Micro-RNA 92a as a therapeutic target for cardiac microvascular dysfunction in diabetes

• Verfasst von: Samak, Mostafa [VerfasserIn]
• Verfasst von: Kaltenborn, Diana [VerfasserIn]
• Verfasst von: Kues, Andreas [VerfasserIn]
• Verfasst von: Le Noble, Ferdinand [VerfasserIn]
• Verfasst von: Hinkel, Rabea [VerfasserIn]
• Verfasst von: Germena, Giulia [VerfasserIn]
• Titel: Micro-RNA 92a as a therapeutic target for cardiac microvascular dysfunction in diabetes
• Verf.angabe: Mostafa Samak, Diana Kaltenborn, Andreas Kues, Ferdinand Le Noble, Rabea Hinkel and Giulia Germena
• Jahr: 2022
• Umfang: 16 S.
• Fussnoten: Gesehen am 15.11.2022 ; Published: 28 December 2021
• Titel Quelle: Enthalten in: Biomedicines
• Ort Quelle: Basel : MDPI, 2013
• Jahr Quelle: 2022
• Band/Heft Quelle: 10(2022), 1, Artikel-ID 58, Seite 1-16
• ISSN Quelle: 2227-9059
• DOI: doi:10.3390/biomedicines10010058
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: angiogenesis
• Sach-SW: diabetes
• Sach-SW: endothelial function
• Sach-SW: inflammation
• Sach-SW: mir-92a
• K10plus-PPN: 1822491444

Abstract

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.