MicroRNA-126 measurements in right ventricular endomyocardial biopsies of heart transplant recipients with and without cardiac allograft vasculopathy

W.A. Heggermont, L. Delrue, K. Dierickx, J. Bartunek, M. Vanderheyden

Thursday 15 march 2018

12:40 - 12:50h at Van Weelde Zaal

Categories: Basic / translational research, Session (parallel)

Parallel session: Parallel session 2: Basic / translational research

Background

Endothelium-enriched microRNAs (miRs) appear to be involved in the development of CAV. Recently, serum miR-126-3p and -5p, known endothelial microRNAs with a crucial function in angiogenesis and re-endothelialization, seem to provide additional evidence for cardiac allograft vasculopathy in addition to clinical predictors. However, their myocardial expression in and relationship with CAV is unknown. Our study aim was to investigate the expression of endomyocardial microRNA-126-3p and microRNA-126-5p levels in heart transplant recipients and their relationship with allograft vasculopathy.

Methods

We studied 39 heart transplant recipients, 21 with proven allograft vasculopathy (CAV+) and 18 without allograft vasculopathy (CAV-) with serial coronary angiograms. Eight patients with end-stage native coronary artery disease were added to the study in order to investigate disease specificity. The mRNA levels of miR-126-3p and miR-126-5p, and few of their targets, were determined by qRT-PCR in right ventricular endomyocardial biopsies obtained at baseline and during routine follow-up.

Results

No significant difference in myocardial microRNA-126-3p or -5p levels was noted between CAV+ and CAV- patients at baseline. At baseline, the ratio in miR-126-3p/-5p levels was similar in both groups. In contrast, the miR-126-3p/-5p levels were significantly lower in the CAV+ group compared to the CAV- group at follow-up; a difference primarily driven by lower miR-126a-3p levels. This was in contrast to native CAD patients in which miR-126-3p and -5p levels and the ratio were significantly higher.

Conclusions

Our data provide evidence for a distinct microRNA signature in patients with allograft vasculopathy. In contrast to CAD patients, the lower ratio of miR-126-3p/-5p clearly coincides with the development of cardiac allograft vasculopathy. Further studies are warranted to determine if serial measurement of myocardial microRNA-126 products could help in risk assessment and early detection of CAV.