelial cells during blood vessel formation have reported conflicting results. Here, we have assessed the specific effect of mature miR-133a strands in angiogenesis and the expression of endothelial angiogenic genes. Transfection of miR-133a-3p or -5p mimics in primary human endothelial cells significantly inhibited proliferation, migration, and tubular morphogenesis of transfected cells. Screening of gene arrays related to angiogenic processes, and further validation by TaqMan qPCR, revealed that aberrant expression of miR-133a-3p led to a decrease in the expression of genes encoding pro-angiogenic molecules, whilst increasing those with anti-angiogenic functions. Ingenuity Pathway Analysis of a collection of genes differentially expressed in cells harbouring miR-133a-3p, predicted decreased cellular functions related to vasculature branching and cell cycle progression, underlining the inhibitory role of miR-133a-3p in angiogenic cellular processes. Our results suggest that controlled delivery of miR-133a-3p mimics, or antagomirs in diseased endothelial cells, might open new therapeutic interventions to treat patients suffering from cardiovascular pathologies that occur with excessive or insufficient angiogenesis. |
| first_indexed | 2024-04-11T20:11:45Z |
| format | Article |
| id | doaj.art-6a12002216dc45d3a8a5d019f2027bbc |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T20:11:45Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6a12002216dc45d3a8a5d019f2027bbc2022-12-22T04:05:06ZengNature PortfolioScientific Reports2045-23222022-08-0112111510.1038/s41598-022-19172-xAberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expressionSuhail Ahmed0Sathishkumar Kurusamy1Ezra Leander Santhosh David2Kinza Khan3Krithika Kalyanakrishnan4Miebaka Ian-Gobo5Teja Manidhar Kola6Robert N. Wilkinson7Vinodh Kannappan8Weiguang Wang9Manuel J. Gómez10Juan Miguel Redondo11James Cotton12Angel L. Armesilla13Cardiovascular Molecular Pharmacology Laboratory, Research Institute in Healthcare Science, School of Pharmacy, Faculty of Science and Engineering, University of WolverhamptonCardiovascular Molecular Pharmacology Laboratory, Research Institute in Healthcare Science, School of Pharmacy, Faculty of Science and Engineering, University of WolverhamptonCardiovascular Molecular Pharmacology Laboratory, Research Institute in Healthcare Science, School of Pharmacy, Faculty of Science and Engineering, University of WolverhamptonCardiovascular Molecular Pharmacology Laboratory, Research Institute in Healthcare Science, School of Pharmacy, Faculty of Science and Engineering, University of WolverhamptonCardiovascular Molecular Pharmacology Laboratory, Research Institute in Healthcare Science, School of Pharmacy, Faculty of Science and Engineering, University of WolverhamptonCardiovascular Molecular Pharmacology Laboratory, Research Institute in Healthcare Science, School of Pharmacy, Faculty of Science and Engineering, University of WolverhamptonCardiovascular Molecular Pharmacology Laboratory, Research Institute in Healthcare Science, School of Pharmacy, Faculty of Science and Engineering, University of WolverhamptonSchool of Life Sciences, Medical School, Queens Medical Centre, University of NottinghamExperimental Cancer Therapeutics Group, Research Institute in Healthcare Science, Faculty of Science and Engineering, University of WolverhamptonExperimental Cancer Therapeutics Group, Research Institute in Healthcare Science, Faculty of Science and Engineering, University of WolverhamptonUnidad de Bioinformática, Centro Nacional de Investigaciones CardiovascularesGene Regulation in Cardiovascular Remodelling and Inflammation Group, Centro Nacional de Investigaciones CardiovascularesCardiovascular Molecular Pharmacology Laboratory, Research Institute in Healthcare Science, School of Pharmacy, Faculty of Science and Engineering, University of WolverhamptonCardiovascular Molecular Pharmacology Laboratory, Research Institute in Healthcare Science, School of Pharmacy, Faculty of Science and Engineering, University of WolverhamptonAbstract Angiogenesis is a multi-factorial physiological process deregulated in human diseases characterised by excessive or insufficient blood vessel formation. Emerging evidence highlights a novel role for microRNAs as regulators of angiogenesis. Previous studies addressing the effect of miR-133a expression in endothelial cells during blood vessel formation have reported conflicting results. Here, we have assessed the specific effect of mature miR-133a strands in angiogenesis and the expression of endothelial angiogenic genes. Transfection of miR-133a-3p or -5p mimics in primary human endothelial cells significantly inhibited proliferation, migration, and tubular morphogenesis of transfected cells. Screening of gene arrays related to angiogenic processes, and further validation by TaqMan qPCR, revealed that aberrant expression of miR-133a-3p led to a decrease in the expression of genes encoding pro-angiogenic molecules, whilst increasing those with anti-angiogenic functions. Ingenuity Pathway Analysis of a collection of genes differentially expressed in cells harbouring miR-133a-3p, predicted decreased cellular functions related to vasculature branching and cell cycle progression, underlining the inhibitory role of miR-133a-3p in angiogenic cellular processes. Our results suggest that controlled delivery of miR-133a-3p mimics, or antagomirs in diseased endothelial cells, might open new therapeutic interventions to treat patients suffering from cardiovascular pathologies that occur with excessive or insufficient angiogenesis.https://doi.org/10.1038/s41598-022-19172-x |
| spellingShingle | Suhail Ahmed Sathishkumar Kurusamy Ezra Leander Santhosh David Kinza Khan Krithika Kalyanakrishnan Miebaka Ian-Gobo Teja Manidhar Kola Robert N. Wilkinson Vinodh Kannappan Weiguang Wang Manuel J. Gómez Juan Miguel Redondo James Cotton Angel L. Armesilla Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression Scientific Reports |
| title | Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression |
| title_full | Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression |
| title_fullStr | Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression |
| title_full_unstemmed | Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression |
| title_short | Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression |
| title_sort | aberrant expression of mir 133a in endothelial cells inhibits angiogenesis by reducing pro angiogenic but increasing anti angiogenic gene expression |
| url | https://doi.org/10.1038/s41598-022-19172-x |
| work_keys_str_mv | AT suhailahmed aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT sathishkumarkurusamy aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT ezraleandersanthoshdavid aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT kinzakhan aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT krithikakalyanakrishnan aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT miebakaiangobo aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT tejamanidharkola aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT robertnwilkinson aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT vinodhkannappan aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT weiguangwang aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT manueljgomez aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT juanmiguelredondo aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT jamescotton aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression AT angellarmesilla aberrantexpressionofmir133ainendothelialcellsinhibitsangiogenesisbyreducingproangiogenicbutincreasingantiangiogenicgeneexpression |