Abstract 3587: Micro RNAs Could Play a Critical Role in Progression of Diastolic Dysfunction in Mildly Symptomatic Patients With Chronic Heart Failure
Objectives: In recent years, left ventricular (LV) diastolic dysfunction has become widely recognized as a new problem because this condition induces diastolic heart failure. LV diastolic dysfunction is also an important prognostic marker in patients with chronic heart failure with systolic dysfunction. However, the molecular mechanisms that underlie diastolic dysfunction remain incompletely understood. MicroRNAs (miRNAs) are recently discovered, posttranscriptional regulators of gene expression. We, therefore, hypothesized that miRNAs might play a role in the pathogenesis of myocardial abnormal relaxation, which is known to result in LV diastolic dysfunction.
Methods: Left ventricular (LV) pressures were measured using a micromanometer-tipped catheter system and LV pressure half-time (T1/2) was calculated as an index of myocardial relaxation in 13 mildly symptomatic patients with idiopathic dilated cardiomyopathy. We also performed genome-wide miRNA expression profiling in each endomyocardial biopsy specimens obtained from these 13 patients.
Results: Eight patients had delayed (T1/2 >38msec) myocardial relaxation (group I) and 5 had normal (T1/2 ≤38msec) myocardial relaxation (group II). LV ejection fraction evaluated by left ventriculography did not differ between groups I and II (29±9 vs. 38±10%, respectively), and plasma BNP levels in group I were higher compared with those in group II (357±503 vs. 91±126 pg/ml, respectively). Out of 650 miRNAs measured, 8 were differentially expressed in group I compared with group II (p<0.01). The expressions of 5 miRNAs were significantly (p<0.01) reduced and the expressions of 3 miRNAs were significantly (p<0.01) increased in group I compared with group II.
Conclusion: We demonstrated that specific miRNAs could play a critical role in the pathogenesis of delayed myocardial relaxation in mildly symptomatic patients with idiopathic dilated cardiomyopathy. These findings call attention to the potential of miRNAs to provide etiologic insights as well as therapeutic targets for progression of diastolic dysfunction in patients with chronic heart failure.