siRNA Targeting ECE-1 Partially Reverses Pulmonary Arterial Hypertensionassociated Damage in a Monocrotaline Model

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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Current molecular pharmacology - (2024) vom: 08. März

Sprache:

Englisch

Beteiligte Personen:

Blancas-Napoles, Citlali Margarita [VerfasserIn]
Cabrera-Becerra, Sandra Edith [VerfasserIn]
Sierra-Sánchez, Vivany Maydel [VerfasserIn]
Ocampo-Ortega, Sergio Adrian [VerfasserIn]
Garcia-Rubio, Vanessa Giselle [VerfasserIn]
Romero-Nava, Rodrigo [VerfasserIn]
Huang, Fengyang [VerfasserIn]
Hong, Enrique [VerfasserIn]
Aguilera-Méndez, Asdrúbal [VerfasserIn]
Villafaña, Santiago [VerfasserIn]

Links:

Volltext

Themen:

Endothelin-1
Endothelin-1 converting enzyme
Endothelin-1.
Journal Article
Monocrotaline
Pulmonary arterial hypertension
Small interfering RNA

Anmerkungen:

Date Revised 11.03.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.2174/0118761429283384240226074921

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369551737