Relationship Between the Temporal Profile of Plasma microRNA and Left Ventricular Remodeling in Patients After Myocardial Infarction

Abstract

Background— microRNAs (miRs) are small noncoding RNAs that recognize and bind to mRNAs and inhibit protein translation or degrade mRNA. Studies in animal models have suggested that miRs play a translational or posttranslational regulatory role in myocardial growth, fibrosis, viability, and remodeling. However, whether specific temporal changes in miRs occur in patients during the left ventricular (LV) remodeling process that follows a myocardial infarction (post-MI) remains unknown. The current pilot study tested the hypotheses that plasma miRs could be reliably measured in post-MI patients and that there is a relationship between temporal changes in specific miRs and post-MI LV structural remodeling. Methods and Results— LV end-diastolic volume (echocardiography) and plasma miR were measured in age-matched referent controls (CTLs, n=12) and post-MI patients (n=12) from day 2 through day 90 post-MI. Selected miRs (miR-1, miR-21, miR-29a, miR-133a, and miR-208) were measured using quantitative reverse transcription–polymerase chain reaction and normalized for endogenous small nuclear RNA U6. After MI, LV end-diastolic volume increased progressively compared with CTL; this was accompanied by time-dependent changes in specific miRs. For example, miR-21 initially decreased 2 days post-MI (0.3±0.1-fold versus CTL; P <0.05), increased 5 days post-MI (2±1-fold versus CTL; P <0.05), and returned to CTL values at later post-MI time points. In contrast, miR-29a increased 5 days post-MI (4±1-fold versus CTL; P <0.05) and then decreased to CTL at later time points. miR-208 increased 5 days post-MI (3±1-fold versus CTL; P <0.05) and remained elevated up to 90 days post-MI. Conclusions— A time-dependent change in miRs occurred in post-MI patients, including an early and robust increase in miRs that has affected myocardial growth, fibrosis, and viability. Thus, serially profiling miRs in the plasma of post-MI patients may hold both mechanistic and prognostic significance.