Title:Repurposing of Angiotensin-converting-enzyme Inhibitor on Prevention of
Post-surgical Tendon Adhesion
Volume: 30
Issue: 11
Author(s): Hamideh Naimi, Majid Khazaei*, Fariba Sharifnia and Sayyed-Hadi Sayyed-Hosseinian
Affiliation:
- Metabolic Syndrome
Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Physiology, Faculty of
Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Keywords:
Achilles tendon adhesion, post-surgical tendon adhesion, renin-angiotensin system, angiotensin-converting-enzyme inhibitor, enalapril, extracellular matrix.
Abstract:
Background: Formation of adhesion bands is a frequent clinical complication after tendon injury or
surgery with limited treatment options. This study investigates the repurposing of Angiotensin-Converting-Enzyme
Inhibitor (ACEI) in attenuating post-operative tendon-sheath adhesion bands in an Achilles tendon rat
model.
Methods: Structural, mechanical, histological, and biochemical characteristics of the Achilles tendons were
compared in the presence and absence of oral ACEI (enalapril) using the Achilles tendon adhesion (TA) model
in rats. Inflammation and total fibrosis of tendon tissues were compared between groups using molecular investigations
along with macroscopic and histological scoring methods.
Results: ACEI significantly alleviated the severity, length, and density of Achilles TAs. Moreover, histopathological
changes, recruitment of inflammatory cells, and inflammation were significantly decreased in post-operative
tissue samples as quantified with the Moran scoring model. We showed that ACEI treatment elicits a
potent anti-fibrotic effect on tendon tissue samples, as illustrated by decreasing the severity and extent of the
formed fibrotic tissue and collagen accumulation at the site of surgery when scored either by Tang or Ishiyama
grading systems. The H&E staining showed no histopathological changes or damage to the principal organs.
Conclusion: Our results showed that ACEI is a safe and effective therapeutic candidate with potent immunomodulatory
and anti-fibrotic features to alleviate surgery-induced development of fibrotic adhesive tissue.
However, its efficacy needs to be further validated in clinical studies.