MicroRNA expressions in right ventricular outflow tract myocardium correlate with pulmonary valve size in patients with tetralogy of Fallot

OBJECTIVES: Although microRNAs are critical regulators of mRNA, and dysregulation may contribute to the development of tetralogy of Fallot (TOF), the precise mechanism remains unknown. We aimed to compare microRNA expressions in the right ventricular outflow tract (RVOT) myocardium between patients with different surgical repair types to evaluate the impact on disease severity. METHODS: RVOT myocardial tissues were collected from patients at definitive surgery for TOF. Patients who underwent transannular patch or infundibular patch repair were classified as the infundibular repair group, and others as the non-infundibular repair group. MicroRNA expression levels in these tissues were measured quantitatively using microarray. MicroRNA expression levels were compared between the two groups, and the correlations between microRNA expression levels and pulmonary valve diameter indexed to body surface area were analyzed. RESULTS: 948 microRNAs were identified out of 2,632 available sequences from 21 patients. The expression levels of 48 microRNAs differed between the infundibular repair and non-infundibular repair groups (p < 0.05 before false discovery rate correction). Forty-four microRNAs were upregulated, and four were downregulated in the non-infundibular repair group compared to the infundibular repair group. Furthermore, among these 48 microRNAs, 11 microRNAs demonstrated significant correlations with pulmonary valve size in both Pearson's and Spearman's analyses. Four of these microRNAs showed strong correlation coefficients greater than 0.50 across both analyses. CONCLUSIONS: Differential expression of several microRNAs in RVOT myocardium was significantly associated with pulmonary valve size. These identified microRNAs may provide molecular pathways for future studies investigating the mechanisms underlying RVOT development.