Abstract 3472: Relationship Between the Temporal Profile of Plasma microRNA and Left Ventricular Remodeling in Patients Following Myocardial Infarction
Background: MicroRNAs (miRNAs) are noncoding RNAs that bind to target mRNAs and reduce their expression through translational repression or mRNA degradation. Measurements made in myocardial tissue have suggested that miRNAs play a regulatory role in myocardial growth, fibrosis, and remodeling. However, whether specific temporal changes in miRNAs occur in patients during the LV remodeling process that follows a myocardial infarction (post-MI) remains unknown. Our goals were:
develop a sensitive, reliable method to serially profile miRNAs in plasma of post-MI patients;
examine the relationship between specific miRNAs and post-MI LV structural remodeling.
Methods and Results: LV end-diastolic volume (EDV, echocardiography) and plasma miRNA were measured in age matched normal (NML n=6) and post-MI patients (n=12) from day 2 through day 90 post-MI. All MI patients received standard therapy. Plasma RNA (100μL) was isolated and miRNA reverse transcription for stem loop primers corresponding to specific miRNAs (miR-1, -21, -29a, 125b, 133a, 208) performed. Resultant cDNA was subjected to pre-amplification (10 cycles) and corresponding miRNA real-time primers. RT-PCR was performed and data normalized for endogenous snRNA U6. This approach provided high sensitivity, linearity and reproducibility. Following MI, LVEDV increased progressively compared to NML; this was accompanied by time dependent changes in specific miRNAs (TABLE⇓). For example, miR-21 initially fell 2 days post-MI, then increased 2-fold over NML 5 days post-MI, and returned to NML 90 days post-MI. In contrast, miR133a and miR-208 increased 5 days post-MI and remained elevated 90 days post-MI.
Conclusions: A unique temporal pattern of miRNAs occurred in post-MI patients including changes in miRNAs previously shown to regulate myocardial growth, fibrosis and remodeling. Thus, serially profiling miRNAs in the plasma of post-MI patients may hold both mechanistic and prognostic significance.