# Comparative Investigation of the Effects of Entelon150®, Losartan, and Rosuvastatin Following Subdermal Valve Prosthesis in a Rat Model

## TL;DR

This study compares the effects of three drugs on reducing calcification and inflammation in heart valve implants in rats.

## Contribution

The study is the first to compare Entelon150®, losartan, and rosuvastatin in a rat model of bioprosthetic heart valves.

## Key findings

- All three drugs reduced calcium content in heart valve leaflets compared to the control group.
- Entelon150® showed the greatest reduction in inflammatory markers IL-6, OPN, and BMP-2.
- Losartan was most effective in reducing inflammatory cell infiltration.

## Abstract

Background/Objectives: Entelon150® (Vitis vinifera seed extract), losartan, and rosuvastatin have been shown to be effective in reducing calcification and inflammation of bovine pericardium implants. However, no study has compared the effects of the drugs on bioprosthetic heart valve (BHV). This study aimed to compare the anti-calcification and anti-inflammatory effects of each drug in a rat model. Methods: Twenty-eight female Sprague-Dawley rats (two weeks old) were implanted with BHV leaflets in the dorsal subcutis. They were divided into control, losartan (10.3 mg/kg/day), rosuvastatin (2 mg/kg/day), and Entelon150® (30.8 mg/kg/day) groups. Eight weeks later, the calcium level and inflammatory cell infiltration in the BHV leaflets as well as the expression levels of IL-6, osteopontin, and BMP-2 in the surrounding tissues were measured. Results: Losartan-, Entelon150®-, and rosuvastatin-treated groups showed a decrease in the calcium content as compared to the control group in the order. A reduction in the inflammatory cell infiltration was observed in the treatment groups (losartan > Entelon150® > rosuvastatin) as compared to that in the control group. The treatment groups showed a decrease in IL-6, OPN, and BMP-2 expression levels as compared to the control group in the following order: Entelon150® > losartan > rosuvastatin. Conclusions: The calcification of the BHV leaflets and inflammation of the surrounding tissues in treatment groups were lower than those in the control group and were comparable to each other. Entelon150® showed comparable anti-inflammatory and anti-calcification effects and may represent a potential therapeutic candidate for prolonging BHV durability, although further validation is required.