Abstract 16838: Circulating miRNAs Can Predict Cardiac Allograft Vasculopathy in Pediatric Heart Transplant Recipients in a Sex-dependent Manner

Abstract

Introduction: MicroRNAs (miRs) are small noncoding ~22 nucleotide RNAs capable of modulating the expression of many genes. Our hypothesis was that circulating miRs are useful biomarkers of cardiac allograft vasculopathy (CAV) in pediatric heart transplant recipients (PHTR). Methods: An array for 765 miRs was performed using the Applied Biosystems technology normalized by a global normalization method as determined by the Expression Suite Software. Serum was obtained from 132 PHTR at the time of routine surveillance catheterization with coronary evaluation (intravascular ultrasound [IVUS] performed if ≥ 25 kg). Rejection free CAV+ patients were matched by age at transplant and time since transplant to CAV- controls. Statistical analysis was performed using the Wilcoxon test. Results: Samples were analyzed from 32 CAV+ PHTR matched to 17 CAV-controls. There were no significant differences between expression of miRs between CAV+ and CAV- PHTR alone, but differences in expression were found when PHTR were separated by sex. miRs significantly upregulated in females (F) included miRs-636 (F with both IVUS and angiographic CAV; p=0.008), -636 and -523 (F with a maximal intimal thickness [MIT] of ≥ 0.5mm; p=0.008 and 0.01, respectively), and -509 and -636 (F with any diagnosis of CAV; p=0.01 and p=0.01, respectively). miRs significantly upregulated in males (M) included miRs-422a (M with both IVUS and angiographic CAV; p=0.007), -422a and let-7e (M with a MIT of ≥ 0.5mm; p=0.003 and p=0.01, respectively), and -422a (M with any diagnosis of CAV; p=0.002). miR-19a was significantly downregulated in in M with any diagnosis of CAV (p=0.04). Boxplots highlighting differential expression of miRs by sex in CAV are shown in Figure 1. Conclusions: miRs are differentially expressed between PHTR with CAV on the basis of sex. A unique biomarker signature of miRs that are specific to PHTR with CAV would be valuable in the risk stratification of this challenging patient population.