Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans.
OBJECTIVE
microRNA (miRNA) is reported to be present in the blood of humans and has been increasingly suggested as a biomarker for diseases. We aim to determine the potential of cardiac-specific miRNAs in circulation to serve as biomarkers for acute myocardial infarction (AMI).


RESULTS
By verifying their tissue expression patterns with real-time polymerase chain reaction (PCR) analysis, muscle-enriched miRNAs (miR-1, miR-133a, and miR-499) and cardiac-specific miR-208a were selected as candidates for this study. With miRNA microarray and real-time PCR analyses, miR-1, miR-133a, and miR-499 were present with very low abundance, and miR-208a was absent in the plasma from healthy people. In the AMI rats, the plasma levels of these miRNAs were significantly increased. Especially, miR-208a in plasma was undetected at 0 h, but was significantly increased to a detectable level as early as 1 h after coronary artery occlusion. Further evaluation of the miRNA levels in plasma from AMI patients (n = 33) demonstrated that all four miRNA levels were substantially higher than those from healthy people (n = 30, P < 0.01), patients with non-AMI coronary heart disease (n = 16, P < 0.01), or patients with other cardiovascular diseases (n = 17, P < 0.01). Notably, miR-208a remained undetectable in non-AMI patients, but was easily detected in 90.9% AMI patients and in 100% AMI patients within 4 h of the onset of symptoms. By receiver operating characteristic curve analysis, among the four miRNAs investigated, miR-208a revealed the higher sensitivity and specificity for diagnosing AMI.


CONCLUSIONS
Elevated cardiac-specific miR-208a in plasma may be a novel biomarker for early detection of myocardial injury in humans.
Department of Cardiology, Changhai Hospital, 168 Changhai Road, Shanghai 200433, People's Republic of China.
Guo-Kun
GK
Wang
Jia-Qi
JQ
Zhu
Jun-Tao
JT
Zhang
Qing
Q
Li
Yue
Y
Li
Jia
J
He
Yong-Wen
YW
Qin
Qing
Q
Jing
D000818:Animals; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D003331:Coronary Vessels; D004195:Disease Models, Animal; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008026:Ligation; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009203:Myocardial Infarction / Q000175:diagnosis*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D035683:MicroRNAs