Eplerenone suppresses neointimal formation after coronary stent implantation in swine.
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.


CONCLUSIONS
Orally administered eplerenone attenuated collagen accumulation within the neointima, thereby inhibiting neointimal hyperplasia after stent implantation.
Wakabayashi
Kohei
K
Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Kanagawa 227-8501, Japan.
Suzuki
Hiroshi
H
Sato
Takatoshi
T
Iso
Yoshitaka
Y
Katagiri
Takashi
T
Takeyama
Youichi
Y
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D019917:Blood Vessel Prosthesis Implantation; D024042:Collagen Type I / Q000187:drug effects / Q000378:metabolism; D024061:Collagen Type III / Q000187:drug effects / Q000378:metabolism; D023903:Coronary Restenosis / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D004195:Disease Models, Animal; D000077545:Eplerenone; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism; D006965:Hyperplasia / Q000188:drug therapy / Q000378:metabolism; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015607:Stents; D013552:Swine; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism
D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013148:Spironolactone; D000077545:Eplerenone