Circulating miRNAs as potential biomarkers of microvascular cardiac allograft vasculopathy after heart transplantation
I A Just, F Schoenrath, L Roehrich, P Stawowy, V Falk, T ZellerAbstract
Background
Cardiac allograft vasculopathy (CAV) remains a leading cause of late morbidity and mortality after heart transplantation (HTX). Early, exclusively microvascular (microvasulopathy, MVP) forms are clinically relevant but poorly detected by routine follow-up. Molecular biomarkers may provide complementary pathophysiological information and improve risk stratification beyond current diagnostic approaches.
Objective
To explore circulating microRNAs associated with MVP as potential non-invasive biomarkers.
Methods
In a prospectively phenotyped HTX cohort, serum samples from 15 recipients were analyzed (mean age 48.6 ± 17.6 years; 27.3% female; median time since HTX 6.8 [3.5; 16.1] years). MVP (n=6) and control (n=9) group were defined by invasive coronary microcirculatory assessment using the index of microcirculatory resistance (IMR; MVP ≥ 23, controls < 23). Circulating miRNAs were quantified using the miRCURY LNA RT Kit and Human Panel I (Qiagen). Data were normalized by the global mean. Differential expression was assessed using unpaired t-tests with Shapiro–Wilk testing for normality and Wilcoxon tests as sensitivity analyses. Multiple testing was addressed using Benjamini–Hochberg false discovery rate (FDR) correction.
Results
Of 171 consistently detected miRNAs, 14 showed nominal differential expression between MVP and controls (p < 0.05), but none remained significant after FDR correction in the full panel analysis. To address limited statistical power, a secondary dimension-reduced analysis focusing on the five strongest candidates (miR-136-3p, miR-125a-5p, miR-99a-5p, miR-10b-5p, miR-335-3p) was performed. Within this restricted set, all five miRNAs remained significant after FDR correction.
Conclusions
This pilot study demonstrates the feasibility of serum miRNA profiling in HTX recipients and identifies candidate miRNAs potentially associated with MVP. Limited sample size likely constrained statistical power in the full panel analysis. These exploratory findings support further validation in adequately powered cohorts to assess the role of miRNA signatures in non-invasive post-transplant surveillance.For image description, please refer to the figure legend and surrounding text.