Abstract 12800: MicroRNA-1 and MicroRNA-133a are Useful as Early Diagnostic Biomarkers in Patients with Acute Coronary Syndrome
Background: The discovery of new biomarkers is important in the cardiovascular field, since they facilitate an early diagnosis and guide the prognosis. microRNAs (miRNAs or miRs) are small non-coding RNAs that modulate messenger RNA stability and translation. Recently, some reports have indicated that exosomes, which are membrane-coated vesicles, contain miRNAs, and these exist in blood. However, the significance of circulating miRNAs in patients with cardiovascular disease has not been elucidated.
Methods and Results: MiR−1, −133a, −133b, −206, −208a, −208b, and −499 are known as muscle-specific miRNAs. To evaluate the expression levels of muscle-specific miRNAs in the heart, we performed miRNA array analysis of RNA prepared from normal mouse hearts (the four specimens were mixed). miR−1, −133a, and −208a were abundantly expressed in the heart. Thus, we evaluated the expression levels of miR−1, −133a, and −208a in the serum of patients with cardiovascular disease. Fifty-five patients were analyzed by miRNA qRT-PCR assay. miR-1 and −133a expression levels were detectable in 42.9 and 80.0% of patients, respectively. On the other hand, the miR−208a expression level was detectable in few patients (5.7%). The patients were classified according to their disease. miR−1 and −133a expression levels were significantly increased in acute coronary syndrome patients (n=22) compared with other patients (miR−1: 1.7±0.2 vs. 90.2±58.8, p<0.05; miR−133a: 4.8±1.7 vs. 421.7±152.4, p<0.0001, respectively). To examine whether miR−1 and −133a in serum are useful as early diagnostic biomarkers, we evaluated the time-course of miR−1 and −133a expression in the serum of a mouse myocardial infarction model. The expression levels of miR−1 and −133a were significantly increased in serum at 1 hour after coronary ligation. Furthermore, we carried out in situ hybridization in a mouse model of myocardial infarction. A strong miR−133a signal was identified in the non-infarcted region, but it was decreased in the border zone. In the infarcted region, the signal was very weak. The results suggest that these miRNAs are released from the infarcted myocardium.
Conclusions: MicroRNA−1 and −133a are useful as early diagnostic biomarkers in patients with acute coronary syndrome.
- © 2010 by American Heart Association, Inc.