14q32 Noncoding RNAs in vascular remodelling

Goossens, E.A.C. (2020)

Doctoral Thesis

14q32 microRNAs are known to play a role in various forms of vascular remodelling. This thesis elucidated that snoRNAs of the 14q32 locus are also involved in vascular remodelling processes. The expression of both noncoding RNA types in the human vasculature has been found to be vascular location and vessel type specific and are therefore promising targets for future implementation in clinical practice.
The second part of this thesis focuses on three different types of 14q32 microRNA expression regulation in order to affect various vascular remodelling processes. 14q32 DNA methylation, myostatin and CIRBP were tested for their effect on 14q32 microRNA expression and the (subsequent) effect on vein graft disease and tissue ischemia, restenosis and angiogenesis, respectively. DNA methylation is not correlated with 14q32 microRNA expression, but directly interacts with vascular remodelling process status. Myostatin negatively affects 14q32 microRNA expression in vascular smooth muscle cells, but not in inflammatory cells involved in restenosis. Due to this latter finding, overall restenosis was not inhibited by myostatin. Inhibition of CIRBP inhibited 14q32 microRNA expression post-transcriptionally and therefore increased in vitro angiogenesis. These promising findings provide novel indirect regulators of vascular remodelling processes and future research will elucidate the potential for clinical application.

• Cardiovascular disease
• Vascular remodelling
• Noncoding RNAs
• MicroRNAs
• SnoRNAs
• 14q32 locus
• (Post-)transcriptional regulation
• RNA binding protein
• DNA methylation

• All authors: Goossens, E.A.C.
• Supervisor: Quax, P.H.A.
• Co-supervisor: Nossent, A.Y.
• Committee: Hamming, J.F.; Jukema, J.W.; Goumans, M.J.T.H.; Creemers, E.E.J.M.; Jager, S.C.A. de
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2020-04-09
• ISBN (print): 9789463758352