Entelon (vitis vinifera seed extract) reduces degenerative changes in bovine pericardium valve leaflet in a dog intravascular implant model

PLoS One. 2021 Mar 4;16(3):e0235454. doi: 10.1371/journal.pone.0235454. eCollection 2021.

Abstract

Background and aims: Inflammation and calcification are major factors responsible for degeneration of bioprosthetic valve and other substitute heart valve implantations. The objective of this study was to evaluate the anti-inflammatory and anti-calcification effects of Entelon150® (consisting of grape-seed extract) in a beagle dog model of intravascular bovine pericardium implantation.

Methods: In total, 8 healthy male beagle dogs were implanted with a bovine pericardium bilaterally in the external jugular veins and divided into two groups. Animals in the Entelon150® group (n = 4) were treated with 150 mg of Entelon150® twice daily for six weeks after surgery. The negative control (NC) group (n = 4) was treated with 5 ml of saline using the same method. After six weeks, we measured the calcium content, performed histological examination, and performed molecular analysis.

Results: The calcium content of implanted tissue in the Entelon150® group (0.56±0.14 mg/g) was significantly lower than that in the NC group (1.48±0.57 mg/g) (p < 0.05). Histopathological examination showed that infiltration of chronic inflammatory cells, such as fibroblasts and macrophages, occurred around the graft in all groups; however, the inflammation level of the implanted tissue in the Entelon150® group was s lower than that in the NC group. Both immunohistochemical and western blot analyses revealed that bone morphogenetic protein 2 expression was significantly attenuated in the Entelon150® group.

Conclusions: Our results indicate that Entelon150® significantly attenuates post-implantation inflammation and degenerative calcification of the bovine pericardium in dogs. Therefore, Entelon150® may increase the longevity of the bovine pericardium after intravascular implantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Bioprosthesis
  • Calcinosis / drug therapy*
  • Calcinosis / etiology
  • Cattle
  • Dogs
  • Fibroblasts / drug effects
  • Grape Seed Extract / administration & dosage
  • Grape Seed Extract / pharmacology
  • Grape Seed Extract / therapeutic use*
  • Heart Valve Prosthesis
  • Macrophages / drug effects
  • Male
  • Pericardium / transplantation
  • Postoperative Complications / drug therapy*
  • Transcatheter Aortic Valve Replacement / adverse effects
  • Transcatheter Aortic Valve Replacement / methods*

Substances

  • Anti-Inflammatory Agents
  • Grape Seed Extract

Grants and funding

This study was supported by a Korea University Grant (K1924931).