Micro-RNA 92a as a Therapeutic Target for Cardiac Microvascular Dysfunction in Diabetes
| Autor: | Mostafa Samak, Diana Kaltenborn, Andreas Kues, Ferdinand Le Noble, Rabea Hinkel, Giulia Germena |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Life sciences
biology 0303 health sciences diabetes QH301-705.5 Medicine (miscellaneous) mir-92a 030204 cardiovascular system & hematology General Biochemistry Genetics and Molecular Biology Article 3. Good health 03 medical and health sciences angiogenesis 0302 clinical medicine endothelial function inflammation ddc:570 Biology (General) 030304 developmental biology |
| Zdroj: | Biomedicines, Vol 10, Iss 58, p 58 (2022) Biomedicines, 10 (1), Art. Nr.: 58 Biomedicines; Volume 10; Issue 1; Pages: 58 Biomedicines |
| ISSN: | 2227-9059 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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