Title:siRNA Targeting ECE-1 Partially Reverses Pulmonary Arterial Hypertensionassociated
Damage in a Monocrotaline Model
Volume: 17
Author(s): Citlali Margarita Blancas-Napoles, Sandra Edith Cabrera-Becerra, Vivany Maydel Sierra-Sánchez, Sergio Adrian Ocampo-Ortega, Vanessa Giselle Garcia-Rubio, Rodrigo Romero-Nava, Fengyang Huang, Enrique Hong, Asdrúbal Aguilera-Méndez and Santiago Villafaña*
Affiliation:
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México
Keywords:
Pulmonary arterial hypertension, Endothelin-1 converting enzyme, Small interfering RNA, Endothelin-1, Monocrotaline, Endothelin-1.
Abstract:
Aims:
The aim of this study was to develop a possible treatment for pulmonary arterial hypertension.
Background:
Pulmonary arterial hypertension (PAH) is a rare disease characterised by a pulmonary arterial pressure greater than 20 mmHg. One of the factors
that contribute to PAH is an increase in the production of endothelin-1, a polypeptide that increases vascular resistance in the pulmonary arteries,
leading to increased pulmonary arterial pressure and right ventricular hypertrophy.
Objective:
The objective of this study was to design, synthesize, and evaluate two siRNAs directed against endothelin-1 in a rat model of PAH induced with
monocrotaline.
Methods:
Wistar rats were administered monocrotaline (60 mg/kg) to induce a PAH model. Following two weeks of PAH evolution, the siRNAs were
administered, and after two weeks, right ventricular hypertrophy was evaluated using the RV/LV+S ratio, blood pressure, weight, and relative
expression of ECE-1 (Endothelin-converting enzyme-1) mRNA (messenger RNA) by RT-PCR (real-time PCR).
Results:
The monocrotaline group showed an increase in the hypertrophy index and in ECE-1 mRNA, as well as a significant decrease in weight compared
to the control group, while in the monocrotaline + siRNA group, a significant decrease was observed in the relative expression of ECE-1 mRNA,
as well as in right ventricular hypertrophy.
Conclusions:
Based on the above information, we conclude that the administration of siRNAs directed to ECE-1 decreases the damage associated with PAH.
