Angiotensin-Converting Enzyme Inhibitor Reduces Radiation-Induced Periprosthetic Capsular Fibrosis

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-beta 1, MMP-2, and TIMP-2 expression). The alteration of plasma TGF-beta 1 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-beta 1 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-beta 1 positivity, and an increase in MMP-2/TIMP-2 ratio were found significant. In the ramipril + implant + radiation group, the alteration values of TGF-beta 1 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. (C) 2021 Elsevier Inc. All rights reserved.