Platelets in patients with premature coronary artery disease exhibit upregulation of miRNA340* and miRNA624*.
BACKGROUND
Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls.


RESULTS
In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts.


CONCLUSIONS
Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective study.
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Brigitte M
BM
Sondermeijer
Annemieke
A
Bakker
Amalia
A
Halliani
Maurice W J
MW
de Ronde
Arnoud A
AA
Marquart
Anke J
AJ
Tijsen
Ties A
TA
Mulders
Maayke G M
MG
Kok
Suzanne
S
Battjes
Steffi
S
Maiwald
Suthesh
S
Sivapalaratnam
Mieke D
MD
Trip
Perry D
PD
Moerland
Joost C M
JC
Meijers
Esther E
EE
Creemers
Sara-Joan
SJ
Pinto-Sietsma
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015203:Reproducibility of Results; D015854:Up-Regulation / Q000235:genetics*
C570046:MIRN340 microRNA, human; C570047:MIRN624 microRNA, human; D035683:MicroRNAs