Entelon150? (Vitis vinifera Seed Extract) Attenuates Degenerative Changes in Intravascular Valve Prostheses in Rabbits

Background and Objectives: The therapeutic strategy for inflammation and degenerative calcification is of utmost importance for bioprosthetic heart valve (BHV) implanted patients. The purpose of this study was to compare the anti-inflammatory and anti-calcification effects of Entelon150 (R) (grape seed extract), losartan, and rosuvastatin, in a rabbit model of intravascular BHV leaflet implantation in bovine pericardium. Methods: A total of 28 rabbits were implanted with BHV leaflet in the external jugular veins. The Entelon150 (R) group was administered 7.7 mg/kg Entelon150 (R) twice daily for 6 weeks after surgery. The losartan and rosuvastatin groups received 5.14 mg/kg and 1 mg/kg, respectively, once per day. The control group received 1 ml of saline once daily. And then, calcium concentration was measured in the implanted BHV, and histological and molecular analyses were performed on the surrounding tissues. Results: The calcium content of the implanted tissue in the Entelon150 (R) group (0.013 +/- 0.004 mg/g) was lower than that in the control group (0.066 +/- 0.039 mg/g) (p=0.008). The losartan (0.024 +/- 0.016 mg/g, p=0.032) and rosuvastatin (0.022 +/- 0.011 mg/g, p=0.032) groups had lower calcium content than the control group, and higher tendency than the Entelon150 (R) group. Immunohistochemistry revealed that the expressions of bone morphogenic protein 2 (BMP2), S-100, and angiotensin II type 1 receptor in the Entelon150 (R) group showed lower tendency than those in the control group. The protein expression levels of BMP2 were reduced in the Entelon150 (R) group compared with those in the control group. Conclusions: Entelon150 (R) exhibited a significant effect, similar to other drugs, in reducing calcification and inflammation in the intravascular bovine pericardium.