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Small regulatory RNAs in vascular remodeling and atherosclerosis
Noncoding RNAs (ncRNAs) are RNAs that are not translated into protein. This thesis focuses on two types: microRNAs and small nucleolar RNAs (snoRNAs).
MicroRNAs inhibit the production of proteins and act on multiple proteins simultaneously. In CVD, many different proteins are involved. Changing expression of one microRNA can therefore have a major impact.
Numerous snoRNAs have been associated with diseases, including CVD. The function of half of the human C/D box snoRNAs, however, is unknown.
The first aim of this thesis is to investigate inhibition of microRNA-494-3p in advanced atherosclerosis. The second aim is to elucidate the function of SNORD113-6, a snoRNA that is involved in CVD.
The thesis shows that inhibition of microRNA-494-3p halts plaque progression...Show moreCardiovascular disease (CVD) is a major cause of death worldwide. The underlying cause of most CVD is atherosclerosis. Atherosclerosis is characterized by progressive plaque build-up in the arterial wall.
Noncoding RNAs (ncRNAs) are RNAs that are not translated into protein. This thesis focuses on two types: microRNAs and small nucleolar RNAs (snoRNAs).
MicroRNAs inhibit the production of proteins and act on multiple proteins simultaneously. In CVD, many different proteins are involved. Changing expression of one microRNA can therefore have a major impact.
Numerous snoRNAs have been associated with diseases, including CVD. The function of half of the human C/D box snoRNAs, however, is unknown.
The first aim of this thesis is to investigate inhibition of microRNA-494-3p in advanced atherosclerosis. The second aim is to elucidate the function of SNORD113-6, a snoRNA that is involved in CVD.
The thesis shows that inhibition of microRNA-494-3p halts plaque progression and increases stability of advanced plaques. This reduces the risk of e.g. a myocardial infarction.
Furthermore, SNORD113-6 influences the function of fibroblasts, scar cells, and thus plays a role in maintaining function of our blood vessels.
These insights may open up new therapeutic possibilities in future treatment of CVD.
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- All authors
- Ingen, E. van
- Supervisor
- Quax, P.H.A.
- Co-supervisor
- Nossent, A.Y.
- Committee
- Goumans, M.J.T.H.; Rensen, P.C.N.; Boon, R.A.; Bot, I.
- Qualification
- Doctor (dr.)
- Awarding Institution
- Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
- Date
- 2022-06-09
- ISBN (print)
- 9789464582468
Funding
- Sponsorship
- The research described in this thesis was supported by a grant from the Rembrandt Institute of Cardiovascular Science (2016).