Transcoronary concentration gradients of circulating miRNAs in heart failure

Circulating levels of microRNA (miRs) are emergent promising biomarkers for cardiovascular disease. Altered expression of miRs has been related to heart failure (HF) and cardiac remodeling. To identify the potential source for miRs released into the circulation, we measured the concentration gradients across the coronary circulation to assess their usefulness to diagnose HF of different etiologies. Circulating miRs were measured by TaqMan polymerase chain reaction in EDTA-plasma simultaneously obtained from the aorta (Ao) and the coronary venous sinus (CVS) in patients with non-ischemic HF (NICM-HF, n=23), or ischemic HF (ICM-HF, n=23), as well as from control subjects with no HF (n=11). We found differential modulation of circulating levels of the miRs 423, 34a, 21-3p and 126 across the etiology HF groups. Interestingly, we found a positive transcoronary gradient for the miR-423 (p<0.001) and the miR-34a (p<0.001), only in the ICM-HF group. On the contrary, a positive transcoronary gradient was found for the miR-21-3p (p<0.001) only in the NICM-HF group. Finally, despite the dramatic downregulation observed for the miR-126 in HF patients (p<0.001) compared to controls, no significant variations were observed in its transcoronary gradient. The present findings suggest that circulating levels of miRs are differentially expressed in patients with HF of different etiologies. The presence of a transcoronary concentration gradient suggests a selective release of miR by the failing heart into the coronary circulation. The presence of etiology-specific transcoronary concentration gradient in HF patients might provide important information to better understand their role in HF, and suggests they could be useful biomarkers to distinguish HF of different etiologies.