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Updated: Dec 25, 2025

In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
Variations of circulating miRNA in paediatric patients with Heart Failure supported with Ventricular Assist Device: a
Rosetta Ragusa1,2, Arianna Di Molfetta3, Romina D'Aurizio4
1Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
Insights
Circulating microRNAs (c-miRNAs) in pediatric heart failure (HF) children changed after 30 days of ventricular assist device (VAD) treatment, potentially indicating a pro-thrombotic state. Six c-miRNAs involved in hemostasis were identified.
Area of Science:
- Biochemistry
- Molecular Biology
- Pediatric Cardiology
Background:
- Circulating microRNAs (c-miRNAs) show potential as biomarkers for heart failure (HF) diagnosis and prognosis.
- Limited research exists on c-miRNA profiles in pediatric HF patients, particularly those undergoing ventricular assist device (VAD) implantation.
Purpose of the Study:
- To investigate the c-miRNA profile in children with HF.
- To assess the impact of VAD implantation on c-miRNA levels.
- To validate potential c-miRNA targets in vitro.
Main Methods:
- Serum c-miRNA profiling using Next-Generation Sequencing (NGS) before and after VAD implantation.
- Real-time PCR validation of differentially expressed c-miRNAs at multiple time points post-VAD.
- In vitro miRNA mimic transfection in HepG2 cells to validate miRNA-target interactions.
Main Results:
- Thirteen c-miRNAs showed altered levels 30 days post-VAD compared to pre-VAD levels; six were confirmed by Real-Time PCR.
- Validated c-miRNAs target genes involved in the hemostatic process.
- In vitro studies confirmed hsa-miR-409-3p down-regulates coagulation factors F7 and F2, and all patients experienced thrombotic events.
Conclusions:
- VAD treatment in pediatric HF patients alters the levels of six c-miRNAs regulating hemostatic events within 30 days.
- A decrease in c-miR-409-3p, targeting F7 and F2, may indicate a pro-thrombotic state post-VAD implantation.
- These findings highlight potential c-miRNA biomarkers for monitoring thrombotic risk in pediatric VAD patients.
Abstract:
Circulating miRNAs (c-miRNAs) are promising biomarkers for HF diagnosis and prognosis. There are no studies on HF pediatric patients undergoing VAD-implantation. Aims of this study were: to examine the c-miRNAs profile in HF children; to evaluate the effects of VAD on c-miRNAs levels; to in vitro validate putative c-miRNA targets. c-miRNA profile was determined in serum of HF children by NGS before and one month after VAD-implant. The c-miRNA differentially expressed were analyzed by real time-PCR, before and at 4 hrs,1,3,7,14,30 days after VAD-implant. A miRNA mimic transfection study in HepG2 cells was performed to validate putative miRNA targets selected through miRWalk database. Thirteen c-miRNAs were modified at 30 days after VAD-implant compared to pre-VAD at NSG, and, among them, six c-miRNAs were confirmed by Real-TimePCR. Putative targets of the validated c-miRNAs are involved in the hemostatic process. The in vitro study confirmed a down-regulatory effect of hsa-miR-409-3p towards coagulation factor 7 (F7) and F2. Of note, all patients had thrombotic events requiring pump change. In conclusion, in HF children, the level of six c-miRNAs involved in the regulation of hemostatic events changed after 30 days of VAD-treatment. In particular, the lowering of c-miR-409-3p regulating both F7 and F2 could reflect a pro-thrombotic state after VAD-implant.
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