Clinical and Biological Aspects of Cardiovascular microRNA
Summary, in English
The aim of this thesis was (1) to assess the diagnostic and prognostic value of cardiac-enriched miRNAs in the context of coronary artery disease, (2) to screen for differences in miRNA content in platelets from myocardial infarction patients and elucidate a potential paracrine function for platelet miRNA and (3) to investigate the role of miRNAs in regulating endothelial inflammation in response to extracellular ATP/UTP.
In Study I and II, we found that cardiac-enriched miRNAs are increased 100-3000 fold within 12 h following onset of symptoms in patients with myocardial infarction and that the levels of two specific miRNAs, miR-208b and-499-5p, could be used to discriminate MI-patients from non-MI patients and were associated with increased risk of death and development of heart failure. In Study III, we found differentially expressed platelet miRNAs in MI patients compared to healthy controls using RNA-sequencing. Release of miRNAs upon platelet activation, as well as microparticle-dependent transfer of functional platelet-derived miRNA to endothelial cells was also shown in vitro. In Study IV, we showed that the effects of ATP and UTP on cell surface expression of intercellular adhesion molecule 1 (ICAM-1) and leukocyte adhesion is mediated in part by miR-22 in endothelial cells.
In conclusion, the levels of circulating cardiac-enriched miRNA have diagnostic and prognostic value in the context of coronary artery disease, platelet-derived miRNA can act as paracrine mediators in endothelial cells and miR-22 plays an anti-inflammatory role in the endothelium.
Lund University Faculty of Medicine Doctoral Dissertation Series
Cardiology, Lund University
- Cardiac and Cardiovascular Systems
- David Erlinge
- Björn Olde
- Oscar Braun
- ISSN: 1652-8220
- ISBN: 978-91-87449-59-8
20 September 2013
Segerfalksalen BMC Lund
- Niels Heegaard