Prednisolone inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension.
BACKGROUND
Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. There is no therapy that specifically inhibits SMC proliferation. Recent studies reported that prednisolone (PSL) inhibits the postangioplasty proliferation of SMCs in atherosclerotic arteries. In this study, we tested the hypothesis that PSL has antiproliferative effects on pulmonary artery SMCs of patients with IPAH.


RESULTS
Pulmonary artery SMCs were harvested from the pulmonary arteries of 6 patients with IPAH who underwent lung transplantation. Control SMCs were obtained from 5 patients with bronchogenic carcinoma who underwent lung lobectomy. After incubation in the presence of platelet-derived growth factor (PDGF), PSL was added at different concentrations and cell proliferation was assessed by 3H-thymidine incorporation. PSL (2x10(-4) and 2x10(-3) mol/L) significantly inhibited PDGF-stimulated proliferation (P<0.05) of SMCs from patients with IPAH but did not affect cell viability of SMCs, as confirmed by trypan blue staining. In cell cycle analysis using a microscope-based multiparameter laser scanning cytometer, PSL inhibited the progression of SMCs from G(0)/G1 to the S phase. This inhibition was associated with increased p27 expression level. PSL (2x10(-4) mol/L) also inhibited PDGF-induced SMC migration.


CONCLUSIONS
Our results indicate that PSL has an antiproliferative effect on cultured SMCs of pulmonary arteries from patients with IPAH and suggest that PSL may be potentially useful therapeutically in patients with IPAH.
Ogawa
Aiko
A
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan. aiko-oky@umin.ac.jp
Nakamura
Kazufumi
K
Matsubara
Hiromi
H
Fujio
Hideki
H
Ikeda
Tetsuya
T
Kobayashi
Kaoru
K
Miyazaki
Ikuko
I
Asanuma
Masato
M
Miyaji
Katsumasa
K
Miura
Daiji
D
Kusano
Kengo Fukushima
KF
Date
Hiroshi
H
Ohe
Tohru
T
D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D011239:Prednisolone