The peripheral blood mononuclear cell microRNA signature of coronary artery disease.
BACKGROUND
MicroRNAs are being used in the oncology field to characterize tumors and predict the survival of cancer patients. Here, we explored the potential of microRNAs as biomarkers for coronary artery disease (CAD) and acute coronary syndromes.


RESULTS
Using real-time PCR-based profiling, we determined the microRNA signature of peripheral blood mononuclear cells (PBMCs) from stable and unstable CAD patients and unaffected controls. 129 of 157 microRNAs measured were expressed by PBMCs and low variability between separate PBMC pools was observed. The presence of CAD in general coincided with a marked 5-fold increase (P<0.001) in the relative expression level of miR-135a, while the expression of miR-147 was 4-fold decreased (P<0.05) in PBMCs from CAD patients as compared to controls, resulting in a 19-fold higher miR-135a/miR-147 ratio (P<0.001) in CAD. MicroRNA/target gene/biological function linkage analysis suggested that the change in PBMC microRNA signature in CAD patients is probably associated with a change in intracellular cadherin/Wnt signaling. Interestingly, unstable angina pectoris patients could be discriminated from stable patients based upon their relatively high expression level of a cluster of three microRNAs including miR-134, miR-198, and miR-370, suggesting that the microRNA signatures can be used to identify patients at risk for acute coronary syndromes.


CONCLUSIONS
The present study is the first to show that microRNA signatures can possibly be utilized to identify patients exhibiting atherosclerotic CAD in general and those at risk for acute coronary syndromes. Our findings highlight the importance of microRNAs signatures as novel tool to predict clinical disease outcomes.
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Einsteinweg 55, P.O. Box 9502, 2300RA Leiden, The Netherlands. Hoekstra@LACDR.Leidenuniv.nl
Menno
M
Hoekstra
Christian A C
CA
van der Lans
Bente
B
Halvorsen
Lars
L
Gullestad
Johan
J
Kuiper
Pål
P
Aukrust
Theo J C
TJ
van Berkel
Erik A L
EA
Biessen
D000787:Angina Pectoris / Q000175:diagnosis / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis
C544965:MIRN135 microRNA, human; D035683:MicroRNAs