siRNA Targeting PDE5A Partially Restores Vascular Damage Due to Type 1 Diabetes in a Streptozotocin-Induced Rat Model

Diabetes mellitus is a metabolic disease that can produce different alterations such as endothelial dysfunction, which is defined as a decrease in the vasodilator responses of the mechanisms involved such as the nitric oxide (NO) pathway. The overexpression of PDE5A has been reported in diabetes, wh...

Full description

Saved in:
Bibliographic Details
Published in:Scientia pharmaceutica 2023-11, Vol.91 (4), p.52
Main Authors: Garcia-Rubio, Vanessa Giselle, Cabrera-Becerra, Sandra Edith, Ocampo-Ortega, Sergio Adrian, Blancas-Napoles, Citlali Margarita, Sierra-Sánchez, Vivany Maydel, Romero-Nava, Rodrigo, Gutiérrez-Rojas, Rocío Alejandra, Huang, Fengyang, Hong, Enrique, Villafaña, Santiago
Format: Article
Language:English
Subjects:
Acetylcholine
Blood pressure
Blood vessels
Diabetes
Diabetic neuropathy
Dilatation
Efficiency
endothelial dysfunction
Endothelium
Glucose
Heart rate
Hyperglycemia
Hypertension
Laboratory animals
Nitric oxide
Ostomy
PDE5A mRNA
PDE5A-siRNA
RNA
Rodents
Smooth muscle
Type 1 diabetes
Type 2 diabetes
vasodilation
Vasodilators
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Diabetes mellitus is a metabolic disease that can produce different alterations such as endothelial dysfunction, which is defined as a decrease in the vasodilator responses of the mechanisms involved such as the nitric oxide (NO) pathway. The overexpression of PDE5A has been reported in diabetes, which causes an increase in the hydrolysis of cGMP and a decrease in the NO pathway. For this reason, the aim of this study was to evaluate whether siRNAs targeting PDE5A can reduce the endothelial dysfunction associated with diabetes. We used male Wistar rats (200–250 g) that were administered streptozotocin (STZ) (60 mg/kg i.p) to induce diabetes. Two weeks after STZ administration, the siRNAs or vehicle were administered and then, at 4 weeks, dose–response curves to acetylcholine were performed and PDE5A mRNA levels were measured by RT-PCR. siRNAs were designed by the bioinformatic analysis of human–rat FASTA sequences and synthesised in the Mermade-8 equipment. Our results showed that 4 weeks of diabetes produces a decrease in the vasodilator responses to acetylcholine and an increase in the expression of PDE5A mRNA, while the administration of siRNAs partially restores the vasodilator response and decreases PDE5A expression. We conclude that the administration of siRNAs targeting PDE5A partially reverts the endothelial impairment associated with diabetes.
ISSN:2218-0532
0036-8709
2218-0532
DOI:10.3390/scipharm91040052