Circulating microRNAs in patients with coronary artery disease.
BACKGROUND
MicroRNAs are small RNAs that control gene expression. Besides their cell intrinsic function, recent studies reported that microRNAs are released by cultured cells and can be detected in the blood.


OBJECTIVE
To address the regulation of circulating microRNAs in patients with stable coronary artery disease.


RESULTS
To determine the regulation of microRNAs, we performed a microRNA profile using RNA isolated from n=8 healthy volunteers and n=8 patients with stable coronary artery disease that received state-of-the-art pharmacological treatment. Interestingly, most of the highly expressed microRNAs that were lower in the blood of patients with coronary artery disease are known to be expressed in endothelial cells (eg, miR-126 and members of the miR-17 approximately 92 cluster). To prospectively confirm these data, we detected selected microRNAs in plasma of 36 patients with coronary artery disease and 17 healthy volunteers by quantitative PCR. Consistent with the data obtained by the profile, circulating levels of miR-126, miR-17, miR-92a, and the inflammation-associated miR-155 were significantly reduced in patients with coronary artery disease compared with healthy controls. Likewise, the smooth muscle-enriched miR-145 was significantly reduced. In contrast, cardiac muscle-enriched microRNAs (miR-133a, miR-208a) tend to be higher in patients with coronary artery disease. These results were validated in a second cohort of 31 patients with documented coronary artery disease and 14 controls.


CONCLUSIONS
Circulating levels of vascular and inflammation-associated microRNAs are significantly downregulated in patients with coronary artery disease.
Fichtlscherer
Stephan
S
Institute for Cardiovascular Regeneration, Goethe University Frankfurt, Theodor Stern Kai 7, Frankfurt, Germany.
De Rosa
Salvatore
S
Fox
Henrik
H
Schwietz
Thomas
T
Fischer
Ariane
A
Liebetrau
Christoph
C
Weber
Michael
M
Hamm
Christian W
CW
Röxe
Tino
T
Müller-Ardogan
Marga
M
Bonauer
Angelika
A
Zeiher
Andreas M
AM
Dimmeler
Stefanie
S
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D005858:Germany; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011859:Radiography; D015203:Reproducibility of Results; D015854:Up-Regulation
D005819:Genetic Markers; C527111:MIRN126 microRNA, human; C548234:MIRN133 microRNA, human; C541010:MIRN145 microRNA, human; C524942:MIRN155 microRNA, human; C524941:MIRN17 microRNA, human; C550906:MIRN208 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs