Prospective study on circulating MicroRNAs and risk of myocardial infarction.
OBJECTIVE
This study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005) in the Bruneck cohort and determine their cellular origin.


BACKGROUND
Circulating miRNAs are emerging as potential biomarkers. We previously identified an miRNA signature for type 2 diabetes in the general population.


METHODS
A total of 19 candidate miRNAs were quantified by real-time polymerase chain reactions in 820 participants.


RESULTS
In multivariable Cox regression analysis, 3 miRNAs were consistently and significantly related to incident myocardial infarction: miR-126 showed a positive association (multivariable hazard ratio: 2.69 [95% confidence interval: 1.45 to 5.01], p = 0.002), whereas miR-223 and miR-197 were inversely associated with disease risk (multivariable hazard ratio: 0.47 [95% confidence interval: 0.29 to 0.75], p = 0.002, and 0.56 [95% confidence interval: 0.32 to 0.96], p = 0.036). To determine their cellular origin, healthy volunteers underwent limb ischemia-reperfusion generated by thigh cuff inflation, and plasma miRNA changes were analyzed at baseline, 10 min, 1 h, 5 h, 2 days, and 7 days. Computational analysis using the temporal clustering by affinity propagation algorithm identified 6 distinct miRNA clusters. One cluster included all miRNAs associated with the risk of future myocardial infarction. It was characterized by early (1 h) and sustained activation (7 days) post-ischemia-reperfusion injury and consisted of miRNAs predominantly expressed in platelets.


CONCLUSIONS
In subjects with subsequent myocardial infarction, differential co-expression patterns of circulating miRNAs occur around endothelium-enriched miR-126, with platelets being a major contributor to this miRNA signature.
King's British Heart Foundation Centre, King's College London, United Kingdom.
Anna
A
Zampetaki
Peter
P
Willeit
Lindsey
L
Tilling
Ignat
I
Drozdov
Marianna
M
Prokopi
Jean-Marie
JM
Renard
Agnes
A
Mayr
Siegfried
S
Weger
Georg
G
Schett
Ajay
A
Shah
Chantal M
CM
Boulanger
Johann
J
Willeit
Philip J
PJ
Chowienczyk
Stefan
S
Kiechl
Manuel
M
Mayr
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000235:genetics*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012016:Reference Values; D015427:Reperfusion Injury / Q000097:blood / Q000235:genetics; D018570:Risk Assessment; D013848:Thigh / Q000098:blood supply
D015415:Biomarkers; D035683:MicroRNAs; C527111:MIRN126 microRNA, human; C546085:MIRN197 microRNA, human; C524940:MIRN21 microRNA, human; C525067:MIR223, human; C543845:MIRN24 microRNA, human