Micro-RNA 92a as a therapeutic target for cardiac microvascular dysfunction in diabetes
Microvascular dysfunction is a pathological hallmark of diabetes, and is central to the ethology of diabetes-associated cardiac events. Herein, previous studies have highlighted the role of the vasoactive micro-RNA 92a (miR-92a) in small, as well as large, animal models. In this study, we explore th...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2022
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| In: |
Biomedicines
Year: 2022, Volume: 10, Issue: 1, Pages: 1-16 |
| ISSN: | 2227-9059 |
| DOI: | 10.3390/biomedicines10010058 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/biomedicines10010058 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2227-9059/10/1/58 
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| Author Notes: | Mostafa Samak, Diana Kaltenborn, Andreas Kues, Ferdinand Le Noble, Rabea Hinkel and Giulia Germena |
| Summary: | Microvascular dysfunction is a pathological hallmark of diabetes, and is central to the ethology of diabetes-associated cardiac events. Herein, previous studies have highlighted the role of the vasoactive micro-RNA 92a (miR-92a) in small, as well as large, animal models. In this study, we explore the effects of miR-92a on mouse and human cardiac microvascular endothelial cells (MCMEC, HCMEC), and its underlying molecular mechanisms. Diabetic HCMEC displayed impaired angiogenesis and a pronounced inflammatory phenotype. Quantitative PCR (qPCR) showed an upregulation of miR-92a in primary diabetic HCMEC. Downregulation of miR-92a by antagomir transfection in diabetic HCMEC rescued angiogenesis and ameliorated diabetic endothelial bed inflammation. Furthermore, additional analysis of potential in silico-identified miR-92a targets in diabetic HCMEC revealed the miR-92a dependent downregulation of an essential metalloprotease, ADAM10. Accordingly, downregulation of ADAM10 impaired angiogenesis and wound healing in MCMEC. In myocardial tissue slices from diabetic pigs, ADAM10 dysregulation in micro- and macro-vasculature could be shown. Altogether, our data demonstrate the role of miR-92a in cardiac microvascular dysfunction and inflammation in diabetes. Moreover, we describe for the first time the metalloprotease ADAM10 as a novel miR-92a target, mediating its anti-angiogenic effect. |
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| Item Description: | Gesehen am 15.11.2022 Published: 28 December 2021 |
| Physical Description: | Online Resource |
| ISSN: | 2227-9059 |
| DOI: | 10.3390/biomedicines10010058 |