Association of Myocardial Changes and Gene Expression of the NFATC1 and NFATC4—Calcineurin Signaling Pathway in Children with Bicuspid Aortic Valve

Abstract

Background: The role of NFATC gene expression in bicuspid aortic valve (BAV) progression is not fully understood. The aim of this study is to determine the significance of NFATC1 and NFATC4 gene expression for myocardial changes in children with BAV. Methods: In 47 children with BAV, the standard Doppler echocardiographic characteristics were detected, and the expression of the NFATC1 and NFATC4 genes was studied. Results: Posterior wall thickness in diastole (PWTd) and aortic valve peak pressure gradient (AoPPG) in BAV patients were significantly higher compared to healthy controls (PWTd median (min–max), 9 (7–10) mm vs. 7 (6–8) mm; and AoPPG median (min–max), 7.79 (2.98–15.09) mm Hg vs. 2.94 (2.42–3.72) mm Hg). The expression of the NFATC1 gene in BAV children was significantly higher compared to NFATC4 (NFATC1 median (min–max); 70.88 (8.79–106.51) e.u. vs. 7.72 (1.74–22.67) e.u., respectively p < 0.05). A significant correlation of NFATC1 expression with Ao found (R = +0.53, p < 0.05). In BAV patients with PWTd > 8 mm and Ao > 21 mm the NFATC1 expression was significantly higher compared to those with PWTd ≤ 8 mm and Ao ≤ 21 mm (NFATC1 median (min–max); 45.49 (5.01–101.52) e.u. vs. 15.53 (2.36–44.40) e.u., p < 0.05 and 81.11 (20.27–101.10) e.u. mm vs. 12.16 (2.40–45.49) e.u., p < 0.05, respectively). Conclusion: In children with BAV the high expression of the NFATC1 calcineurin signaling pathway gene is associated with elevated PWTd and Ao.

Combined Pharmacological Modulation of Translational and Transcriptional Activity Signaling Pathways as a Promising Therapeutic Approach in Children with Myocardial Changes

“…Expression of transcription-activating genes plays a critical role in the myocardium, not only in cardiac hypertrophy but also in intrauterine cardiac differentiation and valve formation [4,5]. Consistent with this, our previous studies have shown that children with bicuspid aortic valve (BAV) overexpress a nuclear factor of the activated T-cells 1 (NFATC1) gene, the key transcriptional activator, which correlates with the left ventricular hypertrophy [6]. On the other hand, many substances that may be able to inhibit cardiac hypertrophy by this mechanism are currently in various stages of clinical trials.…”

Combined Pharmacological Modulation of Translational and Transcriptional Activity Signaling Pathways as a Promising Therapeutic Approach in Children With Myocardial Changes

“…[4,5] Consistent with this, our previous studies have shown that children with bicuspid aortic valve (BAV) overexpress of the nuclear factor of activated T-cells 1 (NFATC1) gene, the key transcriptional activator, depending on the degree of left ventricular hypertrophy. [6,7]. On the other hand, a number of substances that may be able to inhibit cardiac hypertrophy by this mechanism are currently in various stages of clinical trials.…”