Angiotensin-Converting Enzyme Inhibitor Reduces Radiation-Induced Periprosthetic Capsular Fibrosis.
Angiotensin-Converting Enzyme Inhibitors
/ administration & dosage
Animals
Breast
/ pathology
Breast Implantation
/ adverse effects
Breast Implants
/ adverse effects
Breast Neoplasms
/ therapy
Female
Fibrosis
Humans
Implant Capsular Contracture
/ etiology
Male
Mastectomy
/ adverse effects
Radiation Injuries, Experimental
/ etiology
Radiotherapy, Adjuvant
/ adverse effects
Ramipril
/ administration & dosage
Rats
Silicone Gels
/ adverse effects
ACE inhibitor
Contracture
Fibrosis
Radiation
Ramipril
Silicone capsule
Journal
The Journal of surgical research
ISSN: 1095-8673
Titre abrégé: J Surg Res
Pays: United States
ID NLM: 0376340
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
11
06
2020
revised:
12
01
2021
accepted:
31
01
2021
pubmed:
6
3
2021
medline:
22
9
2021
entrez:
5
3
2021
Statut:
ppublish
Résumé
The capsular contracture is one of the main complications after radiotherapy in patients with implant-based reconstruction. The aim of this study is to evaluate the efficacy of ramipril for the prevention of radiation-induced fibrosis around the silicone implant. Thirty Wistar rats in 5 groups were used. Group 1: implant; group 2: implant + radiation; group 3: ramipril + implant; group 4: ramipril + implant + radiation; group 5: sham. Ramipril treatment was started 5 d before surgery and continued for 12 wk after surgery. A mini silicone implant was placed in the back of the rats. A single fraction of 21.5 Gy radiation was applied. Tissues were examined histologically and immunohistochemically (TGF-β1, MMP-2, and TIMP-2 expression). The alteration of plasma TGF-β1 levels was examined before and after the experiment. After applying implant or implant + radiation, capsular thickness, percentage of fibrotic area, tissue and plasma TGF-β1 levels significantly increased, and MMP-2/TIMP-2 ratio significantly decreased compared with the sham group. In ramipril-treated groups, the decrease in capsular thickness, fibrosis, TGF-β1 positivity, and an increase in MMP-2/TIMP-2 ratio were found significant. In the ramipril + implant + radiation group, the alteration values of TGF-β1 dramatically decreased. Our results show that ramipril reduces radiation-induced fibrosis and contracture. The results of our study may be important for the design of the clinical trials required to investigate the effective and safe doses of ramipril, which is an inexpensive and easily tolerated drug, on humans.
Sections du résumé
BACKGROUND
The capsular contracture is one of the main complications after radiotherapy in patients with implant-based reconstruction. The aim of this study is to evaluate the efficacy of ramipril for the prevention of radiation-induced fibrosis around the silicone implant.
MATERIALS AND METHODS
Thirty Wistar rats in 5 groups were used. Group 1: implant; group 2: implant + radiation; group 3: ramipril + implant; group 4: ramipril + implant + radiation; group 5: sham. Ramipril treatment was started 5 d before surgery and continued for 12 wk after surgery. A mini silicone implant was placed in the back of the rats. A single fraction of 21.5 Gy radiation was applied. Tissues were examined histologically and immunohistochemically (TGF-β1, MMP-2, and TIMP-2 expression). The alteration of plasma TGF-β1 levels was examined before and after the experiment.
RESULTS
After applying implant or implant + radiation, capsular thickness, percentage of fibrotic area, tissue and plasma TGF-β1 levels significantly increased, and MMP-2/TIMP-2 ratio significantly decreased compared with the sham group. In ramipril-treated groups, the decrease in capsular thickness, fibrosis, TGF-β1 positivity, and an increase in MMP-2/TIMP-2 ratio were found significant. In the ramipril + implant + radiation group, the alteration values of TGF-β1 dramatically decreased.
CONCLUSIONS
Our results show that ramipril reduces radiation-induced fibrosis and contracture. The results of our study may be important for the design of the clinical trials required to investigate the effective and safe doses of ramipril, which is an inexpensive and easily tolerated drug, on humans.
Identifiants
pubmed: 33667872
pii: S0022-4804(21)00069-X
doi: 10.1016/j.jss.2021.01.033
pii:
doi:
Substances chimiques
Angiotensin-Converting Enzyme Inhibitors
0
Silicone Gels
0
Ramipril
L35JN3I7SJ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
167-175Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.