Eplerenone suppresses neointimal formation after coronary stent implantation in swine

Int J Cardiol. 2006 Feb 15;107(2):260-6. doi: 10.1016/j.ijcard.2005.03.078. Epub 2005 Jul 14.

Abstract

Background: Enhanced extracellular matrix accumulation rather than cell proliferation contributes to later stages of in-stent restenosis. Aldosterone itself has been shown to increase cardiovascular fibrosis, therefore, we studied the suppressive effects of eplerenone, a new aldosterone receptor antagonist, on neointimal hyperplasia after coronary stent implantation in swine.

Methods: Palmatz-Shatz stents were implanted in the left anterior descending artery of 36 pigs. One hundred milligrams of Eplerenone was orally administered from 1 week before, to 4 weeks after stent implantation in Group E (n=18), and vehicle was given to Group C (n=18). Pigs were sacrificed 1 or 4 weeks after stent implantation. The number of infiltrating macrophages was calculated at 1 week. Morphometrical analysis was performed to measure the area of each layer, and %area of fibrosis and mRNA for collagen I, III and TGF-beta was analyzed by RT-PCR at 4 weeks.

Results: The number of infiltrating macrophages was less in Group E than in Group C (p<0.01). The overall size of coronary arteries at 4 weeks was similar in both groups. However, the luminal area was larger in Group E than in Group C (p<0.05), and the intimal area was smaller in Group E than in Group C (p<0.05). The %area of fibrosis was significantly less in Group E than in Group C at 4 weeks (p<0.01). In Group E, the expression of mRNA for collagen I, III and TGF-beta was significantly reduced.

Conclusion: Orally administered eplerenone attenuated collagen accumulation within the neointima, thereby inhibiting neointimal hyperplasia after stent implantation.

Publication types

  • Comparative Study

MeSH terms

  • Actins / drug effects
  • Actins / metabolism
  • Administration, Oral
  • Animals
  • Blood Vessel Prosthesis Implantation
  • Collagen Type I / drug effects
  • Collagen Type I / metabolism
  • Collagen Type III / drug effects
  • Collagen Type III / metabolism
  • Coronary Restenosis / prevention & control*
  • Coronary Vessels / drug effects*
  • Coronary Vessels / metabolism
  • Coronary Vessels / surgery
  • Disease Models, Animal
  • Eplerenone
  • Fibrosis / drug therapy
  • Fibrosis / metabolism
  • Hyperplasia / drug therapy
  • Hyperplasia / metabolism
  • Immunohistochemistry
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mineralocorticoid Receptor Antagonists
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spironolactone / administration & dosage
  • Spironolactone / analogs & derivatives*
  • Spironolactone / pharmacology
  • Stents*
  • Swine
  • Time Factors
  • Transforming Growth Factor beta / drug effects
  • Transforming Growth Factor beta / metabolism
  • Tunica Intima / drug effects*
  • Tunica Intima / metabolism

Substances

  • Actins
  • Collagen Type I
  • Collagen Type III
  • Mineralocorticoid Receptor Antagonists
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Spironolactone
  • Eplerenone