Abstract 13152: The Human Myocardial Interstitium Contains a Specific Portfolio of microRNAs which are Dynamically Regulated Following Ischemia-Reperfusion
Background: MicroRNAs (miRs) regulate post-transcriptional events relevant to myocardial growth, viability and matrix remodeling (ie miR−1, −21, −29a, −133a. −486, −760). However, direct demonstration that miRs are released in a quantifiable manner within human myocardial interstitial fluid (INTf) and dynamically changed following ischemia-reperfusion (I/R) remained defined.
Methods and Results: Using novel microdialysis methods and high-sensitivity extraction, INTf was collected from the mid-myocardium of the LV free wall in patients (n=10, 63±3 yrs, male) undergoing elective coronary revascularization for the continuous collection of INTf prior to cardioplegic/myocardial arrest and cardiopulmonary bypass (Baseline) and following cross-clamp release and reperfusion (POST-I/R), with plasma collected at identical time points. Absolute miR content was determined by real-time PCR with a coefficient of variation of less than 10% where a consistent yield of the constitutive miR-RNU6B was obtained from both INTf and plasma samples (31.9±0.4, 29.9±1.2 Ct, respectively). A robust Baseline miR concentration was detected in the INTf as well as plasma (Table). Higher levels of certain miRs (miR−1, −133a, −760) which regulate growth and signaling, were in the INTf-indicative of myocardial compartmentalization. Dynamic changes occurred in both INTf and plasma following I/R (Table), where selective miRs differentially changed within the INTf such as miR−1 and −760.
Conclusions: These unique findings demonstrated a robust expression of miRs which regulate myocyte and matrix remodeling within the human myocardial interstitium and dynamically change with I/R. In light of the fact that miRs form an important control point in transcriptional regulation, this study provides the first clinical evidence that miRs likely form a novel extracellular signaling/regulatory pathway within the intact human myocardium.
- © 2010 by American Heart Association, Inc.